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Sample records for genotoxic effects induced

  1. Protective effect of curcumin against formaldehyde-induced genotoxicity in A549 Cell Lines.

    PubMed

    Zhang, Ben-Yan; Shi, Yu-Qin; Chen, Xin; Dai, Juan; Jiang, Zhong-Fa; Li, Ning; Zhang, Zhi-Bing

    2013-12-01

    Formaldehyde is ubiquitous in the environment. It is known to be a genotoxic substance. We hypothesized that reactive oxygen species (ROS) and lipid peroxidation are involved in formaldehyde-induced genotoxicity in human lung cancer cell lines A549. To test this hypothesis, we investigated the effects of antioxidant on formaldehyde-induced genotoxicity in A549 Cell Lines. Formaldehyde exposure caused induction of DNA-protein cross-links (DPCs). Curcumin is an important antioxidant. Formaldehyde significantly increased malondialdehyde (MDA) levels, and decreased superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity. In addition, the activation of NF-κB and AP-1 were induced by formaldehyde treatment. Pretreatment with curcumin counteracted formaldehyde-induced oxidative stress, ameliorated DPCs and attenuated activation of NF-κB and AP-1 in A549 Cell Lines. These results, taken together, suggest that formaldehyde induced genotoxicity through its ROS and lipid peroxidase activity and caused DPCs effects in A549 cells.

  2. Modulatory Effect of Betulinic Acid on the Genotoxicity Induced by Different Mutagens in V79 Cells

    PubMed Central

    Acésio, Nathália Oliveira; de Oliveira, Pollyanna Francielli; Mastrocola, Daiane Fernanda Pereira; Lima, Ildercílio Mota de Souza; Munari, Carla Carolina; Sato, Vânia Luiza Ferreira Lucatti; Souza, Andressa Aparecida Silva; Flauzino, Lúzio Gabriel Bocalon; Cunha, Wilson Roberto; Tavares, Denise Crispim

    2016-01-01

    Betulinic acid (BA) is a pentacyclic triterpene that can be isolated from many medicinal plants around the world. The aim of this study was to evaluate the genotoxic potential of BA and its effect on the genotoxicity induced by different mutagens in V79 cells using the cytokinesis-block micronucleus assay. Different BA concentrations were combined with methyl methanesulfonate (MMS), doxorubicin (DXR), camptothecin (CPT), and etoposide (VP-16). The frequencies of micronuclei in cultures treated with different BA concentrations did not differ from those of the negative control. Treatment with BA and MMS resulted in lower micronucleus frequencies than those observed for cultures treated with MMS alone. On the other hand, a significant increase in micronucleus frequencies was observed in cultures treated with BA combined with DXR or VP-16 when compared to these mutagens alone. The results showed no effect of BA on CPT-induced genotoxicity. Therefore, BA was not genotoxic under the present experimental conditions and exerted a different influence on the genotoxicity induced by different mutagens. The modulatory effect of BA depends on the type of mutagen and concentrations used. PMID:27195016

  3. Protective Effects of Quercetin against Dimethoate-Induced Cytotoxicity and Genotoxicity in Allium sativum Test

    PubMed Central

    Ahmad, Waseem; Shaikh, Sibhghatulla; Nazam, Nazia; Lone, Mohammad Iqbal

    2014-01-01

    The present investigation was directed to study the possible protective activity of quercetin—a natural antioxidant against dimethoate-induced cyto- and genotoxicity in meristematic cells of Allium sativum. So far there is no report on the biological properties of quercetin in plant test systems. Chromosome breaks, multipolar anaphase, stick chromosome, and mitotic activity were undertaken in the current study as markers of cyto- and genotoxicity. Untreated control, quercetin controls (@ 5, 10 and 20 μg/mL for 3 h), and dimethoate exposed groups (@ 100 and 200 μg/mL for 3 h) were maintained. For protection against cytogenotoxicity, the root tip cells treated with dimethoate at 100 and 200 μg/mL for 3 h and quercetin treatment at 5, 10, and 20 μg/mL for 16 h, prior to dimethoate treatment, were undertaken. Quercetin was found to be neither cytotoxic nor genotoxic in Allium sativum control at these doses. A significant increase (P < 0.05) in chromosomal aberrations was noted in dimethoate treated Allium. Pretreatment of Allium sativum with quercetin significantly (P < 0.05) reduced dimethoate-induced genotoxicity and cytotoxicity in meristematic cells, and these effects were dose dependent. In conclusion, quercetin has a protective role in the abatement of dimethoate-induced cyto- and genotoxicity in the meristematic cells of Allium sativum that resides, at least in part, on its antioxidant effects. PMID:27379342

  4. THE EFFECTS OF HEAT SHOCK PROTEIN 70 (HSP70) AND EXPOSURE PROTOCOL ON ARSENITE INDUCED GENOTOXICITY

    EPA Science Inventory

    The Effects of Heat Shock Protein 70 (Hsp70) and Exposure Protocol on Arsenite Induced Genotoxicity

    Barnes, J.A.1,2, Collins, B.W.2, Dix, D.J.3 and Allen J.W2.
    1National Research Council, 2Environmental Carcinogenesis Division, 3Reproductive Toxicology Division, Office...

  5. EFFECT OF EXPOSURE PROTOCOL AND HEAT SHOCK PROTEIN EXPRESSION ON ARSENITE INDUCED GENOTOXICITY IN MCF-7 BREAST CANCER CELLS

    EPA Science Inventory


    Effect of exposure protocol and heat shock protein expression on arsenite induced genotoxicity in MCF-7 breast cancer cells

    The genotoxic effects of arsenic (As) are well accepted, yet its mechanism of action is not clearly defined. Heat-shock proteins (HSPs) protect...

  6. Protective effect of boric acid on lead- and cadmium-induced genotoxicity in V79 cells.

    PubMed

    Ustündağ, Aylin; Behm, Claudia; Föllmann, Wolfram; Duydu, Yalçin; Degen, Gisela H

    2014-06-01

    The toxic heavy metals cadmium (Cd) and lead (Pb) are important environmental pollutants which can cause serious damage to human health. As the metal ions (Cd(2+) and Pb(2+)) accumulate in the organism, there is special concern regarding chronic toxicity and damage to the genetic material. Metal-induced genotoxicity has been attributed to indirect mechanisms, such as induction of oxidative stress and interference with DNA repair. Boron is a naturally occurring element and considered to be an essential micronutrient, although the cellular activities of boron compounds remain largely unexplored. The present study has been conducted to evaluate potential protective effects of boric acid (BA) against genotoxicity induced by cadmium chloride (CdCl2) and lead chloride (PbCl2) in V79 cell cultures. Cytotoxicity assays (neutral red uptake and cell titer blue assay) served to determine suitable concentrations for subsequent genotoxicity assays. Chromosomal damage and DNA strand breaks were assessed by micronucleus tests and comet assays. Both PbCl2 and CdCl2 (at 3, 5 and 10 µM) were shown to induce concentration-dependent increases in micronucleus frequencies and DNA strand breaks in V79 cells. BA itself was not cytotoxic (up to 300 µM) and showed no genotoxic effects. Pretreatment of cells with low levels of BA (2.5 and 10 µM) was found to strongly reduce the genotoxic effects of the tested metals. Based on the findings of this in vitro study, it can be suggested that boron provides an efficient protection against the induction of DNA strand breaks and micronuclei by lead and cadmium. Further studies on the underlying mechanisms for the protective effect of boron are needed.

  7. Protective effect of bixin on cisplatin-induced genotoxicity in PC12 cells.

    PubMed

    Dos Santos, Graciela Cristina; Mendonça, Leonardo Meneghin; Antonucci, Gilmara Ausech; Dos Santos, Antonio Cardozo; Antunes, Lusânia Maria Greggi; Bianchi, Maria de Lourdes Pires

    2012-02-01

    Bixin is the main carotenoid found in annatto seeds (Bixa orellana L.) and is responsible for their reddish-orange color. The antioxidant properties of this compound are associated with its ability to scavenge free radicals, which may reduce damage and protect tissues against toxicity caused by anticancer drugs such as cisplatin. In this study, the genotoxicity and antigenotoxicity of bixin on cisplatin-induced toxicity in PC12 cells was assessed. Cytotoxicity was evaluated using the MTT assay, mutagenicity, genotoxicity, and protective effect of bixin were evaluated using the micronucleus test and comet assay. PC12 cells were treated with bixin (0.05, 0.08, and 0.10μg/mL), cisplatin (0.1μg/mL) or a combination of both bixin and cisplatin. Bixin was neither cytotoxic nor genotoxic compared to the controls. In the combined treatment bixin significantly reduced the percentage of DNA in tail and the frequency of micronuclei induced by cisplatin. This result suggests that bixin can function as a protective agent, reducing cisplatin-induced DNA damage in PC12 cells, and it is possible that this protection could also extend to neuronal cells. Further studies are being conducted to better understand the mechanisms involved in the activity of this protective agent prior to using it therapeutically. PMID:22019694

  8. Flurochloridone-based herbicides induced genotoxicity effects on Rhinella arenarum tadpoles (Anura: Bufonidae).

    PubMed

    Nikoloff, Noelia; Natale, Guillermo S; Marino, Damián; Soloneski, Sonia; Larramendy, Marcelo L

    2014-02-01

    Acute toxicity and genotoxicity of the flurochloridone (FLC)-containing commercial formulation herbicides Twin Pack Gold(®) (25 percent a.i.) and Rainbow(®) (25 percent a.i.) were evaluated on Rhinella arenarum (Anura: Bufonidae) tadpoles exposed under laboratory conditions. Lethal effect was evaluated as end point for lethality, whereas frequency of micronuclei (MN) and single cell gel electrophoresis (SCGE) were employed as end points for genotoxicity. Lethality studies revealed equivalent LC-5096 h values of 2.96 and 2.85 mg/L for Twin Pack Gold(®) and Rainbow(®), respectively. Twin Pack Gold(®) did not induce DNA damage at the chromosomal level, whereas Rainbow(®) increased the frequency of MN only when the lowest concentration (0.71 mg/L) was used. However, all concentrations of Twin Pack Gold(®) and Rainbow(®) increased the frequencies of primary DNA lesions estimated by alkaline SCGE. This study represents the first evidence of the acute toxic and genotoxic effects exerted by two FLC-based commercial formulations, Twin Pack Gold(®) and Rainbow(®), on tadpoles of an amphibian species native to Argentina under laboratory conditions. Finally, our findings highlight the importance of minimizing the impacts on nontarget living species exposed to agrochemicals.

  9. Protective effects of vitamin E against atrazine-induced genotoxicity in rats.

    PubMed

    Singh, Mohan; Kaur, Pushpindar; Sandhir, Rajat; Kiran, Ravi

    2008-07-31

    Atrazine (2-chloro-4-(ethylamino)-6-(isopropylamino)-s-triazine) is one of the most commonly used herbicides to control grasses and weeds. The widespread contamination and persistence of atrazine residues in the environment has resulted in human exposure. Vitamin E is a primary antioxidant that plays an important role in protecting cells against toxicity by inactivating free radicals generated following pesticides exposure. The present study was undertaken to investigate the protective effect of vitamin E against atrazine-induced genotoxicity. Three different methods: gel electrophoresis, comet assay and micronucleus test were used to assess the atrazine-induced genotoxicity and to evaluate the protective effects of vitamin E. Atrazine was administered to male rats at a dose of 300 mg/kg body weight for a period of 7, 14 and 21 days. There was a significant increase (P<0.001) in tail length of comets from blood and liver cells treated with atrazine as compared to controls. Co-administration of vitamin E (100 mg/kg body weight) along with atrazine resulted in decrease in tail length of comets as compared to the group treated with atrazine alone. Micronucleus assay revealed a significant increase (P<0.001) in the frequency of micronucleated cells (MNCs) following atrazine administration. In the animals administrated vitamin E along with atrazine there was a significant decrease in percentage of micronuclei as compared to atrazine treated rats. The increase in frequency of micronuclei in liver cells and tail length of comets confirm genotoxicity induced by atrazine in blood and liver cells. In addition, the findings clearly demonstrate protective effect of vitamin E in attenuating atrazine-induced DNA damage. PMID:18582598

  10. Protective Effect of Onion Extract on Bleomycin-Induced Cytotoxicity and Genotoxicity in Human Lymphocytes

    PubMed Central

    Cho, Yoon Hee; Lee, Joong Won; Woo, Hae Dong; Lee, Sunyeong; Kim, Yang Jee; Lee, Younghyun; Shin, Sangah; Joung, Hyojee; Chung, Hai Won

    2016-01-01

    Following one of the world’s largest nuclear accidents, occured at Fukushima, Japan in 2011, a significant scientific effort has focused on minimizing the potential adverse health effects due to radiation exposure. The use of natural dietary antioxidants to reduce the risk of radiation-induced oxidative DNA damage is a simple strategy for minimizing radiation-related cancer rates and improving overall health. The onion is among the richest sources of dietary flavonoids and is an important food for increasing their overall intake. Therefore, we examined the effect of an onion extract on cyto- and geno-toxicity in human lymphocytes treated with bleomycin (BLM), a radiomimetic agent. In addition, we measured the frequency of micronuclei (MN) and DNA damage following treatment with BLM using a cytokinesis-blocked micronucleus assay and a single cell gel electrophoresis assay. We observed a significant increase in cell viability in lymphocytes treated with onion extract then exposed to BLM compared to cells treated with BLM alone. The frequency of BLM induced MN and DNA damage increased in a dose-dependent manner; however, when lymphocytes were pretreated with onion extract (10 and 20 μL/mL), the frequency of BLM-induced MN was decreased at all doses of BLM and DNA damage was decreased at 3 μg/mL of BLM. These results suggest that onion extract may have protective effects against BLM-induced cyto- and genotoxicity in human lymphocytes. PMID:26907305

  11. Protective Effect of Onion Extract on Bleomycin-Induced Cytotoxicity and Genotoxicity in Human Lymphocytes.

    PubMed

    Cho, Yoon Hee; Lee, Joong Won; Woo, Hae Dong; Lee, Sunyeong; Kim, Yang Jee; Lee, Younghyun; Shin, Sangah; Joung, Hyojee; Chung, Hai Won

    2016-02-19

    Following one of the world's largest nuclear accidents, occured at Fukushima, Japan in 2011, a significant scientific effort has focused on minimizing the potential adverse health effects due to radiation exposure. The use of natural dietary antioxidants to reduce the risk of radiation-induced oxidative DNA damage is a simple strategy for minimizing radiation-related cancer rates and improving overall health. The onion is among the richest sources of dietary flavonoids and is an important food for increasing their overall intake. Therefore, we examined the effect of an onion extract on cyto- and geno-toxicity in human lymphocytes treated with bleomycin (BLM), a radiomimetic agent. In addition, we measured the frequency of micronuclei (MN) and DNA damage following treatment with BLM using a cytokinesis-blocked micronucleus assay and a single cell gel electrophoresis assay. We observed a significant increase in cell viability in lymphocytes treated with onion extract then exposed to BLM compared to cells treated with BLM alone. The frequency of BLM induced MN and DNA damage increased in a dose-dependent manner; however, when lymphocytes were pretreated with onion extract (10 and 20 μL/mL), the frequency of BLM-induced MN was decreased at all doses of BLM and DNA damage was decreased at 3 μg/mL of BLM. These results suggest that onion extract may have protective effects against BLM-induced cyto- and genotoxicity in human lymphocytes.

  12. Protective effects of boron on cyclophosphamide induced lipid peroxidation and genotoxicity in rats.

    PubMed

    Ince, Sinan; Kucukkurt, Ismail; Demirel, Hasan Huseyin; Acaroz, Damla Arslan; Akbel, Erten; Cigerci, Ibrahim Hakki

    2014-08-01

    The aim of the present study was to evaluate the possible protective effect of boron (B) on cyclophosphamide (CYC) induced oxidative stress in rats. Totally, thirty Wistar albino male rats were fed standard rodent diet and divided into 5 equal groups: physiological saline was given intraperitoneally (i.p.) to the control group (vehicle treated), to the second group only 75 mg kg(-1) CYC was given i.p. on the 14th d, and boron was administered (5, 10, and 20 mg kg(-1), i.p.) to the other groups for 14 d and CYC (75 mg kg(-1), i.p.) on the 14th d. CYC caused increase of malondialdehyde and decrease of glutathione levels, decrease of superoxide dismutase activities in erythrocyte and tissues, decrease of erythrocyte, heart, lung, and brain catalase, and plasma antioxidant activities. Also, CYC treatment caused to DNA damage in mononuclear leukocytes. Moreover, B exhibited protective action against the CYC-induced histopathological changes in tissues. However, treatment of B decreased severity of CYC-induced lipid peroxidation and genotoxicity on tissues. In conclusion, B has ameliorative effects against CYC-induced lipid peroxidation and genotoxicity by enhancing antioxidant defence mechanism in rat.

  13. Radioprotective effect of chicory seeds against genotoxicity induced by ionizing radiation in human normal lymphocytes.

    PubMed

    Hosseinimehr, S J; Ghaffari-Rad, V; Rostamnezhad, M; Ghasemi, A; Allahverdi Pourfallah, T; Shahani, S

    2015-01-01

    The search for less-toxic radioprotective agents has led to a growing trend towards natural products. Protective effect of the methanolic extract of chicory seeds (MCS) was investigated against genotoxicity induced by ionizing radiation in human lymphocytes. Human peripheral blood samples were collected and incubated with MCS at different concentrations (10, 50, 100, and 200 μg/mL) for two hours. The whole blood samples were exposed in vitro to X-ray at dose 2.5 Gy. Then, the lymphocytes were cultured with mitogenic stimulation to determine the micronucleus in cytokinesis blocked binucleated cell. The methanolic extract at all doses significantly reduced the frequency of micronuclei in binucleated lymphocytes, as compared with similarly irradiated lymphocytes without any extract treatment. The maximum protection was observed at 200 μg/mL of MCS, it completely protected genotoxicity induced by ionizing radiation in human lymphocytes. The extract exhibited a concentration-dependent radical scavenging activity on 1,1-diphenyl-2-picryl hydrazyl free radicals. HPLC analysis of MCS showed this extract is containing chlorogenic acid as a phenolic compound. These data suggest that the radioprotective effect of methanolic extract of chicory seeds can be attributed to the presence of phenolic compounds such as chlorogenic acid which act as antioxidant agents. PMID:26278267

  14. Protective effects of acerola juice on genotoxicity induced by iron in vivo.

    PubMed

    Horta, Roberta Nunes; Kahl, Vivian Francilia Silva; Sarmento, Merielen da Silva; Nunes, Marisa Fernanda Silva; Porto, Carem Rejane Maglione; Andrade, Vanessa Moraes de; Ferraz, Alexandre de Barros Falcão; Silva, Juliana Da

    2016-03-01

    Metal ions such as iron can induce DNA damage by inducing reactive oxygen species (ROS) and oxidative stress. Vitamin C is one of the most widely consumed antioxidants worldwide, present in many fruits and vegetables, especially inMalpighia glabra L., popularly known as acerola, native to Brazil. Acerola is considered a functional fruit due to its high antioxidant properties and phenolic contents, and therefore is consumed to prevent diseases or as adjuvant in treatment strategies. Here, the influence of ripe and unripe acerola juices on iron genotoxicity was analyzed in vivo using the comet assay and micronucleus test. The comet assay results showed that acerola juice exerted no genotoxic or antigenotoxic activity. Neither ripe nor unripe acerola juices were mutagenic to animals treated with juices, in micronucleus test. However, when compared to iron group, the pre-treatment with acerola juices exerted antimutagenic activity, decreasing significantly micronucleus mean values in bone marrow. Stage of ripeness did not influence the interaction of acerola compounds with DNA, and both ripe and unripe acerola juices exerted protective effect over DNA damage generated by iron.

  15. Protective effects of acerola juice on genotoxicity induced by iron in vivo

    PubMed Central

    Horta, Roberta Nunes; Kahl, Vivian Francilia Silva; Sarmento, Merielen da Silva; Nunes, Marisa Fernanda Silva; Porto, Carem Rejane Maglione; de Andrade, Vanessa Moraes; Ferraz, Alexandre de Barros Falcão; Silva, Juliana Da

    2016-01-01

    Abstract Metal ions such as iron can induce DNA damage by inducing reactive oxygen species (ROS) and oxidative stress. Vitamin C is one of the most widely consumed antioxidants worldwide, present in many fruits and vegetables, especially inMalpighia glabra L., popularly known as acerola, native to Brazil. Acerola is considered a functional fruit due to its high antioxidant properties and phenolic contents, and therefore is consumed to prevent diseases or as adjuvant in treatment strategies. Here, the influence of ripe and unripe acerola juices on iron genotoxicity was analyzed in vivo using the comet assay and micronucleus test. The comet assay results showed that acerola juice exerted no genotoxic or antigenotoxic activity. Neither ripe nor unripe acerola juices were mutagenic to animals treated with juices, in micronucleus test. However, when compared to iron group, the pre-treatment with acerola juices exerted antimutagenic activity, decreasing significantly micronucleus mean values in bone marrow. Stage of ripeness did not influence the interaction of acerola compounds with DNA, and both ripe and unripe acerola juices exerted protective effect over DNA damage generated by iron. PMID:27007905

  16. Protective effects of acerola juice on genotoxicity induced by iron in vivo.

    PubMed

    Horta, Roberta Nunes; Kahl, Vivian Francilia Silva; Sarmento, Merielen da Silva; Nunes, Marisa Fernanda Silva; Porto, Carem Rejane Maglione; Andrade, Vanessa Moraes de; Ferraz, Alexandre de Barros Falcão; Silva, Juliana Da

    2016-03-01

    Metal ions such as iron can induce DNA damage by inducing reactive oxygen species (ROS) and oxidative stress. Vitamin C is one of the most widely consumed antioxidants worldwide, present in many fruits and vegetables, especially inMalpighia glabra L., popularly known as acerola, native to Brazil. Acerola is considered a functional fruit due to its high antioxidant properties and phenolic contents, and therefore is consumed to prevent diseases or as adjuvant in treatment strategies. Here, the influence of ripe and unripe acerola juices on iron genotoxicity was analyzed in vivo using the comet assay and micronucleus test. The comet assay results showed that acerola juice exerted no genotoxic or antigenotoxic activity. Neither ripe nor unripe acerola juices were mutagenic to animals treated with juices, in micronucleus test. However, when compared to iron group, the pre-treatment with acerola juices exerted antimutagenic activity, decreasing significantly micronucleus mean values in bone marrow. Stage of ripeness did not influence the interaction of acerola compounds with DNA, and both ripe and unripe acerola juices exerted protective effect over DNA damage generated by iron. PMID:27007905

  17. The protective effect of aloe vera juice on lindane induced hepatotoxicity and genotoxicity.

    PubMed

    Etim, O E; Farombi, E O; Usoh, I F; Akpan, E J

    2006-10-01

    The protective effect of fresh aloe vera (AV) leaves extract on lindane (LD) - induced hepatoxicity and genotoxicity was studied. Serum levels of hepatic enzyme markers: glutamate pyruvate transaminase (GPT), glutamate oxaloacetate transaminase (GOT), gamma glutamyl transferase (GGT) and alkaline phosphatase (ALP) were determined after oral administration of aloe vera leaves extract and lindane. The level of polychromatic erythrocytes was also observed. Pretreatment with aloe vera leaves extract at concentration of 1.0 ml/kg body weight significantly decreased (P<0.05) the serum levels of GPT (by 41.8%), GOT (by 36.5%), GGT (by 14.3%) and ALP (by 10.7%) induced by 100mg/kg body weight of lindane. The level of polychromatic erythrocytes observed was not statistically significant when compared to control.

  18. The genotoxic effects of DNA lesions induced by artificial UV-radiation and sunlight.

    PubMed

    Schuch, André Passaglia; Menck, Carlos Frederico Martins

    2010-06-01

    Solar radiation sustains and affects all life forms on Earth. The increase in solar UV-radiation at environmental levels, due to depletion of the stratospheric ozone layer, highlights serious issues of social concern. This becomes still more dramatic in tropical and subtropical regions where radiation-intensity is still higher. Thus, there is the need to evaluate the harmful effects of solar UV-radiation on the DNA molecule as a basis for assessing the risks involved for human health, biological productivity and ecosystems. In order to evaluate the profile of DNA damage induced by this form of radiation and its genotoxic effects, plasmid DNA samples were exposed to artificial-UV lamps and directly to sunlight. The induction of cyclobutane pyrimidine dimer photoproducts (CPDs) and oxidative DNA damage in these molecules were evaluated by means of specific DNA repair enzymes. On the other hand, the biological effects of such lesions were determined through the analysis of the DNA inactivation rate and mutation frequency, after replication of the damaged pCMUT vector in an Escherichia coliMBL50 strain. The results indicated the induction of a significant number of CPDs after exposure to increasing doses of UVC, UVB, UVA radiation and sunlight. Interestingly, these photoproducts are those lesions that better correlate with plasmid inactivation as well as mutagenesis, and the oxidative DNA damages induced present very low correlation with these effects. The results indicated that DNA photoproducts play the main role in the induction of genotoxic effects by artificial UV-radiation sources and sunlight.

  19. EFFECTS OF HEAT SHOCK PROTEIN 70 (HSP70) ON ARSENITE INDUCED GENOTOXICITY

    EPA Science Inventory

    Arsenic (As), a human carcinogen, is known to be genotoxic although its mechanism(s) of action for tumorigenesis is not well understood. Among the toxicity-related properties of this chemical are its clastogenic and aneugenic activities, as well as its capacity for inducing stres...

  20. Nickel oxide nanoparticles induce inflammation and genotoxic effect in lung epithelial cells.

    PubMed

    Capasso, Laura; Camatini, Marina; Gualtieri, Maurizio

    2014-04-01

    Nickel oxide nanoparticles (NiONPs) toxicity has been evaluated in the human pulmonary epithelial cell lines: BEAS-2B and A549. The nanoparticles, used at the doses of 20, 40, 60, 80, 100 μg/ml, induced a significant reduction of cell viability and an increase of apoptotic and necrotic cells at 24h. A significant release of interleukin-6 and -8 was assessed after 24h of treatment, even intracellular ROS increased already at 45 min after exposure. The results obtained evidenced that the cytokines release was dependent on mitogen activated protein kinases (MAPK) cascade through the induction of NF-kB pathway. NiONPs induced cell cycle alteration in both the cell lines even in different phases and these modifications may be induced by the NPs genotoxic effect, suggested by the nuclear translocation of phospho-ATM and phospho-ATR. Our results confirm the cytotoxic and pro-inflammatory potential of NiONPs. Moreover their ability in inducing DNA damage responses has been demonstrated. Such effects were present in A549 cells which internalize the NPs and BEAS-2B cells in which endocytosis has not been observed. PMID:24503009

  1. Natural Antioxidants Against Arsenic-Induced Genotoxicity.

    PubMed

    Kumar, Munesh; Lalit, Minakshi; Thakur, Rajesh

    2016-03-01

    Arsenic is present in water, soil, and air in organic as well as in inorganic forms. However, inorganic arsenic is more toxic than organic and can cause many diseases including cancers in humans. Its genotoxic effect is considered as one of its carcinogenic actions. Arsenic can cause DNA strand breaks, deletion mutations, micronuclei formation, DNA-protein cross-linking, sister chromatid exchange, and DNA repair inhibition. Evidences indicate that arsenic causes DNA damage by generation of reactive free radicals. Nutritional supplementation of antioxidants has been proven highly beneficial against arsenic genotoxicity in experimental animals. Recent studies suggest that antioxidants protect mainly by reducing excess free radicals via restoring the activities of cellular enzymatic as well as non-enzymatic antioxidants and decreasing the oxidation processes such as lipid peroxidation and protein oxidation. The purpose of this review is to summarize the recent literature on arsenic-induced genotoxicity and its mitigation by naturally derived antioxidants in various biological systems.

  2. Arsenic-induced biochemical and genotoxic effects and distribution in tissues of Sprague-Dawley rats

    PubMed Central

    Patlolla, Anita K.; Todorov, Todor I.; Tchounwou, Paul B.; van der Voet, Gijsbert; Centeno, Jose A.

    2012-01-01

    Arsenic (As) is a well documented human carcinogen. However, its mechanisms of toxic action and carcinogenic potential in animals have not been conclusive. In this research, we investigated the biochemical and genotoxic effects of As and studied its distribution in selected tissues of Sprague-Dawley rats. Four groups of six male rats, each weighing approximately 60 ± 2 g, were injected intraperitoneally, once a day for 5 days with doses of 5, 10, 15, 20 mg/kg bw of arsenic trioxide. A control group was also made of 6 animals injected with distilled water. Following anaesthetization, blood was collected and enzyme analysis was performed by spectrophotometry following standard protocols. At the end of experimentation, the animals were sacrificed, and the lung, liver, brain and kidney were collected 24 h after the fifth day treatment. Chromosome and micronuclei preparation was obtained from bone marrow cells. Arsenic exposure significantly increased (p<0.05) the activities of plasma alanine aminotransferase-glutamate pyruvate transaminase (ALT/GPT), and aspartate aminotransferase-glutamate oxaloacetate transaminase (AST/GOT), as well as the number of structural chromosomal aberrations (SCA) and frequency of micronuclei (MN) in the bone marrow cells. In contrast, the mitotic index in these cells was significantly reduced (p<0.05). These findings indicate that aminotransferases are candidate biomarkers for arsenic-induced hepatotoxicity. Our results also demonstrate that As has a strong genotoxic potential, as measured by the bone marrow SCA and MN tests in Sprague-Dawley rats. Total arsenic concentrations in tissues were measured by inductively coupled plasma mass spectrometry (ICP-MS). A dynamic reaction cell (DRC) with hydrogen gas was used to eliminate the ArCl interference at mass 75, in the measurement of total As. Total As doses in tissues tended to correlate with specific exposure levels. PMID:23175155

  3. Radioprotective effect of mefenamic acid against radiation-induced genotoxicity in human lymphocytes

    PubMed Central

    Nobakht, Reyhaneh; Ghasemi, Arash; Pourfallah, Tayyeb Allahverdi

    2015-01-01

    Purpose Mefenamic acid (MEF) as a non-steroidal anti-inflammatory drug is used as a medication for relieving of pain and inflammation. Radiation-induced inflammation process is involved in DNA damage and cell death. In this study, the radioprotective effect of MEF was investigated against genotoxicity induced by ionizing radiation in human blood lymphocytes. Materials and Methods Peripheral blood samples were collected from human volunteers and incubated with MEF at different concentrations (5, 10, 50, or 100 µM) for two hours. The whole blood was exposed to ionizing radiation at a dose 1.5 Gy. Lymphocytes were cultured with mitogenic stimulation to determine the micronuclei in cytokinesis blocked binucleated lymphocyte. Results A significant decreasing in the frequency of micronuclei was observed in human lymphocytes irradiated with MEF as compared to irradiated lymphocytes without MEF. The maximum decreasing in frequency of micronuclei was observed at 100 µM of MEF (38% decrease), providing maximal protection against ionizing radiation. Conclusion The radioprotective effect of MEF is probably related to anti-inflammatory property of MEF on human lymphocytes. PMID:26484310

  4. Oxygenated water does not induce genotoxic effects in the comet assay.

    PubMed

    Speit, Günter; Schütz, Petra; Trenz, Kristina; Rothfuss, Andreas

    2002-07-21

    Drinking of oxygenated water (i.e. water with increased concentration of physically dissolved oxygen) is said to improve oxygen availability of the body and will do the consumer good. However, increased oxygen concentrations can also lead to an increased production of reactive oxygen species (ROS). If antioxidant defences are not completely efficient, ROS can cause cell injury including DNA damage. We therefore investigated whether drinking of oxygenated water can lead to increased DNA damage in peripheral blood cells of test subjects. We also tested whether direct exposure of V79 Chinese hamster cells to oxygenated medium or oxygenated Hank's solution for various time periods induces DNA damage. Induction of DNA damage was measured with the alkaline comet assay (single cell gel electrophoresis). The comet assay, in particular the modification with FPG post-treatment for the determination of oxidative DNA base damage, has been proven to be extremely sensitive for the detection of oxygen-induced DNA damage. However, both the in vivo and the in vitro studies with the comet assay in the absence and presence of FPG post-treatment did not provide evidence for a genotoxic effect of oxygenated water.

  5. Investigation of the cytotoxic, genotoxic, and apoptosis-inducing effects of estragole isolated from fennel (Foeniculum vulgare).

    PubMed

    Villarini, Milena; Pagiotti, Rita; Dominici, Luca; Fatigoni, Cristina; Vannini, Samuele; Levorato, Sara; Moretti, Massimo

    2014-04-25

    The present study was undertaken to evaluate, in the HepG2 human hepatoma cell line, the in vitro cytotoxic, genotoxic, and apoptotic activities of estragole (1), contained in the essential oil of Foeniculum vulgare (fennel) and suspected to induce hepatic tumors in susceptible strains of mice. Toward this end, an MTT cytotoxicity assay, a trypan blue dye exclusion test, a double-staining (acridine orange and DAPI) fluorescence viability assay, a single-cell microgel-electrophoresis (comet) assay, a mitochondrial membrane potential (Δψm) assay, and a DNA fragmentation analysis were conducted. In terms of potential genotoxic effects, the comet assay indicated that estragole (1) was not able to induce DNA damage nor apoptosis under the experimental conditions used.

  6. Genotoxic Effects Induced by Cd(+2), Cr(+6), Cu(+2) in the Gill and Liver of Odontesthes bonariensis (Piscies, Atherinopsidae).

    PubMed

    Gasulla, J; Picco, S J; Carriquiriborde, P; Dulout, F N; Ronco, A E; de Luca, J C

    2016-05-01

    Genotoxic effects of Cd(+2), Cr(+6), and Cu(+2) on the gill and liver of the Argentinean Silverside (Odontesthes bonariensis) were studied using the comet assay and in relation with the metal tissue accumulation. Fish were exposed to three waterborne concentrations of each metal for 2 and 16 days. Genotoxicity was assessed by the single cell gel electrophoresis (comet assay). After 2 days, significant increase of the genetic damage index (GDI) was only observed in the gill of fish exposed to Cr(+6) and Cu(+2), and the LOECs were 2160 nM and 921.1 nM, respectively. The gill LOEC for Cd(+2) by 16 days was 9.4 nM. In the liver, LOECs were obtained only for Cd(+2) and Cr(+6) and were 9.4 and 2160 nM, respectively. The three metals were able to induce genotoxic effects at environmentally relevant concentrations and the gill was the most sensitive organ.

  7. Genotoxic Effects Induced by Cd(+2), Cr(+6), Cu(+2) in the Gill and Liver of Odontesthes bonariensis (Piscies, Atherinopsidae).

    PubMed

    Gasulla, J; Picco, S J; Carriquiriborde, P; Dulout, F N; Ronco, A E; de Luca, J C

    2016-05-01

    Genotoxic effects of Cd(+2), Cr(+6), and Cu(+2) on the gill and liver of the Argentinean Silverside (Odontesthes bonariensis) were studied using the comet assay and in relation with the metal tissue accumulation. Fish were exposed to three waterborne concentrations of each metal for 2 and 16 days. Genotoxicity was assessed by the single cell gel electrophoresis (comet assay). After 2 days, significant increase of the genetic damage index (GDI) was only observed in the gill of fish exposed to Cr(+6) and Cu(+2), and the LOECs were 2160 nM and 921.1 nM, respectively. The gill LOEC for Cd(+2) by 16 days was 9.4 nM. In the liver, LOECs were obtained only for Cd(+2) and Cr(+6) and were 9.4 and 2160 nM, respectively. The three metals were able to induce genotoxic effects at environmentally relevant concentrations and the gill was the most sensitive organ. PMID:27003804

  8. Protective effects of coffee diterpenes against aflatoxin B1-induced genotoxicity: mechanisms in rat and human cells.

    PubMed

    Cavin, C; Mace, K; Offord, E A; Schilter, B

    2001-06-01

    The coffee-specific diterpenes cafestol and kahweol (C + K) have been reported to be anticarcinogenic in several animal models. Proposed mechanisms involve a co-ordinated modulation of several enzymes responsible for carcinogen detoxification, thus preventing reactive agents interacting with critical target sites. To address the human relevance of the chemoprotective effects of C + K against aflatoxin B(1) (AFB1) genotoxicity observed in rat liver, and to compare the mechanisms of protection involved in both species, animal and human hepatic in vitro test systems were applied. In rat primary hepatocytes, C + K reduced the expression of cytochrome P450 CYP 2C11 and CYP 3A2, the key enzymes responsible for AFB1 activation to the genotoxic metabolite aflatoxin B1-8,9 epoxide (AFBO). In addition, these diterpenes induced significantly GST Yc2, the most efficient rat GST subunit involved in AFBO detoxification. These effects of C + K resulted in a marked dose-dependent inhibition of AFB1-DNA binding in this rat in vitro culture system. Their relevance in humans was addressed using liver epithelial cell lines (THLE) stably transfected to express AFB1 metabolising cytochrome P450s. In these cells, C + K also produced a significant inhibition of AFB1-DNA adducts formation linked with an induction of the human glutathione S-transferase GST-mu. Altogether, these results suggest that C + K may have chemoprotective activity against AFB1 genotoxicity in both rats and humans. PMID:11346484

  9. Effect of recombinant human erythropoietin on mitomycin C-induced oxidative stress and genotoxicity in rat kidney and heart tissues.

    PubMed

    Rjiba-Touati, K; Ayed-Boussema, I; Guedri, Y; Achour, A; Bacha, H; Abid-Essefi, S

    2016-01-01

    Mitomycin C (MMC) is an antineoplastic agent used for the treatment of several human malignancies. Nevertheless, the prolonged use of the drug may result in a serious heart and kidney injuries. Recombinant human erythropoietin (rhEPO) has recently been shown to exert an important cytoprotective effect in experimental brain injury and ischemic acute renal failure. The aim of the present work is to investigate the cardioprotective and renoprotective effects of rhEPO against MMC-induced oxidative damage and genotoxicity. Our results showed that MMC induced oxidative stress and DNA damage. rhEPO administration in any treatment conditions decreased oxidative damage induced by MMC. It reduced malondialdehyde and protein carbonyl levels. rhEPO ameliorated reduced glutathione plus oxidized glutathione modulation and the increased catalase activity after MMC treatment. Furthermore, rhEPO restored DNA damage caused by MMC. We concluded that rhEPO administration especially in pretreatment condition protected rats against MMC-induced heart and renal oxidative stress and genotoxicity.

  10. Chromium induced biochemical, genotoxic and histopathologic effects in liver and kidney of Goldfish, Carassius auratus

    PubMed Central

    Velma, Venkatramreddy; Tchounwou, Paul B.

    2010-01-01

    Fish constitute an excellent model to understand the mechanistic aspects of metal toxicity vis-à-vis oxidative stress in aquatic ecosystems. Hexavalent chromium (Cr (VI)), due to its redox potential can induce oxidative stress (OS) in fish and impair their health. In the present investigation, we hypothesize that OS plays a key role in chromium induced toxicity in goldfish; leading to the production of reactive oxygen species (ROS) such as O· 2, H2O2, OH·, and subsequent modulation of the activities of antioxidant enzymes such as catalase (CAT), superoxide dismutase (SOD), metallothioneins (MT), glutathione proxidase (GPx), genotoxicity and histopathology. To test this hypothesis, antioxidant enzymes, DNA damage and histopathology assays were performed in liver and kidney tissues of goldfish exposed to different concentrations of Cr (VI) (LC12.5, LC25 and LC50) following 96h static renewal bioassay. The results of this study clearly show that the fish experienced OS as characterized by significant modulation of enzyme activities, induction of DNA damage and microscopic morphological changes in the liver and kidney. In both tissues, CAT activity was decreased whereas SOD activity and hydroperoxide levels were increased. In addition, GPx activity also increased significantly in higher test concentrations, especially in the kidney. MT induction and DNA damage were observed in both tissues in a concentration dependent manner. Microscopic examination of organ morphology indicated degeneration of liver tissue and necrosis of central vein. Necrosis of kidney tubular epithelial cells and tubules was observed at higher Cr (VI) concentrations. Taking together the findings of this study are helpful in organ-specific risk assessment of Cr (VI)-induced oxidative stress, genotoxicity and histopathology in fish. PMID:20348018

  11. Genotoxic effects induced in cultured Chinese hamster ovary (CHO) cells by contaminated aquatic environments.

    PubMed

    Venegas, W; Garcia, M D

    1994-01-01

    The Bio-Bio river, running through one of the most important hydrographic basins in Chile, presents concentrations of some chemical agents exceeding the accepted values for continental aquatic environments. The area near to the mouth of the river is highly industrialized and the industrial effluents are discharge directly into the river, most of them without any previous treatment. This river provides the principal source of drinking water for a population of more than one million inhabitants in the region. To evaluate the genotoxic effects of liquid effluents from a cellulose industry and the surface waters of the Bio-Bio river obtained near to the river mouth in the proximity of Concepción city, a short-term bio-assay with cultured Chinese hamster ovary (CHO) cells was used. The frequency of cells with chromosome aberrations in metaphase, anaphase and telophase was determined at different concentrations of the liquid samples. The results show a significant increase in chromosomal damage. The frequency of chromosomal aberrations observed both in metaphase and ana-telophase is dose-related to the concentrations of liquid samples tested. The superficial water shows a significant genotoxic effect. The scope of these results is discussed and compared to results obtained in other biological models. PMID:8728834

  12. Disperse Red 1 (textile dye) induces cytotoxic and genotoxic effects in mouse germ cells.

    PubMed

    Fernandes, Fábio Henrique; Bustos-Obregon, Eduardo; Salvadori, Daisy Maria Fávero

    2015-06-01

    Disperse Red 1 (DR1), which is widely used in the textile industry, is an azo dye that contributes to the toxicity and pollution of wastewater. To assess the toxic effects of DR1 on reproduction, sexually mature male mice (Mus musculus, strain CF-1) were orally (gavage) treated with single doses of the compound at 20, 100 and 500 mg/kg body weight. Testicular features and sperm parameters were evaluated 8.3, 16.6 and 24.9 days after treatments. In addition to testicular toxicity caused by the dye, the data clearly showed an increased frequency of sperm with abnormal morphology and decreased fertility. An increased amount of DNA damage was also detected in testis cells 16.6 and 24.9 days after treatments with 100 and 500 mg/kg. This study demonstrated the toxic and genotoxic effects of DR1, indicating the harmful activity of this dye on reproductive health.

  13. Safrole-2',3'-oxide induces cytotoxic and genotoxic effects in HepG2 cells and in mice.

    PubMed

    Chiang, Su-yin; Lee, Pei-yi; Lai, Ming-tsung; Shen, Li-ching; Chung, Wen-sheng; Huang, Hui-fen; Wu, Kuen-yuh; Wu, Hsiu-ching

    2011-12-24

    Safrole-2',3'-oxide (SAFO) is a reactive electrophilic metabolite of the hepatocarcinogen safrole, the main component of sassafras oil. Safrole occurs naturally in a variety of spices and herbs, including the commonly used Chinese medicine Xi xin (Asari Radix et Rhizoma) and Dong quai (Angelica sinensis). SAFO is the most mutagenic metabolite of safrole tested in the Ames test. However, little or no data are available on the genotoxicity of SAFO in mammalian systems. In this study, we investigated the cytotoxicity and genotoxicity of SAFO in human HepG2 cells and male FVB mice. Using MTT assay, SAFO exhibited a dose- and time-dependent cytotoxic effect in HepG2 cells with TC(50) values of 361.9μM and 193.2μM after 24 and 48h exposure, respectively. In addition, treatment with SAFO at doses of 125μM and higher for 24h in HepG2 cells resulted in a 5.1-79.6-fold increase in mean Comet tail moment by the alkaline Comet assay and a 2.6-7.8-fold increase in the frequency of micronucleated binucleated cells by the cytokinesis-block micronucleus assay. Furthermore, repeated intraperitoneal administration of SAFO (15, 30, 45, and 60mg/kg) to mice every other day for a total of twelve doses caused a significant dose-dependent increase in mean Comet tail moment in peripheral blood leukocytes (13.3-43.4-fold) and in the frequency of micronucleated reticulocytes (1.5-5.8-fold). Repeated administration of SAFO (60mg/kg) to mice caused liver lesions manifested as a rim of ballooning degeneration of hepatocytes immediately surrounding the central vein. Our data clearly demonstrate that SAFO significantly induced cytotoxicity, DNA strand breaks, micronuclei formation both in human cells in vitro and in mice. More studies are needed to explore the role SAFO plays in safrole-induced genotoxicity.

  14. Carbamates: A study on genotoxic, cytotoxic, and apoptotic effects induced in Chinese hamster ovary (CHO-K1) cells.

    PubMed

    Soloneski, Sonia; Kujawski, Maciej; Scuto, Anna; Larramendy, Marcelo L

    2015-08-01

    In vitro effects of the carbamates pirimicarb and zineb and their formulations Aficida® (50% pirimicarb) and Azzurro® (70% zineb), respectively, were evaluated in Chinese hamster ovary (CHO-K1) cells. Whereas the cytokinesis-blocked micronucleus cytome assay was employed to test for genotoxicity, MTT, neutral red (NR), and apoptosis evaluation were used as tests for estimating cell viability and succinic dehydrogenase activity, respectively. Concentrations tested were 10-300 μg/ml for pirimicarb and Aficida®, and 1-50 μg/ml for zineb and Azzurro®. All compounds were able to increase the frequency of micronuclei. A marked reduction in the nuclear division index was observed after treatment with 5 μg/ml of zineb and Azzurro® and 10 μg/ml of Azzurro®. Alterations in the cellular morphology not allowing the recognition of binucleated cells exposed to 300 μg/ml pirimicarb and Aficida® as well as 10-50 μg/ml zineb and Azzurro®. All four compounds induced inhibition of both cell viability and succinic dehydrogenase activity and trigger apoptosis in CHO-K1 cells, at least when exposed for 24 h. The data herein demonstrate the genotoxic and cytotoxic effects exerted by these carbamates and reveal the potential risk factor of these pesticides, still extensively used worldwide, for both human health and the environment.

  15. Genotoxic effects induced by the exposure to an environmental mixture of illicit drugs to the zebra mussel.

    PubMed

    Parolini, Marco; Magni, Stefano; Castiglioni, Sara; Binelli, Andrea

    2016-10-01

    Despite the growing interest on the presence of illicit drugs in freshwater ecosystems, just recently the attention has been focused on their potential toxicity towards non-target aquatic species. However, these studies largely neglected the effects induced by exposure to complex mixtures of illicit drugs, which could be different compared to those caused by single psychoactive molecules. This study was aimed at investigating the genetic damage induced by a 14-day exposure to a realistic mixture of the most common illicit drugs found in surface waters worldwide (cocaine, benzoylecgonine, amphetamine, morphine and 3,4-methylenedioxymethamphetamine) on the zebra mussel (Dreissena polymorpha). The mixture caused a significant increase of DNA fragmentation and triggered the apoptotic process and micronuclei formation in zebra mussel hemocytes, pointing out its potential genotoxicity towards this bivalve species. PMID:27261879

  16. Protective effects of baicalein and wogonin against benzo[a]pyrene- and aflatoxin B(1)-induced genotoxicities.

    PubMed

    Ueng, Y F; Shyu, C C; Liu, T Y; Oda, Y; Lin, Y L; Liao, J F; Chen, C F

    2001-12-15

    To evaluate the protective effects of baicalein and wogonin against benzo[a]pyrene- and aflatoxin (AF) B(1)-induced toxicities, the effects of these flavonoids on the genotoxicities and oxidation of benzo[a]pyrene and AFB(1) were studied in C57BL/6J mice. Baicalein and wogonin reduced benzo[a]pyrene and AFB(1) genotoxicities as monitored by the umuC gene expression response in Salmonella typhimurium TA1535/pSK1002. Baicalein added in vitro decreased liver microsomal benzo[a]pyrene hydroxylation (AHH) activity with an ic(50) of 33.9 +/- 1.4 microM at 100 microM benzo[a]pyrene. Baicalein also inhibited AFQ(1) and AFB(1)-epoxide formation from AFB(1) (50 microM) oxidation (AFO) with ic(50) values of 22.8 +/- 1.4 and 5.3 +/- 0.8 microM, respectively. However, the in vitro inhibitory effects of wogonin on AHH and AFO activities in liver microsomes were less than those of baicalein as inhibition by 500 microM wogonin was only about 51-65%. Treatment of mice with liquid diets containing 5 mM baicalein and wogonin resulted in 22 and 49% decreases in hepatic AHH activities, respectively. Baicalein treatment resulted in 39 and 32% decreases in AFQ(1) and AFB(1)-epoxide formation from liver microsomal AFO, respectively. Wogonin treatment resulted in 39 and 47% decreases in AFQ(1) and AFB(1)-epoxide formation, respectively. A 1-week pretreatment with wogonin significantly decreased hepatic DNA adduct formation in mice treated with 200 mg/kg of benzo[a]pyrene via gastrogavage. These in vitro and in vivo effects suggested that baicalein and wogonin might have beneficial effects against benzo[a]pyrene- and AFB(1)-induced hepatic toxicities and that wogonin had a stronger protective effect in vivo. PMID:11755119

  17. Genotoxicity and genotoxic enhancing effect of tetrandrine in Salmonella typhimurium.

    PubMed

    Whong, W Z; Lu, C H; Stewart, J D; Jiang, H X; Ong, T

    1989-03-01

    Tetrandrine has been used for the treatment of silicosis in China. The potential genotoxic and carcinogenic hazards of this drug were studied using the Salmonella/histidine reversion assay and the SOS/Umu test. The results show that tetrandrine was weakly mutagenic to Salmonella typhimurium TA98 with metabolic activation and did not induce SOS response. However, tetrandrine increased the mutagenic activity of benzo[alpha]pyrene, trinitrofluorenone (TNF), 2-aminoanthracene (2AA), diesel emission particles, airborne particles, and cigarette smoke condensate by more than 100%; the activity of aflatoxin B1 and fried beef was increased by over 75%. It also increased the 2AA and TNF-induced SOS response by more than 300%. These results indicated that tetrandrine was a weak promutagen inducing frameshift mutations and was a potent genotoxic enhancer. The mechanism for the genotoxic enhancement is not known. However, the fact that the increase in mutagenicity was noted only in TA98 and not in TA1538 suggested that the enhancement of genotoxicity by tetrandrine may result from an increase in error-prone DNA repair. PMID:2646534

  18. Effect of probiotic fermented milk and chlorophyllin on gene expressions and genotoxicity during AFB₁-induced hepatocellular carcinoma.

    PubMed

    Kumar, Manoj; Verma, Vinod; Nagpal, Ravinder; Kumar, Ashok; Gautam, Sanjeev K; Behare, Pradip V; Grover, Chand R; Aggarwal, Praveen K

    2011-12-15

    The aim of this study was to investigate the chemopreventive effect of probiotic fermented milk and chlorophyllin on aflatoxin B₁ (AFB₁) induced hepatocellular carcinoma. In vivo trials were conducted on 200 Wistar rats allocated to eight groups. Rats in the positive control group were given intraperitoneal injection of aflatoxin B₁ at 450 μg/kg body weight twice a week for 6 weeks. The rats were sacrificed and dissected at 25th week of the experiment, and comet assay was carried out in hepatic cells to assess the genotoxicity or DNA damage. The tumour incidence was decreased by approximately one-third than AFB₁ control group. The expression of c-myc bax, bcl-2, cyclin D1, p53 and rasp-21 genes was also studied. A significant (P<0.05) reduction in DNA damage was observed in probiotic fermented milk with chlorophyllin group as compared to aflatoxin B₁ control group. The c-myc, bcl-2, cyclin D1 and rasp-21 level was found to be highest in AFB₁ control group as compared to the treatment group. The results advocate the enhanced protective potential of probiotic fermented milk and chlorophyllin against AFB₁-induced molecular alterations in hepatic cells during carcinogenesis. PMID:21963996

  19. Protecting effect of caffeine against vinblastine (an anticancer drug) induced genotoxicity in mice.

    PubMed

    Geriyol, Prakash; Basavanneppa, Hosetti Basaling; Dhananjaya, Bhadrapura Lakkappa

    2015-04-01

    Vinblastine a DNA non-intercalating agent has wide application against several human neoplasms, and found to cause cytogenotoxicity. In this study, clastogenotoxicity of vinblastine (1.5 mg/kg b w) and its prevention by caffeine at different doses (25, 50 and 100 mg/kg b w) administered intraperitoneally was assessed in in vivo mice. It was found that micronucleus level had decreased significantly (up to 28.8%) in 100 mg caffeine treated group at 30 h post treatment. However, it did not exhibit protective effect against chromosomal aberration in spaermatogonial cells at 24 h post treatment. The frequencies of aberrant primary spermatocytes had decreased significantly in 25 and 100 mg caffeine at 4th week of post treatment. Similarly, in 100 mg of caffeine administered, abnormal sperm level had reduced (4.01%) significantly at 8th week post treatment. Thus, caffeine decreased the vinblastine induced chromosomal aberrations and mitotic index in bone marrow cells. In conclusion, this study shows that caffeine exerts protective effect against vinblastin induced cytogenotoxicity. Further studies on molecular mechanism are interesting in order to develop it as an effective drug in cancer chemotherapy.

  20. Genotoxic effects of arsenic: prevention by functional food-jaggery.

    PubMed

    Singh, Nrashant; Kumar, D; Raisuddin, S; Sahu, Anand P

    2008-09-18

    Arsenic contamination in groundwater is global human health hazard. There is no effective remedial action of chronic arsenicosis, however, a well-nourished diet can modulate the onset of adverse health effects and the delayed effect of arsenic in drinking water. In the present work, genotoxic effects induced by arsenic through parenteral administration and ameliorate by jaggery. Chromosomal aberrations were more pronounced in arsenic treated mice, while supplementation of jaggery with arsenic reduced the incidence of the aberrations. The outcome of study showed that Jaggery the natural functional food has the efficiency to encounter the genotoxic effects induced by arsenic.

  1. Differential effect of manool--a diterpene from Salvia officinalis, on genotoxicity induced by methyl methanesulfonate in V79 and HepG2 cells.

    PubMed

    Nicolella, Heloiza Diniz; de Oliveira, Pollyanna Francielli; Munari, Carla Carolina; Costa, Gizela Faleiros Dias; Moreira, Monique Rodrigues; Veneziani, Rodrigo Cassio Sola; Tavares, Denise Crispim

    2014-10-01

    Salvia officinalis (sage) is a perennial woody subshrub native to the Mediterranean region that is commonly used as a condiment and as an anti-inflammatory, antioxidant and antimicrobial agent due to its biological activities. Manool is the most abundant micro-metabolite found in Salvia officinalis essential oils and extracts. We therefore decided to evaluate the cytotoxic, genotoxic and antigenotoxic potential of manool in Chinese hamster lung fibroblasts (V79) and human hepatoma cells (HepG2). Cytotoxicity was assessed by the colony-forming assay in V79 cells and toxic effects were observed at concentrations of up to 8.0 μg/mL. The micronucleus test was used to evaluate the genotoxicity and antigenotoxicity of manool in V79 and HepG2 cells at concentrations of 0.5-6.0 μg/mL and 0.5-8.0 μg/mL, respectively. For evaluation of antigenotoxicity, the concentrations of manool were combined with methyl methanesulfonate (MMS, 44 μg/mL). The results showed a significant increase in the frequency of micronuclei in cultures of both cell lines treated with the highest concentration tested, demonstrating a genotoxic effect. On the other hand, manool exhibited a protective effect against chromosome damage induced by MMS in HepG2 cells, but not in V79 cells. These data suggest that some manool metabolite may be responsible for the antigenotoxic effect observed in HepG2 cells.

  2. Comparison of the genotoxic effects induced by 50 Hz extremely low-frequency electromagnetic fields and 1800 MHz radiofrequency electromagnetic fields in GC-2 cells.

    PubMed

    Duan, Weixia; Liu, Chuan; Zhang, Lei; He, Mindi; Xu, Shangcheng; Chen, Chunhai; Pi, Huifeng; Gao, Peng; Zhang, Yanwen; Zhong, Min; Yu, Zhengping; Zhou, Zhou

    2015-03-01

    Extremely low-frequency electromagnetic fields (ELF-EMF) and radiofrequency electromagnetic fields (RF-EMF) have been considered to be possibly carcinogenic to humans. However, their genotoxic effects remain controversial. To make experiments controllable and results comparable, we standardized exposure conditions and explored the potential genotoxicity of 50 Hz ELF-EMF and 1800 MHz RF-EMF. A mouse spermatocyte-derived GC-2 cell line was intermittently (5 min on and 10 min off) exposed to 50 Hz ELF-EMF at an intensity of 1, 2 or 3 mT or to RF-EMF in GSM-Talk mode at the specific absorption rates (SAR) of 1, 2 or 4 W/kg. After exposure for 24 h, we found that neither ELF-EMF nor RF-EMF affected cell viability using Cell Counting Kit-8. Through the use of an alkaline comet assay and immunofluorescence against γ-H2AX foci, we found that ELF-EMF exposure resulted in a significant increase of DNA strand breaks at 3 mT, whereas RF-EMF exposure had insufficient energy to induce such effects. Using a formamidopyrimidine DNA glycosylase (FPG)-modified alkaline comet assay, we observed that RF-EMF exposure significantly induced oxidative DNA base damage at a SAR value of 4 W/kg, whereas ELF-EMF exposure did not. Our results suggest that both ELF-EMF and RF-EMF under the same experimental conditions may produce genotoxicity at relative high intensities, but they create different patterns of DNA damage. Therefore, the potential mechanisms underlying the genotoxicity of different frequency electromagnetic fields may be different.

  3. Effect of cotreatment of aspirin metabolites on mitomycin C-induced genotoxicity using the somatic mutation and recombination test in Drosophila melanogaster.

    PubMed

    Niikawa, Miki; Nakamura, Takeshi; Nagase, Hisamitsu

    2006-01-01

    In our previous reports, aspirin, an antipyretic analgesic, suppressed the genotoxicity of mitomycin C (MMC) in a somatic mutation and recombination test (SMART) in Drosophila melanogaster. In order to reveal the mechanism of the anti-genotoxicity of aspirin, we evaluated the suppressing ability of each aspirin metabolite, such as salicylic acid (SA), salicyluric acid (SUA), gentisic acid (GA), gentisuric acid (GUA), and 2,3-dihydroxybenzoic acid (DHBA), in SMART in Drosophila melanogaster using the cotreatment protocol in this report. SUA, GA, GUA, and DHBA reduced the number of the three types of spot induced by MMC without decrease of survival. These aspirin metabolites decreased the genotoxicity frequency of MMC for total spots in a dose-dependent manner. Furthermore, each metabolite decreased the genotoxicity frequency of MMC by approximately 80% at a dose of 40 mg/bottle, respectively. It is suggested that these metabolites are the main substances of anti-genotoxicity in the aspirin metabolic pathway. PMID:16931440

  4. Protective effects of niacin against methylmercury-induced genotoxicity and alterations in antioxidant status in rats.

    PubMed

    Silva de Paula, Eloisa; Carneiro, Maria Fernanda Hornos; Grotto, Denise; Hernandes, Lívia Cristina; Antunes, Lusânia Maria Greggi; Barbosa, Fernando

    2016-01-01

    This study investigates the potential beneficial effects of niacin (NA; vitamin B3) supplementation in rats chronically exposed to methylmercury (MeHg). Animals were randomly assigned to one of 4 groups (n = 6): Group I, control, received distilled water by gavage; Group II, received MeHg (100 µg/kg/d) by gavage; Group III, received NA (50 mg/kg/d) in drinking water; Group IV, received MeHg (100 µg/kg/d) by gavage + NA (50 mg/kg/d) in drinking water. Biochemical parameters levels of glucose, triglycerides, total cholesterol and fractions, and enzyme activities aspartate transaminase (AST) and alanine transaminase (ALT) were determined. Further, oxidative stress markers activity of glutathione peroxidase (GPx) and catalase (CAT) activity, as well as levels of reduced glutathione (GSH), malondialdehyde (MDA), and nitric oxide, were examined, and the comet assay was performed, using blood/plasma. Hg levels were measured in blood, brain, and kidneys of animals. Our results demonstrated that NA reduced adverse effects produced by MeHg. The mechanism underlying these effects appears to be related to the intrinsic antioxidant potential of NA. Considering the beneficial effects attributed to NA following MeHg exposure and that fish are the main source of both NA and MeHg, future studies need to evaluate the potential counteractive effect of NA against the adverse consequences of MeHg exposure in fish-eating populations. PMID:26914397

  5. Protective effects of niacin against methylmercury-induced genotoxicity and alterations in antioxidant status in rats.

    PubMed

    Silva de Paula, Eloisa; Carneiro, Maria Fernanda Hornos; Grotto, Denise; Hernandes, Lívia Cristina; Antunes, Lusânia Maria Greggi; Barbosa, Fernando

    2016-01-01

    This study investigates the potential beneficial effects of niacin (NA; vitamin B3) supplementation in rats chronically exposed to methylmercury (MeHg). Animals were randomly assigned to one of 4 groups (n = 6): Group I, control, received distilled water by gavage; Group II, received MeHg (100 µg/kg/d) by gavage; Group III, received NA (50 mg/kg/d) in drinking water; Group IV, received MeHg (100 µg/kg/d) by gavage + NA (50 mg/kg/d) in drinking water. Biochemical parameters levels of glucose, triglycerides, total cholesterol and fractions, and enzyme activities aspartate transaminase (AST) and alanine transaminase (ALT) were determined. Further, oxidative stress markers activity of glutathione peroxidase (GPx) and catalase (CAT) activity, as well as levels of reduced glutathione (GSH), malondialdehyde (MDA), and nitric oxide, were examined, and the comet assay was performed, using blood/plasma. Hg levels were measured in blood, brain, and kidneys of animals. Our results demonstrated that NA reduced adverse effects produced by MeHg. The mechanism underlying these effects appears to be related to the intrinsic antioxidant potential of NA. Considering the beneficial effects attributed to NA following MeHg exposure and that fish are the main source of both NA and MeHg, future studies need to evaluate the potential counteractive effect of NA against the adverse consequences of MeHg exposure in fish-eating populations.

  6. DNA damage and oxidative stress induced by CeO2 nanoparticles in human dermal fibroblasts: Evidence of a clastogenic effect as a mechanism of genotoxicity.

    PubMed

    Benameur, Laila; Auffan, Mélanie; Cassien, Mathieu; Liu, Wei; Culcasi, Marcel; Rahmouni, Hidayat; Stocker, Pierre; Tassistro, Virginie; Bottero, Jean-Yves; Rose, Jérôme; Botta, Alain; Pietri, Sylvia

    2015-01-01

    The broad range of applications of cerium oxide (CeO2) nanoparticles (nano-CeO2) has attracted industrial interest, resulting in greater exposures to humans and environmental systems in the coming years. Their health effects and potential biological impacts need to be determined for risk assessment. The aims of this study were to gain insights into the molecular mechanisms underlying the genotoxic effects of nano-CeO2 in relation with their physicochemical properties. Primary human dermal fibroblasts were exposed to environmentally relevant doses of nano-CeO2 (mean diameter, 7 nm; dose range, 6 × 10(-5)-6 × 10(-3) g/l corresponding to a concentration range of 0.22-22 µM) and DNA damages at the chromosome level were evaluated by genetic toxicology tests and compared to that induced in cells exposed to micro-CeO2 particles (mean diameter, 320 nm) under the same conditions. For this purpose, cytokinesis-blocked micronucleus assay in association with immunofluorescence staining of centromere protein A in micronuclei were used to distinguish between induction of structural or numerical chromosome changes (i.e. clastogenicity or aneuploidy). The results provide the first evidence of a genotoxic effect of nano-CeO2, (while not significant with micro-CeO2) by a clastogenic mechanism. The implication of oxidative mechanisms in this genotoxic effect was investigated by (i) assessing the impact of catalase, a hydrogen peroxide inhibitor, and (ii) by measuring lipid peroxidation and glutathione status and their reversal by application of N-acetylcysteine, a precusor of glutathione synthesis in cells. The data are consistent with the implication of free radical-related mechanisms in the nano-CeO2-induced clastogenic effect, that can be modulated by inhibition of cellular hydrogen peroxide release. PMID:25325158

  7. DNA damage and oxidative stress induced by CeO2 nanoparticles in human dermal fibroblasts: Evidence of a clastogenic effect as a mechanism of genotoxicity.

    PubMed

    Benameur, Laila; Auffan, Mélanie; Cassien, Mathieu; Liu, Wei; Culcasi, Marcel; Rahmouni, Hidayat; Stocker, Pierre; Tassistro, Virginie; Bottero, Jean-Yves; Rose, Jérôme; Botta, Alain; Pietri, Sylvia

    2015-01-01

    The broad range of applications of cerium oxide (CeO2) nanoparticles (nano-CeO2) has attracted industrial interest, resulting in greater exposures to humans and environmental systems in the coming years. Their health effects and potential biological impacts need to be determined for risk assessment. The aims of this study were to gain insights into the molecular mechanisms underlying the genotoxic effects of nano-CeO2 in relation with their physicochemical properties. Primary human dermal fibroblasts were exposed to environmentally relevant doses of nano-CeO2 (mean diameter, 7 nm; dose range, 6 × 10(-5)-6 × 10(-3) g/l corresponding to a concentration range of 0.22-22 µM) and DNA damages at the chromosome level were evaluated by genetic toxicology tests and compared to that induced in cells exposed to micro-CeO2 particles (mean diameter, 320 nm) under the same conditions. For this purpose, cytokinesis-blocked micronucleus assay in association with immunofluorescence staining of centromere protein A in micronuclei were used to distinguish between induction of structural or numerical chromosome changes (i.e. clastogenicity or aneuploidy). The results provide the first evidence of a genotoxic effect of nano-CeO2, (while not significant with micro-CeO2) by a clastogenic mechanism. The implication of oxidative mechanisms in this genotoxic effect was investigated by (i) assessing the impact of catalase, a hydrogen peroxide inhibitor, and (ii) by measuring lipid peroxidation and glutathione status and their reversal by application of N-acetylcysteine, a precusor of glutathione synthesis in cells. The data are consistent with the implication of free radical-related mechanisms in the nano-CeO2-induced clastogenic effect, that can be modulated by inhibition of cellular hydrogen peroxide release.

  8. Lagos lagoon sediment organic extracts and polycyclic aromatic hydrocarbons induce embryotoxic, teratogenic and genotoxic effects in Danio rerio (zebrafish) embryos.

    PubMed

    Sogbanmu, Temitope O; Nagy, Eszter; Phillips, David H; Arlt, Volker M; Otitoloju, Adebayo A; Bury, Nic R

    2016-07-01

    An expansion of anthropogenic activity around Lagos lagoon, Nigeria, has raised concerns over increasing contaminants entering the lagoon's ecosystem. The embryotoxicity, teratogenicity and genotoxicity of sediment organic extracts from four sampling zones around Lagos lagoon, Ilaje, Iddo, Atlas Cove and Apapa, as well as the dominant polycyclic aromatic hydrocarbons (PAHs) identified in water measured during the wet season (naphthalene, phenanthrene, pyrene, benzo[a]pyrene and a mixture of these), were assessed with Danio rerio embryos. Embryos were exposed to varying concentrations of toxicants from 0-72 h post-fertilization (hpf). Embryotoxicity at 72 hpf showed a dose-dependent increase in mortality upon exposure to extracts from all zones, except Atlas Cove. Similarly, higher levels of teratogenic effects, such as increased oedema, and haemorrhage and developmental abnormalities resulted from exposure to extracts from Ilaje, Iddo and Apapa zones. Treatment with single PAHs revealed that significant levels of detrimental effects were obtained only for phenanthrene. The modified comet assay revealed that the oxidative damage to DNA was generally low (<12 %) overall for all sediment extracts, but was significantly elevated with Ilaje and Iddo sediment extracts when compared with solvent controls. Oxidative damage was observed with the single PAHs, phenanthrene and benzo[a]pyrene, as well as with the PAH mixture. This study highlights that Lagos lagoon sediment extracts have teratogenic, embryotoxic and genotoxic properties, which are likely due to the high molecular weight PAHs present in the extracts, some of which are known or are suspected human carcinogens. PMID:27068906

  9. Effectiveness of activated carbon and Egyptian montmorillonite in the protection against deoxynivalenol-induced cytotoxicity and genotoxicity in rats.

    PubMed

    Abdel-Wahhab, Mosaad A; El-Kady, Ahmed A; Hassan, Aziza M; Abd El-Moneim, Omaima M; Abdel-Aziem, Sekena H

    2015-09-01

    This study was conducted to prepare and characterize activated carbon (AC) and to evaluate its protective effect against deoxynivalenol (DON) toxicity in rats compared to Egyptian montmorillonite (EM). AC was prepared using a single-step chemical activation with phosphoric acid (H3PO4). The resulted AC has a high surface area and a high total pore volume. Male Sprague-Dawley rats were divided into 6 groups (n = 10) and treated for 3 weeks as follow: the control group, the groups fed AC or EM-supplemented diet (0.5% w/w), the group treated orally with DON (5 mg/kg b.w.) and the groups fed AC or EM-supplemented diet and treated with DON. Blood and liver samples were collected for different analyses. Treatment with DON increased liver function enzymes, lipid peroxidation, tumor necrosis factor α, DNA fragmentation, decreased hepatic glutathione content, up regulating mRNA Fas and TNF-α genes expression and increased micronucleated polychromatic erythrocytes and normochromatic erythrocytes in bone marrow. Co-treatment of DON plus AC or EM succeeded to normalize the levels of the biochemical parameters, reduced the cytotoxicity of bone marrow and ameliorated the hepatic genotoxicity. Moreover, AC was more effective than EM and has a high affinity to adsorb DON and to reduce its cytotoxicity and genotoxicity.

  10. Lack of an EMF-induced genotoxic effect in the Ames assay.

    PubMed

    Morandi, M A; Pak, C M; Caren, R P; Caren, L D

    1996-01-01

    A few epidemiological studies have linked exposure to electromagnetic fields (EMF) and the incidence of cancer. Since many carcinogens are mutagens in the Ames assay, the purpose of this study was to determine if exposure of four tester strains of Salmonella typhimurium (TA97a, TA98, TA100, and TA102) to EMF would increase their rate of mutation. Parallel plate electrodes and Helmholtz coils were used to create uniform field properties (300 V/in., 0.3 mT). Separate and combined alternating electric and magnetic fields effects were studied at a combined field frequency of 60, 600, and 6000 Hz at room temperature. These fields did not elevate the temperature of the culture plates above room temperature, Petri dishes containing each tester strain in top agar were exposed to an electric field (E), magnetic field (M), combined electric and magnetic field (EM), or no additional field above ambient conditions in the lab (control). Four plates containing each strain were exposed in each condition: two plates had the appropriate positive-control mutagen for each strain included in the top agar and two plates did not. Plates were exposed to either E, M, EM, or control conditions at room temperature for 48 hr. and then incubated an additional 24 hr. at 37 deg. C. The plates containing mutagen in the top agar showed an increased number of colonies consistent with mutagenesis. However, the rate of mutation in the S. typhimurium strains TA97a, TA98, TA100, and TA102 in either the presence or absence of mutagen was not affected by 48 hr. exposure at room temperature to E, M, or EM fields at 60, 600, or 6000 Hz. PMID:8699937

  11. Chemopreventive effects of Furan-2-yl-3-pyridin-2-yl-propenone against 7,12-dimethylbenz[a]anthracene-inducible genotoxicity

    SciTech Connect

    Hwang, Yong Pil; Han, Eun Hee; Choi, Jae Ho; Kim, Hyung Gyun; Lee, Kyung Jin; Jeong, Tae Cheon; Lee, Eung Seok; Jeong, Hye Gwang

    2008-05-01

    1-Furan-2-yl-3-pyridin-2-yl-propenone (FPP-3) is an anti-inflammatory agent with a propenone moiety and chemically synthesized recently. In this study, we examined the chemopreventive effect of FPP-3 on 7,12-dimethylbenz[a]anthracene (DMBA)-induced genotoxicity in MCF-7 cells. FPP-3 reduced the formation of the DMBA-DNA adduct. DMBA-induced CYP1A1 and CYP1B1 gene expression and enzyme activity were inhibited by FPP-3. It inhibited DMBA-induced aryl hydrocarbon receptor (AhR) transactivation and DMBA-inducible nuclear localization of the AhR. Induction of detoxifying phase II genes by chemopreventive agents represents a coordinated protective response against oxidative stress and neoplastic effects of carcinogens. Transcription factor NF-E2 related factor 2 (Nrf2) regulates antioxidant response element (ARE) of phase II detoxifying and antioxidant enzymes, such as glutathione S-transferase (GST) and NAD(P)H:quinone oxidoreductase (QR). FPP-3 increased the expression and enzymatic activity of GST and QR. Moreover, FPP-3 increased transcriptional activity of GST and QR. GST and QR induction and Nrf2 translocation by FPP-3 were blocked by the PKC inhibitor Goe6983, and the p38 inhibitor SB203580. These results reflected a partial role of PKC{delta} and p38 signaling in FPP-3-mediated GSTA and QR induction through nuclear translocation of Nrf2. Classically, chemopreventive agents either inhibit CYP metabolizing enzyme or induce phase II detoxifying enzymes. These results suggest that FPP-3 has a potent protective effect against DMBA-induced genotoxicity through modulating phase I and II enzymes and that it has potential as a chemopreventive agent.

  12. Uptake of inorganic and organic derivatives of arsenic associated with induced cytotoxic and genotoxic effects in Chinese hamster ovary (CHO) cells.

    PubMed

    Dopp, E; Hartmann, L M; Florea, A-M; von Recklinghausen, U; Pieper, R; Shokouhi, B; Rettenmeier, A W; Hirner, A V; Obe, G

    2004-12-01

    Humans are exposed to arsenic and their organic derivatives, which are widely distributed in the environment, via food, water, and to a lesser extent, via air. Following uptake, inorganic arsenic undergoes biotransformation to mono- and dimethylated metabolites. Recent findings suggest that the methylation reactions represent a toxification rather than a detoxification pathway. In the present study, the genotoxic effects and the cellular uptake of inorganic arsenic [arsenate, As(i)(V); arsenite, As(i)(III)] and the methylated arsenic species monomethylarsonic acid [MMA(V)], monomethylarsonous acid [MMA(III)], dimethylarsinic acid [DMA(V)], dimethylarsinous acid [DMA(III)], trimethylarsenic oxide [TMAO(V)] were investigated in Chinese hamster ovary (CHO-9) cells. The chemicals were applied at different concentrations (0.1 microM to 10 mM) for 30 min and 1 h, respectively. Cytotoxic effects were investigated by the trypan blue extrusion test and genotoxic effects by the assessment of micronucleus (MN) induction, chromosome aberrations (CA), and sister chromatid exchanges (SCE). Intracellular arsenic concentrations were determined by ICP-MS techniques. Our results show that MMA(III) and DMA(III) induce cytotoxic and genotoxic effects to a greater extent than MMA(V) or DMA(V). Viability was significantly decreased after incubation (1 h) of the cells with > or = 1 microM As(i)(III), > or = 1 microM As(i)(V), > or = 500 microM MMA(III), > or = 100 microM MMA(V), and 500 microM DMA(V) and > or = 0.1 microM DMA(III). TMAO(V) was not cytotoxic at concentrations up to 10 mM. A significant increase of the number of MN, CA and SCE was found for DMA(III) and MMA(III). As(i)(III + V) induced CA and SCE but no MN. TMAO(V), MMA(V) and DMA(V) were not genotoxic in the concentration range tested (up to 5 mM). The nuclear division index (NDI) was not affected by any of the tested arsenic compounds after a recovery period of 14 to 35 h. When the uptake of the chemicals was measured by

  13. Effect of PCB153 on BaP-induced genotoxicity in HepG2 cells via modulation of metabolic enzymes.

    PubMed

    Wei, Wei; Zhang, Chi; Liu, Ai-Lin; Xie, Shao-Hua; Chen, Xue-Min; Lu, Wen-Qing

    2009-04-30

    Benzo(a)pyrene (BaP) is a representative environmental carcinogen and is metabolically activated by several cytochrome P450 (CYP) enzymes to become the ultimate carcinogen. Numerous studies have indicated that 2,2',4,4',5,5'-hexachlorobiphenyl (PCB153) could effectively alter the activity of xenobiotic metabolizing enzymes (XMEs). Therefore, we propose that PCB153 may affect BaP-induced genotoxicity mediated by XMEs. In the present study, we treated HepG2 cells with BaP (50 microM) or PCB153 (0.1, 1, 10 and 100 microM), or pretreated the cells with PCB153 for 48 h followed by treatment with a combination of both BaP and PCB153. CYP1A1 activity was dramatically increased in cells treated with either BaP or PCB153. Glutathione-S-transferase (GST) activity was increased in BaP-treated cells, but decreased in PCB153-treated cells. In parallel to studies on enzyme activity, the micronuclei (MN) assay was used to assess the genotoxic damage caused by BaP and PCB153. BaP and PCB153 at 100 microM enhanced MN formation. In contrast to BaP treatment alone, treatment with both BaP and PCB153 significantly enhanced the activity of CYP1A1 and the formation of MN, but reduced the activity of GST. alpha-Naphthoflavone (ANF), an inhibitor of CYP1A1, inhibited MN formation in the presence of both BaP and PCB153. In addition, there was a positive correlation between CYP1A activity and MN formation (r(2)=0.794, P<0.001). Our observations suggest that co-exposure to BaP and PCB153 may increase BaP-induced genotoxicity, possibly through the induction of CYP1A1 and inhibition of GST.

  14. Ameliorative effects of thyme and calendula extracts alone or in combination against aflatoxins-induced oxidative stress and genotoxicity in rat liver.

    PubMed

    Abdel-Aziem, Sekena H; Hassan, Aziza M; El-Denshary, Ezzeldein S; Hamzawy, Mohamed A; Mannaa, Fathia A; Abdel-Wahhab, Mosaad A

    2014-05-01

    The aims of the current work were to evaluate the hepatoprotective effect of calendula flowers and/or thyme leave extracts on aflatoxins (AFs)-induced oxidative stress, genotoxicity and alteration of p53 bax and bcl2 gene expressions. Eighty male Sprague-Dawley rats were divided into eight equal groups including: the control group, the group fed AFs-contaminated diet (2.5 mg/kg diet) for 5 weeks, the groups treated orally with thyme and/or calendula extract (0.5 g/kg b.w) for 6 weeks and the groups pretreated orally with thyme and/or calendula extract 1 week before and during AFs treatment for further 5 weeks. Blood, liver and bone marrow samples were collected for biochemical analysis, gene expression, DNA fragmentation and micronucleus assay. The results showed that AFs induced significant alterations in oxidative stress markers, increased serum AFP and inflammatory cytokine, percentage of DNA fragmentation, the expression of pro-apoptotic gene p53 and bax accompanied with a decrease in the expression of bcl2. Animals treated with the extracts 1 week before AFs treatment showed a significant decrease in oxidative damage markers, micronucleated cells, DNA fragmentation and modulation of the expression of pro-apoptotic genes. These results suggested that both calendula and thyme extracts had anti-genotoxic effects due to their higher content of total phenolic compounds. PMID:24096837

  15. Ameliorative effects of thyme and calendula extracts alone or in combination against aflatoxins-induced oxidative stress and genotoxicity in rat liver.

    PubMed

    Abdel-Aziem, Sekena H; Hassan, Aziza M; El-Denshary, Ezzeldein S; Hamzawy, Mohamed A; Mannaa, Fathia A; Abdel-Wahhab, Mosaad A

    2014-05-01

    The aims of the current work were to evaluate the hepatoprotective effect of calendula flowers and/or thyme leave extracts on aflatoxins (AFs)-induced oxidative stress, genotoxicity and alteration of p53 bax and bcl2 gene expressions. Eighty male Sprague-Dawley rats were divided into eight equal groups including: the control group, the group fed AFs-contaminated diet (2.5 mg/kg diet) for 5 weeks, the groups treated orally with thyme and/or calendula extract (0.5 g/kg b.w) for 6 weeks and the groups pretreated orally with thyme and/or calendula extract 1 week before and during AFs treatment for further 5 weeks. Blood, liver and bone marrow samples were collected for biochemical analysis, gene expression, DNA fragmentation and micronucleus assay. The results showed that AFs induced significant alterations in oxidative stress markers, increased serum AFP and inflammatory cytokine, percentage of DNA fragmentation, the expression of pro-apoptotic gene p53 and bax accompanied with a decrease in the expression of bcl2. Animals treated with the extracts 1 week before AFs treatment showed a significant decrease in oxidative damage markers, micronucleated cells, DNA fragmentation and modulation of the expression of pro-apoptotic genes. These results suggested that both calendula and thyme extracts had anti-genotoxic effects due to their higher content of total phenolic compounds.

  16. Assessment of isorhamnetin 3-O-neohesperidoside from Acacia salicina: protective effects toward oxidation damage and genotoxicity induced by aflatoxin B1 and nifuroxazide.

    PubMed

    Bouhlel, Ines; Limem, Ilef; Skandrani, Ines; Nefatti, Aicha; Ghedira, Kamel; Dijoux-Franca, Marie-Genevieve; Leila, Chekir-Ghedira

    2010-08-01

    Antioxidant activity of isorhamnetin 3-O-neohesperidoside, isolated from the leaves of Acacia salicina, was determined by the ability of this compound to inhibit xanthine oxidase activity and to scavenge the free radical 2,2'-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) (ABTS(.-)) diammonium salt. Antigenotoxic activity was assessed using the SOS chromotest assay. This compound has the ability to scavenge the ABTS(.+) radical by a hydrogen donating mechanism. We also envisaged the study of the antioxidant effect of this compound by the enzymatic xanthine/xanthine oxidase (X/XOD) assay. Results indicated that isorhamnetin 3-O-neohesperidoside was a potent inhibitor of xanthine oxidase and superoxide anion scavengers. Moreover, this compound induced an inhibitory activity against nifuroxazide and aflatoxine B1 (AFB1) induced genotoxicity. Taken together, these observations provide evidence that isorhamnetin 3-O-neohesperidoside isolated from the leaves of A. salicina is able to protect cells against the consequences of oxidative stress. PMID:20809543

  17. Nongenotoxic effects and a reduction of the DXR-induced genotoxic effects of Helianthus annuus Linné (sunflower) seeds revealed by micronucleus assays in mouse bone marrow

    PubMed Central

    2014-01-01

    Background This research evaluated the genotoxicity of oil and tincture of H. annuus L. seeds using the micronucleus assay in bone marrow of mice. The interaction between these preparations and the genotoxic effects of doxorubicin (DXR) was also analysed (antigenotoxicity test). Methods Experimental groups were evaluated at 24-48 h post treatment with N-Nitroso-N-ethylurea (positive control – NEU), DXR (chemotherapeutic), NaCl (negative control), a sunflower tincture (THALS) and two sources of sunflower oils (POHALS and FOHALS). Antigenotoxic assays were carried out using the sunflower tincture and oils separately and in combination with NUE or DXR. Results For THALS, analysis of the MNPCEs showed no significant differences between treatment doses (250–2,000 mg.Kg-1) and NaCl. A significant reduction in MNPCE was observed when THALS (2,000 mg.Kg-1) was administered in combination with DXR (5 mg.Kg-1). For POHALS or FOHALS, analysis of the MNPCEs also showed no significant differences between treatment doses (250–2,000 mg.Kg-1) and NaCl. However, the combination DXR + POHALS (2,000 mg.Kg-1) or DXR + FOHALS (2,000 mg.Kg-1) not contributed to the MNPCEs reduction. Conclusions This research suggests absence of genotoxicity of THALS, dose-, time- and sex-independent, and its combination with DXR can reduce the genotoxic effects of DXR. POHALS and FOHALS also showed absence of genotoxicity, but their association with DXR showed no antigenotoxic effects. PMID:24694203

  18. Characteristic expression profiles induced by genotoxic carcinogens in rat liver.

    PubMed

    Ellinger-Ziegelbauer, Heidrun; Stuart, Barry; Wahle, Brad; Bomann, Werner; Ahr, Hans-Jurgen

    2004-01-01

    When applied in toxicological studies, the recently developed gene expression profiling techniques using microarrays, which brought forth the new field of toxicogenomics, facilitate the interpretation of a toxic compound's mechanism of action. In this study, we investigated whether genotoxic carcinogens at doses known to induce liver tumors in the 2-year rat bioassay deregulate a common set of genes in a short-term in vivo study and, if so, whether these deregulated genes represent defined biological pathways. Rats were dosed with the four genotoxic hepatocarcinogens dimethylnitrosamine (4 mg/kg/day), 2-nitrofluorene (44 mg/kg/day), aflatoxin B1 (0.24 mg/kg/day), and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK, 20 mg/kg/day). After treatment for up to 14 days, the expression profiles of the livers were analyzed on Affymetrix RG_U34A microarrays. Among the significantly upregulated genes were a set of target genes of the tumor suppressor protein p53, indicating a DNA damage response. Such a response was expected and, therefore, confirmed the validity of our approach. In addition, the gene expression changes suggest a specific detoxification response, the activation of proliferative and survival signaling pathways, and some cell structural changes. These responses were strong throughout the 14 day time course for 2-nitrofluorene and aflatoxin B1; in the case of dimethylnitrosamine and NNK, the effects were weakly detectable at day 1 and then increased with time. For dimethylnitrosamine and aflatoxin B1, which caused observable inflammation in vivo, we found a corresponding upregulation of inflammatory genes at the same time points. Thus, by the toxicogenomic analysis of short-term in vivo studies, we identified genes and pathways commonly deregulated by genotoxic carcinogens, which may be indicative for the early events in tumorigenesis and, thus, predictive of later tumor development. PMID:14600272

  19. Protective effect of cactus cladode extract against cisplatin induced oxidative stress, genotoxicity and apoptosis in balb/c mice: combination with phytochemical composition

    PubMed Central

    2012-01-01

    Background Cis-Platinum (II) (cis-diammine dichloroplatinum; CDDP) is a potent antitumor compound widely used for the treatment of many malignancies. An important side-effect of CDDP is nephrotoxicity. The cytotoxic action of this drug is often thought to induce oxidative stress and be associated with its ability to bind DNA to form CDDP–DNA adducts and apoptosis in kidney cells. In this study, the protective effect of cactus cladode extract (CCE) against CDDP-induced oxidative stress and genotoxicity were investigated in mice. We also looked for levels of malondialdehyde (MDA), catalase activity, superoxide dismutase (SOD) activity, chromosome aberrations (CA) test, SOS Chromotest, expressions of p53, bax and bcl2 in kidney and we also analyzed several parameters of renal function markers toxicity such as serum biochemical analysis. Methods Adult, healthy balb/c (20–25 g) male mice aged of 4–5 weeks were pre-treated by intraperitonial administration of CCE (50 mg/Kg.b.w) for 2 weeks. Control animals were treated 3 days a week for 4 weeks by intraperitonial administration of 100 μg/Kg.b.w CDDP. Animals which treated by CDDP and CCE were divided into two groups: the first group was administrated CCE 2 hours before each treatment with CDDP 3 days a week for 4 weeks. The second group was administrated without pre-treatment with CCE but this extract was administrated 24 hours after each treatment with CDDP 3 days a week for 4 weeks. Results Our results showed that CDDP induced significant alterations in all tested oxidative stress markers. In addition it induced CA in bone morrow cells, increased the expression of pro-apoptotic proteins p53 and bax and decreased the expression of anti-apoptotic protein bcl2 in kidney. On the other hand, CDDP significantly increased the levels of urea and creatinine and decreased the levels of albumin and total protein.The treatment of CCE before or after treatment with CDDP showed, (i) a total reduction

  20. Genotoxic effects of zinc oxide nanoparticles.

    PubMed

    Heim, Julia; Felder, Eva; Tahir, Muhammad Nawaz; Kaltbeitzel, Anke; Heinrich, Ulf Ruediger; Brochhausen, Christoph; Mailänder, Volker; Tremel, Wolfgang; Brieger, Juergen

    2015-05-21

    The potential toxicity of nanoparticles has currently provoked public and scientific discussions, and attempts to develop generally accepted handling procedures for nanoparticles are under way. The investigation of the impact of nanoparticles on human health is overdue and reliable test systems accounting for the special properties of nanomaterials must be developed. Nanoparticular zinc oxide (ZnO) may be internalised through ambient air or the topical application of cosmetics, only to name a few, with unpredictable health effects. Therefore, we analysed the determinants of ZnO nanoparticle (NP) genotoxicity. ZnO NPs (15-18 nm in diameter) were investigated at concentrations of 0.1, 10 and 100 μg mL(-1) using the cell line A549. Internalised NPs were only infrequently detectable by TEM, but strongly increased Zn(2+) levels in the cytoplasm and even more in the nuclear fraction, as measured by atom absorption spectroscopy, indicative of an internalised zinc and nuclear accumulation. We observed a time and dosage dependent reduction of cellular viability after ZnO NP exposure. ZnCl2 exposure to cells induced similar impairments of cellular viability. Complexation of Zn(2+) with diethylene triamine pentaacetic acid (DTPA) resulted in the loss of toxicity of NPs, indicating the relevant role of Zn(2+) for ZnO NP toxicity. Foci analyses showed the induction of DNA double strand breaks (DSBs) by ZnO NPs and increased intracellular reactive oxygen species (ROS) levels. Treatment of the cells with the ROS scavenger N-acetyl-l-cysteine (NAC) resulted in strongly decreased intracellular ROS levels and reduced DNA damage. However, a slow increase of ROS after ZnO NP exposure and reduced but not quashed DSBs after NAC-treatment suggest that Zn(2+) may exert genotoxic activities without the necessity of preceding ROS-induction. Our data indicate that ZnO NP toxicity is a result of cellular Zn(2+) intake. Subsequently increased ROS-levels cause DNA damage. However, we found

  1. [Bacterial pigment prodigiosin and its genotoxic effects].

    PubMed

    Gur'ianov, I D; Karamova, N S; Iusupova, D V; Gnezdilov, O I; Koshkarova, L A

    2013-01-01

    The prodigiosin preparation was isolated and purified from Serratia marcescens ATCC 9986, using chromatographic methods. The analysis of the preparation by TLC, NMR-spectrometry and mass-spectrometry allowed to confirm the red pigment fraction as the prodigiosin and detect its purity. Originally, the specific features of the toxic and genotoxic effects of prodigiosin and the possibility of induction of mutations by pigment in the cells of Salmonella typhimurium TA 100 (Ames test) and chromosome damage of mammalian erythroblasts have been determined.

  2. Genotoxic effects of zinc oxide nanoparticles

    NASA Astrophysics Data System (ADS)

    Heim, Julia; Felder, Eva; Tahir, Muhammad Nawaz; Kaltbeitzel, Anke; Heinrich, Ulf Ruediger; Brochhausen, Christoph; Mailänder, Volker; Tremel, Wolfgang; Brieger, Juergen

    2015-05-01

    The potential toxicity of nanoparticles has currently provoked public and scientific discussions, and attempts to develop generally accepted handling procedures for nanoparticles are under way. The investigation of the impact of nanoparticles on human health is overdue and reliable test systems accounting for the special properties of nanomaterials must be developed. Nanoparticular zinc oxide (ZnO) may be internalised through ambient air or the topical application of cosmetics, only to name a few, with unpredictable health effects. Therefore, we analysed the determinants of ZnO nanoparticle (NP) genotoxicity. ZnO NPs (15-18 nm in diameter) were investigated at concentrations of 0.1, 10 and 100 μg mL-1 using the cell line A549. Internalised NPs were only infrequently detectable by TEM, but strongly increased Zn2+ levels in the cytoplasm and even more in the nuclear fraction, as measured by atom absorption spectroscopy, indicative of an internalised zinc and nuclear accumulation. We observed a time and dosage dependent reduction of cellular viability after ZnO NP exposure. ZnCl2 exposure to cells induced similar impairments of cellular viability. Complexation of Zn2+ with diethylene triamine pentaacetic acid (DTPA) resulted in the loss of toxicity of NPs, indicating the relevant role of Zn2+ for ZnO NP toxicity. Foci analyses showed the induction of DNA double strand breaks (DSBs) by ZnO NPs and increased intracellular reactive oxygen species (ROS) levels. Treatment of the cells with the ROS scavenger N-acetyl-l-cysteine (NAC) resulted in strongly decreased intracellular ROS levels and reduced DNA damage. However, a slow increase of ROS after ZnO NP exposure and reduced but not quashed DSBs after NAC-treatment suggest that Zn2+ may exert genotoxic activities without the necessity of preceding ROS-induction. Our data indicate that ZnO NP toxicity is a result of cellular Zn2+ intake. Subsequently increased ROS-levels cause DNA damage. However, we found evidence for

  3. Genotoxic effects of zinc oxide nanoparticles

    NASA Astrophysics Data System (ADS)

    Heim, Julia; Felder, Eva; Tahir, Muhammad Nawaz; Kaltbeitzel, Anke; Heinrich, Ulf Ruediger; Brochhausen, Christoph; Mailänder, Volker; Tremel, Wolfgang; Brieger, Juergen

    2015-05-01

    The potential toxicity of nanoparticles has currently provoked public and scientific discussions, and attempts to develop generally accepted handling procedures for nanoparticles are under way. The investigation of the impact of nanoparticles on human health is overdue and reliable test systems accounting for the special properties of nanomaterials must be developed. Nanoparticular zinc oxide (ZnO) may be internalised through ambient air or the topical application of cosmetics, only to name a few, with unpredictable health effects. Therefore, we analysed the determinants of ZnO nanoparticle (NP) genotoxicity. ZnO NPs (15-18 nm in diameter) were investigated at concentrations of 0.1, 10 and 100 μg mL-1 using the cell line A549. Internalised NPs were only infrequently detectable by TEM, but strongly increased Zn2+ levels in the cytoplasm and even more in the nuclear fraction, as measured by atom absorption spectroscopy, indicative of an internalised zinc and nuclear accumulation. We observed a time and dosage dependent reduction of cellular viability after ZnO NP exposure. ZnCl2 exposure to cells induced similar impairments of cellular viability. Complexation of Zn2+ with diethylene triamine pentaacetic acid (DTPA) resulted in the loss of toxicity of NPs, indicating the relevant role of Zn2+ for ZnO NP toxicity. Foci analyses showed the induction of DNA double strand breaks (DSBs) by ZnO NPs and increased intracellular reactive oxygen species (ROS) levels. Treatment of the cells with the ROS scavenger N-acetyl-l-cysteine (NAC) resulted in strongly decreased intracellular ROS levels and reduced DNA damage. However, a slow increase of ROS after ZnO NP exposure and reduced but not quashed DSBs after NAC-treatment suggest that Zn2+ may exert genotoxic activities without the necessity of preceding ROS-induction. Our data indicate that ZnO NP toxicity is a result of cellular Zn2+ intake. Subsequently increased ROS-levels cause DNA damage. However, we found evidence for

  4. Genotoxic effects of sunlight-activated waste waters

    SciTech Connect

    Strniste, G.F.; Chen, D.J.; Okinaka, R.T.

    1981-01-01

    Natural sunlight induces a genotoxic response in cultured CHO cells pre-treated with shale oil retort process water. Near ultraviolet light (NUV) component of the solar spectrum is the apparent radiation responsible for photoactivation. Cultured human skin fibroblasts are acutely sensitive to the genotoxic effects of photoactivated process water. The mutagenic potential of photoactivated process water in human cells is the same as that witnessed for an equivalent killing dose of the potent skin carcinogen FUV. DNA repair processes are involved in modulating genotoxic effects of this photo-induced process. The exact magnitude of the potential health-related and environmental risks resulting from photoactivation of retort process waters and other oil shale by-products is unassessed at this time. Our demonstration that a significant rate of mutation occurs in cultured human cells exposed to high dilutions of process waters and fluences of NUV comparable to that encountered during nominal exposure to sunlight suggests that such assessment is a prerequisite to minimal risk development of our oil shale resources.

  5. Selenium pretreatment attenuates formaldehyde-induced genotoxicity in A549 cell lines.

    PubMed

    Shi, Yu-Qin; Chen, Xin; Dai, Juan; Jiang, Zhong-Fa; Li, Ning; Zhang, Ben-Yan; Zhang, Zhi-Bing

    2014-11-01

    Formaldehyde is a major industrial chemical and has been extensively used in the manufacture of synthetic resins and chemicals. Numerous studies indicate that formaldehyde can induce various genotoxic effects in vitro and in vivo. A recent study indicated that formaldehyde impaired antioxidant cellular defences and enhanced lipid peroxidation. Selenium is an important antioxidant. We hypothesized that reactive oxygen species (ROS) and lipid peroxidation are involved in formaldehyde-induced genotoxicity in human lung cancer cell line, A549 cell line. To test the hypothesis, we investigated the effects of selenium on formaldehyde-induced genotoxicity in A549 cell lines. The results indicated that exposure to formaldehyde showed the induction of DNA-protein cross-links (DPCs). Formaldehyde significantly increased the malondialdehyde levels and decreased the activities of superoxide dismutase and glutathione peroxidase. In addition, the activations of necrosis factor-κB (NF-κB) and activator protein 1 (AP-1) were induced by the formaldehyde treatment. The pretreatment with selenium counteracted the formaldehyde-induced oxidative stress, ameliorated DPCs and attenuated the activation of NF-κB and AP-1 in A549 cell lines. All the results suggested that the pretreatment with selenium attenuated the formaldehyde-induced genotoxicity through its ROS scavenging and anti-DPCs effects in A549 cell lines.

  6. Genotoxicity and endoreduplication inducing activity of the food flavouring eugenol.

    PubMed

    Maralhas, Alexandra; Monteiro, Ana; Martins, Célia; Kranendonk, Michel; Laires, António; Rueff, José; Rodrigues, António S

    2006-05-01

    Eugenol (1-allyl-3-methoxy-4-hydroxybenzene; CAS No. 97-53-0), a compound extracted from clove oil and marjoram, is widely used as a food flavouring substance and is present in spices such as basil, cinnamon and nutmeg. It is also used in dentistry as an antiseptic and analgesic. Structural similarities with the class IIB IARC carcinogen safrole raises questions on its putative carcinogenicity. We evaluated the genotoxicity of eugenol in V79 cells using chromosomal aberrations (CAs), with and without rat liver biotransformation (S9). Eugenol induced CAs, with significant increases (3.5% aberrant cells) at 2500 microM, demonstrating cytotoxicity at higher doses. S9 increased the induction of CAs in a dose-dependent manner to 15% at 2500 microM, with a high frequency of chromatid exchanges. In particular, an increase of endoreduplicated cells was observed, from 0% at control levels to 2.3 and 5% at 2000 microM, without and with S9, respectively. Since endoreduplication has been linked to inhibition of topoisomerase II, the topoisomerase II inhibitor ICRF-193 was used as a control inducer of endoreduplication (0.1-0.5 microM), increasing the number of endoreduplicated cells from 0% (control) to 3.5% (0.5 microM). S9 did not influence endoreduplication by ICRF-193. Both eugenol and ICRF-193 were also assayed for inhibition of topoisomerase II, and both showed a dose-dependent inhibitory effect, with ICRF-193 being a more potent inhibitor. Our results confirm that eugenol is genotoxic and raises the possibility of it having topoisomerase II inhibiting activity. PMID:16595588

  7. DNA melting and genotoxicity induced by silver nanoparticles and graphene.

    PubMed

    Ivask, Angela; Voelcker, Nicolas H; Seabrook, Shane A; Hor, Maryam; Kirby, Jason K; Fenech, Michael; Davis, Thomas P; Ke, Pu Chun

    2015-05-18

    We have revealed a connection between DNA-nanoparticle (NP) binding and in vitro DNA damage induced by citrate- and branched polyethylenimine-coated silver nanoparticles (c-AgNPs and b-AgNPs) as well as graphene oxide (GO) nanosheets. All three types of nanostructures triggered an early onset of DNA melting, where the extent of the melting point shift depends upon both the type and concentration of the NPs. Specifically, at a DNA/NP weight ratio of 1.1/1, the melting temperature of lambda DNA dropped from 94 °C down to 76 °C, 60 °C, and room temperature for GO, c-AgNPs and b-AgNPs, respectively. Consistently, dynamic light scattering revealed that the largest changes in DNA hydrodynamic size were also associated with the binding of b-AgNPs. Upon introduction to cells, b-AgNPs also exhibited the highest cytotoxicity, at the half-maximal inhibitory (IC50) concentrations of 3.2, 2.9, and 5.2 mg/L for B and T-lymphocyte cell lines and primary lymphocytes, compared to the values of 13.4, 12.2, and 12.5 mg/L for c-AgNPs and 331, 251, and 120 mg/L for GO nanosheets, respectively. At cytotoxic concentrations, all NPs elicited elevated genotoxicities via the increased number of micronuclei in the lymphocyte cells. However, b-AgNPs also induced micronuclei at subtoxic concentrations starting from 0.1 mg/L, likely due to their stronger cellular adhesion and internalization, as well as their subsequent interference with normal DNA synthesis or chromosome segregation during the cell cycle. This study facilitates our understanding of the effects of NP chemical composition, surface charge, and morphology on DNA stability and genotoxicity, with implications ranging from nanotoxicology to nanobiotechnology and nanomedicine. PMID:25781053

  8. Protective effects of melatonin-loaded lipid-core nanocapsules on paraquat-induced cytotoxicity and genotoxicity in a pulmonary cell line.

    PubMed

    Charão, Mariele F; Baierle, Marília; Gauer, Bruna; Goethel, Gabriela; Fracasso, Rafael; Paese, Karina; Brucker, Natália; Moro, Angela M; Bubols, Guilherme B; Dias, Bruna B; Matte, Ursula S; Guterres, Silvia S; Pohlmann, Adriana R; Garcia, Solange C

    2015-06-01

    Many acute poisonings lack effective and specific antidotes. Due to both intentional and accidental exposures, paraquat (PQ) causes thousands of deaths annually, especially by pulmonary fibrosis. Melatonin (Mel), when incorporated into lipid-core nanocapsules (Mel-LNC), has enhanced antioxidant properties. The effects of such a formulation have not yet been studied with respect to mitigation of PQ- induced cytotoxicity and DNA damage. Here, we have tested whether Mel-LNC can ameliorate PQ-induced toxicity in the A549 alveolar epithelial cell line. Physicochemical characterization of the formulations was performed. Cellular uptake was measured using nanocapsules marked with rhodamine B. Cell viability was determined by the MTT assay and DNA damage was assessed by the comet assay. The enzyme-modified comet assay with endonuclease III (Endo III) and formamidopyrimidine glycosylase (FPG) were used to investigate oxidative DNA damage. Incubation with culture medium for 24h did not alter the granulometric profile of Mel-LNC formulations. Following treatment (3 and 24h), red fluorescence was detected around the cell nucleus, indicating internalization of the formulation. Melatonin solution (Mel), Mel-LNC, and LNC did not have significant effects on cell viability or DNA damage. Pre-treatment with Mel-LNC enhanced cell viability and showed a remarkable reduction in % DNA in tail compared to the PQ group; this was not observed in cells pre-treated with Mel. PQ induces oxidative DNA damage detected with the enzyme-modified comet assay. Mel-LNC reduced this damage more effectively than did Mel. In summary, Mel-LNC is better than Mel at protecting A549 cells from the cytotoxic and genotoxic effects of PQ. PMID:26046970

  9. INDUCIBLE HEAT SHOCK PROTEIN (HSP70-1) PROTECTS MCF-7 CELLS FROM THE CYTOTOXIC AND GENOTOXIC EFFECTS OF ARSENITE

    EPA Science Inventory

    Heat shock proteins (HSPs) belong to the highly conserved family of stress proteins and are induced following exposure to arsenic. Elevated HSPs protect against cellular damage from heat but it is unclear wether HSP induction alters the damaging effects of environmental chemical ...

  10. The mitigating effect of Citrullus colocynthis (L.) fruit extract against genotoxicity induced by cyclophosphamide in mice bone marrow cells.

    PubMed

    Shokrzadeh, Mohammad; Chabra, Aroona; Naghshvar, Farshad; Ahmadi, Amirhossein

    2013-01-01

    Possible genoprotective effect of Citrullus colocynthis (L.) (CCT) fruits extract against cyclophosphamide- (CP-)induced DNA damage in mice bone marrow cells was evaluated using micronucleus assay, as an index of induced chromosomal damage. Mice were preadministered with different doses of CCT via intraperitoneal injection for 7 consecutive days followed by injection with CP (70 mg/kg b.w.) 1 hr after the last injection of CCT. After 24 hr, mice were scarified to evaluate the frequency of micronucleated polychromatic erythrocytes (MnPCEs). In addition, the number of polychromatic erythrocytes (PCEs) among 1000 normochromatic erythrocytes (NCEs) per animal was recorded to evaluate bone marrow. Pretreatment with CCT significantly reduced the number of MnPCEs induced by CP in bone marrow cells (P < 0.0001). At 200 mg/kg, CCT had a maximum chemoprotective effect and reduced the number of MnPCEs by 6.37-fold and completely normalized the mitotic activity. CCT also led to marked proliferation and hypercellularity of immature myeloid elements after mice were treated with CP and mitigated the bone marrow suppression. Our study revealed that CCT has an antigenotoxic effect against CP-induced oxidative DNA damage in mice. Therefore, it could be used concomitantly as a supplement to protect people undergoing chemotherapy.

  11. Deoxynivalenol induces cytotoxicity and genotoxicity in animal primary cell culture.

    PubMed

    Singh, Shweta; Banerjee, Subham; Chattopadhyay, Pronobesh; Borthakur, Sashin Kumar; Veer, Vijay

    2015-03-01

    Deoxynivalenol (DON), a mycotoxin produced by Fusarium graminearum, is widely found as a contaminant of food. DON is responsible for a wide range of toxic activities, including gastro-intestinal, lymphoid, bone-marrow and cardiotoxicity. But, the complete explorations of toxicity in terms of hepatotoxicity, nephrotoxicity, cytotoxicity and genotoxicity as well have not been documented well. Again, the mechanisms through which DON damages the DNA and promotes cellular toxicity are not well established. Considering the above fact, this research article is focused on the effects of DON-induced toxicities on experimental animal model as well as its effects on cellular level via various toxicological investigations. DON treatment showed cytotoxicity and DNA damage. Further, flow cytometric analysis of hepatocytes showed cellular apoptosis, suggesting that DON-induced hepatotoxicity is, may be partly, mediated by apoptosis. Moreover, significant differences were found in each haematology and clinical chemistry value, either (p > 0.05). No abnormality of any organ was found during histopathological examination. Hence, it can be concluded that DON induces oxidative DNA damage and increases the formation of centromere positive micronuclei due to aneugenic activity. PMID:25578892

  12. Deoxynivalenol induces cytotoxicity and genotoxicity in animal primary cell culture.

    PubMed

    Singh, Shweta; Banerjee, Subham; Chattopadhyay, Pronobesh; Borthakur, Sashin Kumar; Veer, Vijay

    2015-03-01

    Deoxynivalenol (DON), a mycotoxin produced by Fusarium graminearum, is widely found as a contaminant of food. DON is responsible for a wide range of toxic activities, including gastro-intestinal, lymphoid, bone-marrow and cardiotoxicity. But, the complete explorations of toxicity in terms of hepatotoxicity, nephrotoxicity, cytotoxicity and genotoxicity as well have not been documented well. Again, the mechanisms through which DON damages the DNA and promotes cellular toxicity are not well established. Considering the above fact, this research article is focused on the effects of DON-induced toxicities on experimental animal model as well as its effects on cellular level via various toxicological investigations. DON treatment showed cytotoxicity and DNA damage. Further, flow cytometric analysis of hepatocytes showed cellular apoptosis, suggesting that DON-induced hepatotoxicity is, may be partly, mediated by apoptosis. Moreover, significant differences were found in each haematology and clinical chemistry value, either (p > 0.05). No abnormality of any organ was found during histopathological examination. Hence, it can be concluded that DON induces oxidative DNA damage and increases the formation of centromere positive micronuclei due to aneugenic activity.

  13. Anti-genotoxic ability of α-tocopherol and Anthocyanin to counteract fish DNA damage induced by musk xylene.

    PubMed

    Rocco, Lucia; Mottola, Filomena; Santonastaso, Marianna; Saputo, Valentina; Cusano, Elena; Costagliola, Domenico; Suero, Teresa; Pacifico, Severina; Stingo, Vincenzo

    2015-11-01

    Many compounds released into the environment are able to interact with genetic material. The main purpose of genetic toxicology is to investigate the adverse effects of genotoxic molecules such as reduced fitness, changes in gene frequencies and their impact on genetic diversity in populations following genotoxic exposure. However, the ecological effects of many genotoxic compounds remain poorly understood. The aim of this research was to evaluate the genotoxic activity of an artificial musk (musk xylene, MX) and the potential anti-genotoxicity against this chemical compound of two antioxidant substances (α-tocopherol and an anthocyanins enriched extract). The studies were performed both in vivo and in vitro, using the teleost Danio rerio and the DLEC (Dicentrarchus labrax embryonic cells) cell line. We carried out the exposure to these substances at different times. DNA and cell damage and their possible repair were detected by various experimental approaches: DNA strand breaks (Comet Assay), degree of apoptosis (Diffusion Assay) and molecular alterations at the genomic level (RAPD-PCR technique). Data were collected and analyzed for statistical significance using the Student's t test. The results of this study showed that MX exhibited a genotoxic activity even after short exposure times. The anti-genotoxicity experiments evidenced that both α-tocopherol and Anthocyanin were able to contrast the genotoxic effects induced by MX, both in vivo and in vitro.

  14. High-throughput genotoxicity assay identifies antioxidants as inducers of DNA damage response and cell death

    PubMed Central

    Fox, Jennifer T.; Sakamuru, Srilatha; Huang, Ruili; Teneva, Nedelina; Simmons, Steven O.; Xia, Menghang; Tice, Raymond R.; Austin, Christopher P.; Myung, Kyungjae

    2012-01-01

    Human ATAD5 is a biomarker for identifying genotoxic compounds because ATAD5 protein levels increase posttranscriptionally in response to DNA damage. We screened over 4,000 compounds with a cell-based quantitative high-throughput ATAD5-luciferase assay detecting genotoxic compounds. We identified 22 antioxidants, including resveratrol, genistein, and baicalein, that are currently used or investigated for the treatment of cardiovascular disease, type 2 diabetes, osteopenia, osteoporosis, and chronic hepatitis, as well as for antiaging. Treatment of dividing cells with these compounds induced DNA damage and resulted in cell death. Despite their genotoxic effects, resveratrol, genistein, and baicalein did not cause mutagenesis, which is a major side effect of conventional anticancer drugs. Furthermore, resveratrol and genistein killed multidrug-resistant cancer cells. We therefore propose that resveratrol, genistein, and baicalein are attractive candidates for improved chemotherapeutic agents. PMID:22431602

  15. Effects of p53 knockout on ochratoxin A-induced genotoxicity in p53-deficient gpt delta mice.

    PubMed

    Hibi, Daisuke; Kijima, Aki; Suzuki, Yuta; Ishii, Yuji; Jin, Meilan; Sugita-Konishi, Yoshiko; Yanai, Tokuma; Nishikawa, Akiyoshi; Umemura, Takashi

    2013-02-01

    Ochratoxin A (OTA) is a mycotoxin produced by fungal species and is carcinogenic targeting the S3 segment of the renal proximal tubules in rodents. We previously reported that exposure of gpt delta rats to OTA induced both mutations in the red/gam gene (Spi(-)), suggesting large deletion mutations, and fluctuations in genes transcribed by p53 in the kidneys, which were associated with DNA double-strand break (DSB) repair, particularly homologous recombination (HR) repair. In the present study, to investigate the effects of p53 knockout on OTA-induced mutagenicity, apoptosis, and karyomegaly in renal tubular cells, p53-proficient and p53-deficient gpt delta mice were given 1 and 5mg/kg of OTA for 4 weeks. Significant increases in Spi(-) mutant frequencies (MFs) were observed in the kidneys of p53-deficient gpt delta mice given 5 mg/kg of OTA, but not in the kidneys of p53-proficient gpt delta mice given the same dose. There were no changes in gpt MFs in both genotypes of mice treated with OTA. Western blotting analysis demonstrated that p53 protein levels in the kidneys of p53-proficient mice given OTA were significantly increased compared with the control. Incidences of apoptosis and karyomegaly in not only the outer stripe of outer medulla but also the cortex were significantly higher in p53-deficient at 5mg/kg than in p53-proficient gpt delta mice at same dose, which had no change in the cortex, the inner stripe of outer stripe, and the inner medulla. Given that p53 regulates HR repair in DSBs, these results suggest that OTA may promote large deletion mutations in the process of HR repair for DSBs. Additionally, the lower incidence of karyomegaly and apoptosis found in the p53-proficient gpt delta mice suggests that these phenomena may arise from OTA-induced DNA damage.

  16. Protective effects of the flavonoid chrysin against methylmercury-induced genotoxicity and alterations of antioxidant status, in vivo.

    PubMed

    Manzolli, Eduardo Scandinari; Serpeloni, Juliana Mara; Grotto, Denise; Bastos, Jairo Kennup; Antunes, Lusânia Maria Greggi; Barbosa Junior, Fernando; Barcelos, Gustavo Rafael Mazzaron

    2015-01-01

    The use of phytochemicals has been widely used as inexpensive approach for prevention of diseases related to oxidative damage due to its antioxidant properties. One of dietary flavonoids is chrysin (CR), found mainly in passion fruit, honey, and propolis. Methylmercury (MeHg) is a toxic metal whose main toxic mechanism is oxidative damage. Thus, the study aimed to evaluate the antioxidant effects of CR against oxidative damage induced by MeHg in Wistar rats. Animals were treated with MeHg (30 µg/kg/bw) in presence and absence of CR (0.10, 1.0, and 10 mg/kg/bw) by gavage for 45 days. Glutathione (GSH) in blood was quantified spectrophotometrically and for monitoring of DNA damage, comet assay was used in leukocytes and hepatocytes. MeHg led to a significant increase in the formation of comets; when the animals were exposed to the metal in the presence of CR, higher concentrations of CR showed protective effects. Moreover, exposure to MeHg decreased the levels of GSH and GSH levels were restored in the animals that received CR plus MeHg. Taken together the findings of the present work indicate that consumption of flavonoids such as CR may protect humans against the adverse health effects caused by MeHg. PMID:25810809

  17. Mercury-induced genotoxicity in marine diatom (Chaetoceros tenuissimus).

    PubMed

    Sarker, Subhodeep; Desai, Somashekhar R; Verlecar, Xivanand N; Sarker, Munmun Saha; Sarkar, A

    2016-02-01

    In this paper, we present an evaluation of genotoxic responses in marine diatom, Chaetoceros tenuissimus, isolated from Kandla Creek (lat 23.03° N, long 70.22° E), Gujarat, India, in terms of impairment of DNA integrity as a function of their exposure to elevated levels of mercury (Hg) under laboratory conditions. DNA integrity in C. tenuissimus was determined by partial alkaline unwinding assay. To our knowledge, this is the first such genotoxicity study to be conducted on marine diatom cultures towards understanding the relationship between Hg toxicity and DNA damage. Furthermore, we studied the impact of Hg on the growth of C. tenuissimus as a function of their exposure to enhanced levels of Hg in terms of decreasing chlorophyll a (chl a) concentrations. The data show the genotoxic effect of Hg on the growth of C. tenuissimus as well as DNA integrity to a great extent. Based on the results of our investigations, it is suggested that C. tenuissimus can be used as sentinel species for bio-monitoring of pollution due to genotoxic contaminants.

  18. Genetic Evidence for Genotoxic Effect of Entecavir, an Anti-Hepatitis B Virus Nucleotide Analog

    PubMed Central

    Liu, Ying; Hu, Xiaoqing; Takeda, Shunichi; Qing, Yong

    2016-01-01

    Nucleoside analogues (NAs) have been the most frequently used treatment option for chronic hepatitis B patients. However, they may have genotoxic potentials due to their interference with nucleic acid metabolism. Entecavir, a deoxyguanosine analog, is one of the most widely used oral antiviral NAs against hepatitis B virus. It has reported that entecavir gave positive responses in both genotoxicity and carcinogenicity assays. However the genotoxic mechanism of entecavir remains elusive. To evaluate the genotoxic mechanisms, we analyzed the effect of entecavir on a panel of chicken DT40 B-lymphocyte isogenic mutant cell line deficient in DNA repair and damage tolerance pathways. Our results showed that Parp1-/- mutant cells defective in single-strand break (SSB) repair were the most sensitive to entecavir. Brca1-/-, Ubc13-/- and translesion-DNA-synthesis deficient cells including Rad18-/- and Rev3-/- were hypersensitive to entecavir. XPA-/- mutant deficient in nucleotide excision repair was also slightly sensitive to entecavir. γ-H2AX foci forming assay confirmed the existence of DNA damage by entecavir in Parp1-/-, Rad18-/- and Brca1-/- mutants. Karyotype assay further showed entecavir-induced chromosomal aberrations, especially the chromosome gaps in Parp1-/-, Brca1-/-, Rad18-/- and Rev3-/- cells when compared with wild-type cells. These genetic comprehensive studies clearly identified the genotoxic potentials of entecavir and suggested that SSB and postreplication repair pathways may suppress entecavir-induced genotoxicity. PMID:26800464

  19. Genetic Evidence for Genotoxic Effect of Entecavir, an Anti-Hepatitis B Virus Nucleotide Analog.

    PubMed

    Jiang, Lei; Wu, Xiaohua; He, Fang; Liu, Ying; Hu, Xiaoqing; Takeda, Shunichi; Qing, Yong

    2016-01-01

    Nucleoside analogues (NAs) have been the most frequently used treatment option for chronic hepatitis B patients. However, they may have genotoxic potentials due to their interference with nucleic acid metabolism. Entecavir, a deoxyguanosine analog, is one of the most widely used oral antiviral NAs against hepatitis B virus. It has reported that entecavir gave positive responses in both genotoxicity and carcinogenicity assays. However the genotoxic mechanism of entecavir remains elusive. To evaluate the genotoxic mechanisms, we analyzed the effect of entecavir on a panel of chicken DT40 B-lymphocyte isogenic mutant cell line deficient in DNA repair and damage tolerance pathways. Our results showed that Parp1-/- mutant cells defective in single-strand break (SSB) repair were the most sensitive to entecavir. Brca1-/-, Ubc13-/- and translesion-DNA-synthesis deficient cells including Rad18-/- and Rev3-/- were hypersensitive to entecavir. XPA-/- mutant deficient in nucleotide excision repair was also slightly sensitive to entecavir. γ-H2AX foci forming assay confirmed the existence of DNA damage by entecavir in Parp1-/-, Rad18-/- and Brca1-/- mutants. Karyotype assay further showed entecavir-induced chromosomal aberrations, especially the chromosome gaps in Parp1-/-, Brca1-/-, Rad18-/- and Rev3-/- cells when compared with wild-type cells. These genetic comprehensive studies clearly identified the genotoxic potentials of entecavir and suggested that SSB and postreplication repair pathways may suppress entecavir-induced genotoxicity. PMID:26800464

  20. Effect of exposure route, regimen, and duration on benzene-induced genotoxic and cytotoxic bone marrow damage in mice

    SciTech Connect

    Rice, R.R.; Luke, C.A.; Drew, R.T. )

    1989-07-01

    Mice were exposed to benzene for 13 to 14 weeks by inhalation for either 3 or 5 consecutive days per week or by gavage for 5 consecutive days per week. A weekly evaluation of peripheral blood smears for micronucleated (MN) erythrocyte frequencies and for the percentage of polychromatic erythrocytes (PCE) indicated that the induction of MN-PCE by benzene depended on the sex and strain of mice and on the route of exposure, but not on the inhalation regimen or on the exposure duration. The frequency of MN normochromatic erythrocytes (NCE) not only depended on the sex and strain of mice and on the route of exposure, but directly depended on the inhalation regimen and on the exposure duration. Similarly, the extent of erythropoietic depression in benzene-exposed mice was dependent on sex, mouse strain, exposure duration, and route. However, in contrast to the MN-NCE data, the 3 day/week exposure regimen induced a more persistent depression in erythropoiesis than the 5 day/week exposure regimen. Exposure to benzene also induced in mice a significant depression in packed cell volume (PCV) and bone marrow cellularity, the magnitude of which depended on the sex and strain of mice and on the regimen and route of exposure.

  1. Effect of exposure route, regimen, and duration on benzene-induced genotoxic and cytotoxic bone marrow damage in mice.

    PubMed

    Tice, R R; Luke, C A; Drew, R T

    1989-07-01

    Mice were exposed to benzene for 13 to 14 weeks by inhalation for either 3 or 5 consecutive days per week or by gavage for 5 consecutive days per week. A weekly evaluation of peripheral blood smears for micronucleated (MN) erythrocyte frequencies and for the percentage of polychromatic erythrocytes (PCE) indicated that the induction of MN-PCE by benzene depended on the sex and strain of mice and on the route of exposure, but not on the inhalation regimen or on the exposure duration. The frequency of MN normochromatic erythrocytes (NCE) not only depended on the sex and strain of mice and on the route of exposure, but directly depended on the inhalation regimen and on the exposure duration. Similarly, the extent of erythropoietic depression in benzene-exposed mice was dependent on sex, mouse strain, exposure duration, and route. However, in contrast to the MN-NCE data, the 3 day/week exposure regimen induced a more persistent depression in erythropoiesis than the 5 day/week exposure regimen. Exposure to benzene also induced in mice a significant depression in packed cell volume (PCV) and bone marrow cellularity, the magnitude of which depended on the sex and strain of mice and on the regimen and route of exposure.

  2. Argentine folk medicine: genotoxic effects of Chenopodiaceae family.

    PubMed

    Gadano, A B; Gurni, A A; Carballo, M A

    2006-01-16

    Chenopodium ambrosioides L. and Chenopodium multifidum L. (Chenopodiaceae), common name: Paico, are medicinal plants. They are aromatic shrubs growing in South America. For centuries, they have been used due to its medicinal properties. However, there are few reports in literature about the genotoxic effects of these plants. There for, the aim of these work is the evaluation of genetic damage induced by decoction and infusion of this plants which were assayed in different concentrations (1, 10, 100, 1,000 microL extract/mL culture), by addition of the extract to human lymphocyte cell cultures, negative controls were included. The endpoints evaluated were chromosomal aberrations (CA), sister chromatid exchanges (SCE), cell proliferation kinetics (CPK) and mitotic index (MI). The repeated measure analysis of variance was used for statistic evaluation of the results. The results showed: (a) statistical increase in the percentage of cells with CA and in the frequency of SCE when cultures were exposed to both aromatic plants, (b) a decrease in MI of both Paicos assayed, although no modification in the CPK values was observed, (c) no effect was noticed in the analysis of Chenopodium album L., which was used as negative control of the essential oil. These results suggest a cyto and genotoxic effect of Chenopodium ambrosioides and Chenopodium multifidum aqueous extracts related to the essential oil of the plant (as Chenopodium album did not perform).

  3. Argentine folk medicine: genotoxic effects of Chenopodiaceae family.

    PubMed

    Gadano, A B; Gurni, A A; Carballo, M A

    2006-01-16

    Chenopodium ambrosioides L. and Chenopodium multifidum L. (Chenopodiaceae), common name: Paico, are medicinal plants. They are aromatic shrubs growing in South America. For centuries, they have been used due to its medicinal properties. However, there are few reports in literature about the genotoxic effects of these plants. There for, the aim of these work is the evaluation of genetic damage induced by decoction and infusion of this plants which were assayed in different concentrations (1, 10, 100, 1,000 microL extract/mL culture), by addition of the extract to human lymphocyte cell cultures, negative controls were included. The endpoints evaluated were chromosomal aberrations (CA), sister chromatid exchanges (SCE), cell proliferation kinetics (CPK) and mitotic index (MI). The repeated measure analysis of variance was used for statistic evaluation of the results. The results showed: (a) statistical increase in the percentage of cells with CA and in the frequency of SCE when cultures were exposed to both aromatic plants, (b) a decrease in MI of both Paicos assayed, although no modification in the CPK values was observed, (c) no effect was noticed in the analysis of Chenopodium album L., which was used as negative control of the essential oil. These results suggest a cyto and genotoxic effect of Chenopodium ambrosioides and Chenopodium multifidum aqueous extracts related to the essential oil of the plant (as Chenopodium album did not perform). PMID:16219440

  4. Oxidative stress and genotoxicity induced by ketorolac on the common carp Cyprinus carpio.

    PubMed

    Galar-Martínez, M; García-Medina, S; Gómez-Olivan, L M; Pérez-Coyotl, I; Mendoza-Monroy, D J; Arrazola-Morgain, R E

    2016-09-01

    The nonsteroidal anti-inflammatory drug ketorolac is extensively used in the treatment of acute postoperative pain. This pharmaceutical has been found at concentrations of 0.2-60 µg/L in diverse water bodies around the world; however, its effects on aquatic organisms remain unknown. The present study, evaluated the oxidative stress and genotoxicity induced by sublethal concentrations of ketorolac (1 and 60 µg/L) on liver, brain, and blood of the common carp Cyprinus carpio. This toxicant induced oxidative damage (increased lipid peroxidation, hydroperoxide content, and protein carbonyl content) as well as changes in antioxidant status (superoxide dismutase, catalase, and glutathione peroxidase activity) in liver and brain of carp. In blood, ketorolac increased the frequency of micronuclei and is therefore genotoxic for the test species. The effects observed were time and concentration dependent. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1035-1043, 2016.

  5. Oxidative stress and genotoxicity induced by ketorolac on the common carp Cyprinus carpio.

    PubMed

    Galar-Martínez, M; García-Medina, S; Gómez-Olivan, L M; Pérez-Coyotl, I; Mendoza-Monroy, D J; Arrazola-Morgain, R E

    2016-09-01

    The nonsteroidal anti-inflammatory drug ketorolac is extensively used in the treatment of acute postoperative pain. This pharmaceutical has been found at concentrations of 0.2-60 µg/L in diverse water bodies around the world; however, its effects on aquatic organisms remain unknown. The present study, evaluated the oxidative stress and genotoxicity induced by sublethal concentrations of ketorolac (1 and 60 µg/L) on liver, brain, and blood of the common carp Cyprinus carpio. This toxicant induced oxidative damage (increased lipid peroxidation, hydroperoxide content, and protein carbonyl content) as well as changes in antioxidant status (superoxide dismutase, catalase, and glutathione peroxidase activity) in liver and brain of carp. In blood, ketorolac increased the frequency of micronuclei and is therefore genotoxic for the test species. The effects observed were time and concentration dependent. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1035-1043, 2016. PMID:25899151

  6. Glutathione level regulates HNE-induced genotoxicity in human erythroleukemia cells

    SciTech Connect

    Yadav, Umesh C.S.; Ramana, Kota V.; Awasthi, Yogesh C.; Srivastava, Satish K.

    2008-03-01

    4-Hydroxy-trans-2-nonenal (HNE) is one of the most abundant and toxic lipid aldehydes formed during lipid peroxidation by reactive oxygen species. We have investigated the genotoxic effects of HNE and its regulation by cellular glutathione (GSH) levels in human erythroleukemia (K562) cells. Incubation of K562 cells with HNE (5-10 {mu}M) significantly elicited a 3- to 5-fold increased DNA damage in a time- and dose-dependent manner as measured by comet assay. Depletion of GSH in cells by L-buthionine-[S,R]-sulfoximine (BSO) significantly increased HNE-induced DNA damage, whereas supplementation of GSH by incubating the cells with GSH-ethyl ester significantly decreased HNE-induced genotoxicity. Further, overexpression of mGSTA4-4, a HNE-detoxifying GST isozyme, significantly prevented HNE-induced DNA damage in cells, and ablation of GSTA4-4 and aldose reductase with respective siRNAs further augmented HNE-induced DNA damage. These results suggest that the genotoxicity of HNE is highly dependent on cellular GSH/GST/AR levels and favorable modulation of the aldehyde detoxification system may help in controlling the oxidative stress-induced complications.

  7. Genotoxic and antiapoptotic effect of nicotine on human gingival fibroblasts.

    PubMed

    Argentin, Gabriella; Cicchetti, Rosadele

    2004-05-01

    Growing evidence suggests that nicotine, the addictive component of cigarettes, can have a direct role in tumor development by enhancing cell proliferation and impairing apoptotic process in certain types of human cancer cell lines. Since the correlation between apoptosis and DNA damage is already well documented, we investigated the response of human gingival fibroblasts (HGFs) to nicotine exposure by examining its effect on DNA damage induction and apoptotic process in parallel. To assess the genotoxicity of this drug, the cytokinesis-block micronucleus (CBMN) test was performed. Treatment of HGFs with nicotine, at a concentration of 1 microM, caused a statistically significant increase of micronucleus (MN) frequency at the tested time intervals, while no change was detected in cell growth under the same conditions. Furthermore, we found that preincubation of HGFs with 1 microM nicotine strongly attenuated staurosporine (STP)-induced apoptosis. Finally, we found that cultures exposed to nicotine showed an increase of reactive oxygen species, as determined by increased levels of 2,7-dichlorofluorescein (DCF). When cells were prelabeled with N-acetyl-cysteine (NAC), a substrate for glutathione synthesis, and catalase (CAT), the oxygen free radical scavenger, a significant reduction in cytogenetic damage was observed. Thus, for the first time, we report a concomitant genotoxic and antiapoptotic effect of nicotine in HGFs. PMID:14718647

  8. Comparative study of cytotoxic and genotoxic effects induced by herbicide S-metolachlor and its commercial formulation Twin Pack Gold® in human hepatoma (HepG2) cells.

    PubMed

    Nikoloff, Noelia; Escobar, Luciana; Soloneski, Sonia; Larramendy, Marcelo L

    2013-12-01

    The in vitro effects of S-metolachlor and its formulation Twin Pack Gold(®) (96% a.i.) were evaluated in human hepatoma (HepG2) cells. Cytokinesis-blocked micronucleus cytome (CBMN-cyt) and MTT assays as well as Neutral Red uptake were employed for genotoxicity and cytotoxicity evaluation. Activities were tested within the concentration range of 0.25-15 μg/ml S-metolachlor for 24h of exposure. Both compounds rendered a minor reduction in the NDI although not reaching statistical significance. Results demonstrated that the S-metolachlor was not able to induce MNs. On the other hand, 0.5-6 μg/ml Twin Pack Gold(®) increased the frequency of MNs. When cytotoxicity was estimated, S-metolachlor was not able to induce either a reduction of lysosomal or mitochondrial activity. Contrarily, whereas 1-15 μg/ml Twin Pack Gold(®) induced a significant reduction of mitochondrial activity, all tested concentrations of the formulated product induced a significant decrease of lysosomal performance as a function of the concentration of the S-metolachlor-based formulation titrated into cultures. Genotoxicity and cytotoxicity differences obtained with pure S-metolachlor and the commercial S-metolachlor-based formulation indicate that the latter may contain additional unsafe xenobiotics and support the concept of the importance of evaluating not only the active principle but also the commercial formulation when estimating the real hazard from agrochemicals.

  9. Grape seed extract prevents gentamicin-induced nephrotoxicity and genotoxicity in bone marrow cells of mice.

    PubMed

    El-Ashmawy, Ibrahim M; El-Nahas, Abeer F; Salama, Osama M

    2006-09-01

    The protection conferred by grape seed extract against gentamicin-induced nephrotoxicity and bone marrow chromosomal aberrations have been evaluated in adult Swiss albino mice. The activity of reduced glutathione peroxidase (GSH peroxidase), the levels of glutathione (GSH) and lipid peroxidation as malondialdehyde (MDA) in the kidneys homogenates, serum urea and creatinine were measured, and in addition the changes in kidney histology and bone marrow chromosomes were investigated. Gentamicin (80 mg/kg b.wt. intraperitoneally for 2 weeks) induced kidney damage as indicated from a pronounced changes in kidney histology, a significant increase in serum urea and creatinine and MDA content in the kidney homogenate. While the activity of the antioxidant enzyme GSH peroxidase and the level of GSH were significantly decreased. Gentamicin induced genotoxicity indicated by increased the number of aberrant cells and different types of structural chromosomal aberrations (fragment, deletion and ring chromosome) and showed no effect on mitotic activity of the cell. Pretreatment with grape seed extract (7 days) and simultaneously (14 days) with gentamicin significantly protected the kidney tissue by ameliorating its antioxidant activity. Moreover, grape seed extract significantly protected bone marrow chromosomes from gentamicin induced genotoxicity by reducing the total number of aberrant cells, and different types of structural chromosomal aberrations. It could be concluded that grape seed extract acts as a potent antioxidant prevented kidney damage and genotoxicity of bone marrow cells.

  10. Vanadium as a chemoprotectant: effect of vanadium(III)-L-cysteine complex against cyclophosphamide-induced hepatotoxicity and genotoxicity in Swiss albino mice.

    PubMed

    Basu, Abhishek; Bhattacharjee, Arin; Roy, Somnath Singha; Ghosh, Prosenjit; Chakraborty, Pramita; Das, Ila; Bhattacharya, Sudin

    2014-08-01

    Vanadium is an essential micronutrient for living systems and has antioxidant and genoprotective property. In the present study, the protective role of an organovanadium compound vanadium(III)-L-cysteine (VC-III) was evaluated against hepatotoxicity and genotoxicity induced by cyclophosphamide (CP) (25 mg/kg b.w., i.p.) in Swiss albino mice. Treatment with VC-III (1 mg/kg b.w., p.o.) mitigated CP-induced hepatic injury as indicated by reduction in activities of alanine transaminase, aspartate transaminase, alkaline phosphatase by 1.57-, 1.58- and 1.32-fold in concomitant treatment schedule and by 1.83-, 1.77- and 1.45-fold in pretreatment schedule, respectively, and confirmed by histopathological evidences. Parallel to these changes, VC-III ameliorated CP-induced oxidative stress in liver by 1.46-, 1.26-, 1.32- and 1.42-fold in concomitant treatment group and by 1.95-, 1.40-, 1.46- and 1.73-fold in pretreatment group at the level of H2O2, superoxide, nitric oxide and lipid peroxidation, respectively. VC-III also enhanced activities of antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase, glutathione S-transferase and glutathione (reduced) level in mice liver by 1.46-, 1.37-, 1.29-, 1.44- and 1.45-fold in concomitant treatment schedule and by 1.64-, 1.65-, 1.42-, 1.49- and 1.57-fold in pretreatment schedule, respectively. In addition, the organovanadium compound could efficiently attenuate CP-induced chromosomal aberrations, DNA fragmentation and apoptosis in bone marrow cells and DNA damage in lymphocytes by 1.49-, 1.43-, 1.48- and 1.59-fold in concomitant treatment group and by 1.76-, 1.92-, 1.99- and 2.15-fold in pretreatment group, respectively. Thus, the present study showed that VC-III could exert protection against CP-induced hepatotoxicity and genotoxicity.

  11. Protective role of Lactobacillus plantarum A7 against irinotecan-induced genotoxicity

    PubMed Central

    Sepahi, Soheila; Jafarian-Dehkordi, Abbas; Mirlohi, Maryam; Shirani, Kobra; Etebari, Mahmoud

    2016-01-01

    Objective: Irinotecan is a botanical derivative and an anti-cancer drug with cytotoxic and genotoxic effects. The present study evaluated the effect of Lactobacillus plantarum A7 on the genotoxic activity of irinotecan in a hepatocellular carcinoma cell line (HepG2) by comet assay. Materials and Methods: HepG2 were incubated with irinotecan (100 µM), heat-killed cells (0.025 µg/ml) + irinotecan (100 µM), and cell-free supernatants (0.5 and 1 µg/ml) of L. plantarum A7 + irinotecan (100 µM). Phosphate buffered saline (PBS) was used as negative control. Results: Irinotecan was shown to induce DNA damage in HepG2 cells. The results showed that heat-killed cells (0.025 µg/ml) and cell-free supernatants (0.5 and 1 µg/ml) of L. plantarum significantly reduce irinotecan- induced DNA damage. Conclusion: Our results indicate that L. plantarum A7 can decrease the genotoxic effects of irinotecan in HepG2 cells, in vitro. This finding may be supportive for the optimization of therapeutic efficacy in irinotecan treatment. PMID:27462556

  12. Protective role of curcumin against nicotine-induced genotoxicity on rat liver under restricted dietary protein.

    PubMed

    Bandyopadhyaya, Gargi; Sinha, Surajit; Chattopadhyay, Braja Dulal; Chakraborty, Anindita

    2008-07-01

    Nicotine, the well known addictive chemical of tobacco and active medication for several diseases, has proven to be a potential genotoxic compound. Although it is absorbed through lungs with smoking and mainly metabolized in liver, its effect on liver injuries is not clear. This study was designed to evaluate the genotoxicity of nicotine and corresponding the protective role of curcumin against nicotine on liver of female populations particularly who used tobacco but deprived of healthy diet. The effects were investigated by measurement of total DNA concentration of liver tissues and Comet assay of liver tissue DNA damage of female rats maintained under normal and restricted protein diets. Total DNA contents in the liver tissues were observed to decrease more significantly (P<0.001) by nicotine in both dietary conditions. Significant (P<0.01) increase of total DNA content in normal dietary condition and more significant (P<0.001) increase of total DNA content in protein restricted condition of the liver tissues were observed due to curcumin supplementations. Highly significant (P<0.001) DNA damages (37% in normal diet and 56% in protein restricted diet) of the liver tissues were observed due to nicotine treatment. Curcumin reduced the nicotine-induced DNA damage percentage of the liver tissues more significantly (P<0.001) in protein restricted condition. Curcumin proved its potential to function against genotoxic effect by reducing the DNA damage activity of nicotine and minimized the percentage of DNA damage (50-60%) in protein restricted dietary condition. The degree of nicotine-induced genotoxicity therefore can be effectively compensated by the protective effect of curcumin in protein stress condition. PMID:18508046

  13. Catechins are not major components responsible for anti-genotoxic effects of tea extracts against nitroarenes.

    PubMed

    Ohe, T; Marutani, K; Nakase, S

    2001-09-20

    The anti-genotoxic properties of tea leaf extracts were examined in a Salmonella umu-test. Seven non-fermented teas (green tea), one semi-fermented tea (oolong tea), two fermented teas (black tea and Chinese pu er tea) and two other teas were examined for their anti-genotoxic abilities and for their catechins contents. This was to study the relationship between catechins contents and anti-genotoxic activity of various tea leaf extracts. All types of tea extracts showed more potent suppressive effects against umu gene expression of the SOS response in Salmonella typhimurium TA1535/pSK 1002 induced by four nitroarenes (1-nitropyrene, 2-nitrofluorene, 3-nitrofluoranthene and a mixture of 1,6- and 1,8-dinitropyrene) rather than 4-NQO, AF-2 and MNNG. The anti-genotoxic effect of 12 tea leaf extracts on 1-NP, 2-NF, 3-NF and DNP decreased in the order: oolong tea (semi-fermented tea)>black tea (fermented tea)>sencha (non-fermented tea, an ordinary grade green tea)>tocyucya (other tea)>Chinese pu er tea (fermented tea). The amount of catechins (EGC, C, EGCG, EC and ECG) in various teas in decreasing order was non-fermented tea>semi-fermented tea>fermented tea>other tea. A remarkable feature was the effectiveness of black tea and Chinese pu er tea in suppressing the genotoxicity induced by nitroarenes, in spite of the fact that these fermented teas do not have high catechins contents. Statistical analysis showed that no significant (P<0.01) correlation was found between the anti-genotoxicity of tea extracts against nitroarenes and the catechins contents in tea leaf extracts. In further experiment, fractionation of sencha extract by HPLC revealed that anti-genotoxicity of the peak fraction corresponding to catechins accounted for <10% of the total anti-genotoxic activity of sencha extract against for 1-nitropyrene. These results suggest that catechins are not major components responsible for the anti-genotoxic effects of tea leaf extracts against direct-acting nitroarenes

  14. An antidote for imazalil-induced genotoxicity in vitro: the lichen, Dermatocarpon intestiniforme (Körber) Hasse.

    PubMed

    Türkez, H; Aydin, Elanur; Aslan, A

    2012-09-01

    Imazalil (IMA), a commonly used fungicide in both agricultural and clinical domains, is suspected to produce serious toxic effects in vertebrates. In recent years, a number of studies have suggested that lichens might be easily accessible sources of natural drugs that could be used as a possible food supplement. Extensive research is being performed to explore the importance of lichen species, which are known to contain a variety of pharmacological active compounds. In this context, the antigenotoxic effect of aqueous Dermatocarpon intestiniforme (Körber) Hasse. extract (DIE) was studied against the genotoxic damage induced by IMA on cultured human lymphocytes (n = 6) using chromosomal aberration (CA) and micronucleus (MN) as cytogenetic endpoints. Human peripheral lymphocytes were treated in vitro with varying concentrations of DIE (0, 25, 50 and 100 μg/ml), tested in combination with IMA (336 μg/ml). DIE alone were not genotoxic and when combined with IMA treatment, it reduced the frequency of CAs and the rate of MNs. A clear dose-dependent decrease in the genotoxic damage of IMA was observed, suggesting a genoprotective role of DIE. The results of the present study suggest that this plant extract per se does not have a genotoxic potential, but can alleviate the genotoxicity of IMA on cultured human lymphocytes. In conclusion our findings may have an important application for the protection of cultured human lymphocyte from the genetic damage and side effects induced by medical and agricultural chemicals hazardous for people.

  15. Genotoxic effects of boric acid and borax in zebrafish, Danio rerio using alkaline comet assay.

    PubMed

    Gülsoy, Nagihan; Yavas, Cüneyd; Mutlu, Özal

    2015-01-01

    The present study is conducted to determine the potential mechanisms of Boron compounds, boric acid (BA) and borax (BX), on genotoxicity of zebrafish Danio rerio for 24, 48, 72 and 96-hours acute exposure (level:1, 4, 16, 64 mg/l BA and BX) in semi-static bioassay experiment. For that purpose, peripheral erythrocytes were drawn from caudal vein and Comet assay was applied to assess genotoxicity. Acute (96 hours) exposure and high concentrations of boric acid and borax increases % tail DNA and Olive tail moment. Genotoxicity was found for BA as concentration-dependent and BX as concentration and time dependent manner. In general, significant effects (P < 0,05) on both concentrations and exposure times were observed in experimental groups. DNA damage was highest at 96 h and 24 h for all BX and BA concentrations, respectively in peripheral blood of D. rerio. For the first time, our study demonstrates the effect of waterborne BA and BX exposure on genotoxicity at the molecular level, which may contribute to understanding the mechanism of boric acid and borax-induced genotoxicity in fish. PMID:26862320

  16. Genotoxic effects of boric acid and borax in zebrafish, Danio rerio using alkaline comet assay

    PubMed Central

    Gülsoy, Nagihan; Yavas, Cüneyd; Mutlu, Özal

    2015-01-01

    The present study is conducted to determine the potential mechanisms of Boron compounds, boric acid (BA) and borax (BX), on genotoxicity of zebrafish Danio rerio for 24, 48, 72 and 96-hours acute exposure (level:1, 4, 16, 64 mg/l BA and BX) in semi-static bioassay experiment. For that purpose, peripheral erythrocytes were drawn from caudal vein and Comet assay was applied to assess genotoxicity. Acute (96 hours) exposure and high concentrations of boric acid and borax increases % tail DNA and Olive tail moment. Genotoxicity was found for BA as concentration-dependent and BX as concentration and time dependent manner. In general, significant effects (P < 0,05) on both concentrations and exposure times were observed in experimental groups. DNA damage was highest at 96 h and 24 h for all BX and BA concentrations, respectively in peripheral blood of D. rerio. For the first time, our study demonstrates the effect of waterborne BA and BX exposure on genotoxicity at the molecular level, which may contribute to understanding the mechanism of boric acid and borax-induced genotoxicity in fish. PMID:26862320

  17. Genotoxic effects of boric acid and borax in zebrafish, Danio rerio using alkaline comet assay.

    PubMed

    Gülsoy, Nagihan; Yavas, Cüneyd; Mutlu, Özal

    2015-01-01

    The present study is conducted to determine the potential mechanisms of Boron compounds, boric acid (BA) and borax (BX), on genotoxicity of zebrafish Danio rerio for 24, 48, 72 and 96-hours acute exposure (level:1, 4, 16, 64 mg/l BA and BX) in semi-static bioassay experiment. For that purpose, peripheral erythrocytes were drawn from caudal vein and Comet assay was applied to assess genotoxicity. Acute (96 hours) exposure and high concentrations of boric acid and borax increases % tail DNA and Olive tail moment. Genotoxicity was found for BA as concentration-dependent and BX as concentration and time dependent manner. In general, significant effects (P < 0,05) on both concentrations and exposure times were observed in experimental groups. DNA damage was highest at 96 h and 24 h for all BX and BA concentrations, respectively in peripheral blood of D. rerio. For the first time, our study demonstrates the effect of waterborne BA and BX exposure on genotoxicity at the molecular level, which may contribute to understanding the mechanism of boric acid and borax-induced genotoxicity in fish.

  18. Assessment of genotoxic effects of flumorph by the comet assay in mice organs.

    PubMed

    Zhang, T; Zhao, Q; Zhang, Y; Ning, J

    2014-03-01

    The present study investigated the genotoxic effects of flumorph in various organs (brain, liver, spleen, kidney and sperm) of mice. The DNA damage, measured as comet tail length (µm), was determined using the alkaline comet assay. The comet assay is a sensitive assay for the detection of genotoxicity caused by flumorph using mice as a model. Statistically significant increases in comet assay for both dose-dependent and duration-dependent DNA damage were observed in all the organs assessed. The organs exhibited the maximum DNA damage in 96 h at 54 mg/kg body weight. Brain showed maximum DNA damage followed by spleen > kidney > liver > sperm. Our data demonstrated that flumorph had induced systemic genotoxicity in mammals as it caused DNA damage in all tested vital organs, especially in brain and spleen.

  19. Chemopreventive effect and lack of genotoxicity and mutagenicity of the exopolysaccharide botryosphaeran on human lymphocytes.

    PubMed

    Malini, M; Camargo, M S; Hernandes, L C; Vargas-Rechia, C G; Varanda, E A; Barbosa, A M; Dekker, R F H; Matsumoto, S T; Antunes, L M G; Cólus, I M S

    2016-10-01

    Carbohydrate biopolymers of fungal-origin are an important natural resource in the search for new bioagents with therapeutic and nutraceutical potential. In this study the mutagenic, genotoxic, antigenotoxic and antioxidant properties of the fungal exopolysaccharide botryosphaeran, a (1→3)(1→6)-β-D-glucan, from Botryosphaeria rhodina MAMB-05, was evaluated. The mutagenicity was assessed at five concentrations in Salmonella typhimurium by the Ames test. Normal and tumor (Jurkat cells) human T lymphocyte cultures were used to evaluate the genotoxicity and antigenotoxicity (Comet assay) of botryosphaeran alone and in combination with the mutagen methyl methanesulfonate (MMS). The ability of botryosphaeran to reduce the production of reactive oxygen and nitrogen species (RONS) generated by hydrogen peroxide was assessed using the CM-H2DCFDA probe in lymphocyte cultures under different treatment times. None of the evaluated botryosphaeran concentrations were mutagenic in bacteria, nor induced genotoxicity in normal and tumor lymphocytes. Botryosphaeran protected lymphocyte DNA against damage caused by MMS under simultaneous treatment and post-treatment conditions. However, botryosphaeran was not able to reduce the RONS generated by H2O2. Besides the absence of genotoxicity, botryosphaeran exerted a protective effect on human lymphocytes against genotoxic damage caused by MMS. These results are important in the validation of botryosphaeran as a therapeutic agent targeting health promotion. PMID:27387458

  20. Chemopreventive effect and lack of genotoxicity and mutagenicity of the exopolysaccharide botryosphaeran on human lymphocytes.

    PubMed

    Malini, M; Camargo, M S; Hernandes, L C; Vargas-Rechia, C G; Varanda, E A; Barbosa, A M; Dekker, R F H; Matsumoto, S T; Antunes, L M G; Cólus, I M S

    2016-10-01

    Carbohydrate biopolymers of fungal-origin are an important natural resource in the search for new bioagents with therapeutic and nutraceutical potential. In this study the mutagenic, genotoxic, antigenotoxic and antioxidant properties of the fungal exopolysaccharide botryosphaeran, a (1→3)(1→6)-β-D-glucan, from Botryosphaeria rhodina MAMB-05, was evaluated. The mutagenicity was assessed at five concentrations in Salmonella typhimurium by the Ames test. Normal and tumor (Jurkat cells) human T lymphocyte cultures were used to evaluate the genotoxicity and antigenotoxicity (Comet assay) of botryosphaeran alone and in combination with the mutagen methyl methanesulfonate (MMS). The ability of botryosphaeran to reduce the production of reactive oxygen and nitrogen species (RONS) generated by hydrogen peroxide was assessed using the CM-H2DCFDA probe in lymphocyte cultures under different treatment times. None of the evaluated botryosphaeran concentrations were mutagenic in bacteria, nor induced genotoxicity in normal and tumor lymphocytes. Botryosphaeran protected lymphocyte DNA against damage caused by MMS under simultaneous treatment and post-treatment conditions. However, botryosphaeran was not able to reduce the RONS generated by H2O2. Besides the absence of genotoxicity, botryosphaeran exerted a protective effect on human lymphocytes against genotoxic damage caused by MMS. These results are important in the validation of botryosphaeran as a therapeutic agent targeting health promotion.

  1. Epigenetic alterations induced by genotoxic occupational and environmental human chemical carcinogens: A systematic literature review.

    PubMed

    Chappell, Grace; Pogribny, Igor P; Guyton, Kathryn Z; Rusyn, Ivan

    2016-01-01

    Accumulating evidence suggests that epigenetic alterations play an important role in chemically-induced carcinogenesis. Although the epigenome and genome may be equally important in carcinogenicity, the genotoxicity of chemical agents and exposure-related transcriptomic responses have been more thoroughly studied and characterized. To better understand the evidence for epigenetic alterations of human carcinogens, and the potential association with genotoxic endpoints, we conducted a systematic review of published studies of genotoxic carcinogens that reported epigenetic endpoints. Specifically, we searched for publications reporting epigenetic effects for the 28 agents and occupations included in Monograph Volume 100F of the International Agency for the Research on Cancer (IARC) that were classified as "carcinogenic to humans" (Group 1) with strong evidence of genotoxic mechanisms of carcinogenesis. We identified a total of 158 studies that evaluated epigenetic alterations for 12 of these 28 carcinogenic agents and occupations (1,3-butadiene, 4-aminobiphenyl, aflatoxins, benzene, benzidine, benzo[a]pyrene, coke production, formaldehyde, occupational exposure as a painter, sulfur mustard, and vinyl chloride). Aberrant DNA methylation was most commonly studied, followed by altered expression of non-coding RNAs and histone changes (totaling 85, 59 and 25 studies, respectively). For 3 carcinogens (aflatoxins, benzene and benzo[a]pyrene), 10 or more studies reported epigenetic effects. However, epigenetic studies were sparse for the remaining 9 carcinogens; for 4 agents, only 1 or 2 published reports were identified. While further research is needed to better identify carcinogenesis-associated epigenetic perturbations for many potential carcinogens, published reports on specific epigenetic endpoints can be systematically identified and increasingly incorporated in cancer hazard assessments. PMID:27234561

  2. Cytotoxic, mutagenicity, and genotoxicity effects of guanylhydrazone derivatives.

    PubMed

    Pinhatti, Valéria Rodrigues; da Silva, Juliana; Martins, Tales Leandro Costa; Moura, Dinara Jaqueline; Rosa, Renato Moreira; Villela, Izabel; Stopiglia, Cheila Denise Ottonelli; da Silva Santos, Selma; Scroferneker, Maria Lúcia; Machado, Carlos Renato; Saffi, Jenifer; Henriques, João Antonio Pêgas

    2016-08-01

    Several studies have reported that guanylhydrazones display a variety of desirable biological properties, such as antihypertensive, antibacterial, and antimalarial behaviour. They furthermore promote anti-pneumocystosis and anti-trypanosomiasis, exhibit antitumor activity, and show significant cytotoxicity against cancer cell lines. In this work, we have evaluated the cytotoxicity, mutagenicity, and genotoxicity of two guanylhydrazones derivatives, (E)-2-[(2,3-dimethoxyphenyl) methylene] hydrazine carboxymidamide hydrochloride (2,3-DMeB) and (E)-2-[(3,4-dimethoxyphenyl) methylene] hydrazine carboxymidamide hydrochloride (3,4-DMeB), in different biological models. Both 2,3-DMeB and 3,4-DMeB induce weak cytotoxic and mutagenic effects in bacteria and yeast. The genotoxicity of these compounds was determined in a fibroblast cell line (V79) using alkaline comet assay, as well as a modified comet assay with bacterial enzymes formamidopyrimidine DNA-glycosylase (FPG) and endonuclease III (EndoIII). Both guanylhydrazone derivatives induced DNA damage. Treatment of V79 cells with EndoIII and FPG proteins demonstrated a significant effect of 2,3-DMeB and 3,4-DMeB with respect to oxidized bases. In addition, the derivatives induced a significant increase in the frequency of micronucleated cells at high doses. The antifungal and anti-trypanosomal properties of these guanylhydrazone derivatives were also evaluated, and the obtained results suggest that 2,3-DMeB is more effective than 3,4-DMeB. The biological activity of 2,3-DMeB and 3,4-DMeB may thus be related, at least in part, to their oxidative potential, as well as to their ability to interact with DNA. Considering the previously reported in vitro antitumor activity of guanylhydrazone derivatives in combination with the lack of acute toxicity and the fact that DNA damage is only observed at high doses should render both compounds good candidates for in vivo studies on antitumor activity. PMID:27476330

  3. The role of genotoxicity in asbestos-induced mesothelioma: an explanation for the differences in carcinogenic potential among fiber types.

    PubMed

    Barlow, Christy A; Lievense, Laura; Gross, Sherilyn; Ronk, Christopher J; Paustenbach, Dennis J

    2013-08-01

    The mechanism(s) underlying asbestos toxicity associated with the pathogenesis of mesothelioma has been a challenge to unravel for more than 60 years. A significant amount of research has focused on the characteristics of different fiber types and their potential to induce mesothelioma. These mechanistic studies of fiber toxicity have proceeded along two lines: those demonstrating biochemical mechanisms by which fibers induce disease and those investigating human susceptibility. Most recent studies focused on in vitro genotoxic effects induced by asbestos as the mechanism responsible for asbestos-induced disease. Although asbestos exerts a genotoxic effect at certain concentrations in vitro, a positive response in these tests does not indicate that the chemical is likely to produce an increased risk of carcinogenesis in exposed human populations. Thus far, findings from studies on the effects of fiber type in mesothelial cells are seriously flawed by a lack of a dose response relationship. The common limitation of these in vitro experiments is the lack of attention paid to the complexities of the human anatomy, biochemistry and physiology, which make the observed effects in these experimental systems difficult to extrapolate to persons in the workplace. Mechanistic differences between carcinogenic and genotoxic processes indicate why tests for genotoxicity do not provide much insight regarding the ability to predict carcinogenic potential in workers exposed to asbestos doses in the post-Occupational Safety and Health Administration era. This review discusses the existing literature on asbestos-induced genotoxicity and explains why these studies may or may not likely help characterize the dose-response curve at low dose.

  4. Genotoxic and developmental effects in sea urchins are sensitive indicators of effects of genotoxic chemicals

    SciTech Connect

    Anderson, S.L. . Energy and Environment Division); Hose, J.E. . Dept. of Biology); Knezovich, J.P. . Health and Ecological Assessment Division)

    1994-07-01

    Purple sea urchin (Strongylocentrotus purpuratus) gametes and embryos were exposed to three known mutagenic chemicals (phenol, benzidine,and pentachlorophenol) over concentration ranges bracketing the effect levels for fertilization success. Normal development and cytogenetic effects (anaphase aberrations) were assessed after the cultures were allowed to develop for 48 h. Using radiolabeled chemicals, the authors also characterized concentrations in the test water as well as doses in the embryos following 2- and 48-h exposures. The authors observed dose responses for all chemicals and all responses, except for phenol, which showed no significant effect on development. Fertilization success was never the most sensitive end point. anaphase aberrations were the most sensitive response for phenol, with an LOEC of 2.5 mg/L exposure concentration. Anaphase aberrations and development were equivalent in sensitivity for benzidine within the tested dose range, and an LOEC of <0.1 mg/L was observed. Development was the most sensitive reasons for pentachlorophenol (LOEC 1 mg/L). the LOEC values for this study were generally lower than comparable data for aquatic life or human health protection. The authors conclude that genotoxicity and development evaluations should be included in environmental management applications and that tests developed primarily for human health protection do not reliably predict the effects of toxic substances on aquatic life.

  5. Genotoxic and mutagenic effects of guarana (Paullinia cupana) in prokaryotic organisms.

    PubMed

    da Fonseca, C A; Leal, J; Costa, S S; Leitão, A C

    1994-05-01

    Aqueous extracts of Paullinia cupana (guarana), a species that belongs to the Sapindaceae family, were analyzed for the presence of genotoxic activities in bacterial cells. The extracts of guarana were genotoxic as assessed by lysogenic induction in Escherichia coli and they were also able to induce mutagenesis in Salmonella typhimurium. Addition of S9 microsomal fraction, catalase, superoxide dismutase or thiourea counteracted the genotoxic activity of guarana, suggesting that oxygen reactive species play an essential role in the genotoxicity of aqueous guarana extracts. The genotoxic activity in the extracts was related to the presence of a molecular complex formed by caffeine and a flavonoid (catechin or epicatechin) in the presence of potassium.

  6. Protective effect of lactofermented red beetroot juice against aberrant crypt foci formation, genotoxicity of fecal water and oxidative stress induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine in rats model.

    PubMed

    Klewicka, Elżbieta; Nowak, Adriana; Zduńczyk, Zenon; Juśkiewicz, Jerzy; Cukrowska, Bożena

    2012-11-01

    The aim of the study was to investigate the effects of beetroot juice fermented by Lactobacillus brevis 0944 and Lactobacillus paracasei 0920 (FBJ) on carcinogen induction of aberrant crypt foci (ACF) in rat colon. 2-Amino-1-methyl-6-phenylimidazo[4,5-b] pyridine (PhIP) was used as carcinogen, which was administrated intragastrically at a dose of 10 μg/day, every day of the experiment. Additionally, we investigated the cytotoxicity and genotoxicity of fecal water from experimental animals in the Caco-2 cell line, evaluated by MTT test and the comet assay, respectively, as well as by the count of bacteria adhered to colon epithelium assessed by fluorescence in situ hybridization. Oxidative stress in rats was expressed by measuring serum antioxidant status and the level of malondialdehyde in the kidneys and liver. The experimental rats were divided into four groups based on diet type: basal diet, basal diet supplemented with FBJ, basal diet and PhIP treatment, and basal diet supplemented with FBJ and PhIP treatment. FBJ significantly reduced the number of ACF in PhIP-treated rats (from 59 ± 18 to 26 ± 4). Moreover, the number of extensive aberrations (more than 4 crypts in a focus) decreased from 52 ± 18 to 18 ± 4. Fecal water obtained from rats fed with a PhIP-containing diet induced pronounced cytotoxic and genotoxic effects in Caco-2 cells, but FBJ supplementation of the diet abolished these effects. In groups fed dietary PhP and FBJ the latter was found to increase the antioxidant status of serum from 40% to 66% depending on the fraction. Reduced concentration of malondialdehyde was found only in the kidneys of rats fed with PhIP and FBJ. FBJ present in the diet of rats causes a reduction of MDA in the kidneys from 118.7 nmol/g tissue to 100 nmol/g tissue. The presence of FBJ in the diet of rats significantly increased the count of bacteria, including Lactobacillus/Enterococcus and Bacteroides-Prevotella group adhered to colonic epithelium. In conclusion

  7. Potential genotoxic, mutagenic and antimutagenic effects of coffee: a review.

    PubMed

    Nehlig, A; Debry, G

    1994-04-01

    Coffee and caffeine are mutagenic to bacteria and fungi, and in high concentrations they are also mutagenic to mammalian cells in culture. However, the mutagenic effects of coffee disappear when bacteria or mammalian cells are cultured in the presence of liver extracts which contain detoxifying enzymes. In vivo, coffee and caffeine are devoid of mutagenic effects. Coffee and caffeine are able to interact with many other mutagens and their effects are synergistic with X-rays, ultraviolet light and some chemical agents. Caffeine seems to potentiate rather than to induce chromosomal aberrations and also to transform sublethal damage of mutagenic agents into lethal damage. Conversely, coffee and caffeine are also able to inhibit the mutagenic effects of numerous chemicals. These antimutagenic effects depend on the time of administration of coffee as compared to the acting time of the mutagenic agent. In that case, caffeine seems to be able to restore the normal cycle of mitosis and phosphorylation in irradiated cells. Finally, the potential genotoxic and mutagenic effects of the most important constituents of coffee are reviewed. Mutagenicity of caffeine is mainly attributed to chemically reactive components such as aliphatic dicarbonyls. The latter compounds, formed during the roasting process, are mutagenic to bacteria but less to mammalian cells. Hydrogen peroxide is not very active but seems to considerably enhance mutagenic properties of methylglyoxal. Phenolic compounds are not mutagenic but rather anticarcinogenic. Benzopyrene and mutagens formed during pyrolysis are not mutagenic whereas roasting of coffee beans at high temperature generates mutagenic heterocyclic amines. In conclusion, the mutagenic potential of coffee and caffeine has been demonstrated in lower organisms, but usually at doses several orders of magnitude greater than the estimated lethal dose for caffeine in humans. Therefore, the chances of coffee and caffeine consumption in moderate to

  8. Cytotoxic and genotoxic effects of two hair dyes used in the formulation of black color.

    PubMed

    Tafurt-Cardona, Yaliana; Suares-Rocha, Paula; Fernandes, Thaís Cristina Casimiro; Marin-Morales, Maria Aparecida

    2015-12-01

    According to the International Agency for Research on Cancer (IARC), some hair dyes are considered mutagenic and carcinogenic in in vitro assays and exposed human populations. Epidemiological studies indicate that hairdressers occupationally exposed to hair dyes have a higher risk of developing bladder cancer. In Brazil, 26% of the adults use hair dye. In this study, we investigated the toxic effects of two hair dyes, Basic Red 51 (BR51) and Basic Brown 17 (BB17), which are temporary dyes of the azo group (R-N=N-R'), used in the composition of the black hair dye. To this end, MTT and trypan blue assays (cytotoxicity), comet and micronucleus assay (genotoxicity) were applied, with HepG2 cells. For cytotoxic assessment, dyes were tested in serial dilutions, being the highest concentrations those used in the commercial formula for hair dyes. For genotoxic assessment concentrations were selected according to cell viability. Results showed that both dyes induced significant cytotoxic and genotoxic effects in the cells, in concentrations much lower than those used in the commercial formula. Genotoxic effects could be related to the azo structure present in the composition of the dyes, which is known as mutagenic and carcinogenic. These results point to the hazard of the hair dye exposure to human health. PMID:26404083

  9. Cytotoxic and genotoxic effects of two hair dyes used in the formulation of black color.

    PubMed

    Tafurt-Cardona, Yaliana; Suares-Rocha, Paula; Fernandes, Thaís Cristina Casimiro; Marin-Morales, Maria Aparecida

    2015-12-01

    According to the International Agency for Research on Cancer (IARC), some hair dyes are considered mutagenic and carcinogenic in in vitro assays and exposed human populations. Epidemiological studies indicate that hairdressers occupationally exposed to hair dyes have a higher risk of developing bladder cancer. In Brazil, 26% of the adults use hair dye. In this study, we investigated the toxic effects of two hair dyes, Basic Red 51 (BR51) and Basic Brown 17 (BB17), which are temporary dyes of the azo group (R-N=N-R'), used in the composition of the black hair dye. To this end, MTT and trypan blue assays (cytotoxicity), comet and micronucleus assay (genotoxicity) were applied, with HepG2 cells. For cytotoxic assessment, dyes were tested in serial dilutions, being the highest concentrations those used in the commercial formula for hair dyes. For genotoxic assessment concentrations were selected according to cell viability. Results showed that both dyes induced significant cytotoxic and genotoxic effects in the cells, in concentrations much lower than those used in the commercial formula. Genotoxic effects could be related to the azo structure present in the composition of the dyes, which is known as mutagenic and carcinogenic. These results point to the hazard of the hair dye exposure to human health.

  10. Sewage sludge does not induce genotoxicity and carcinogenesis.

    PubMed

    Silva, Paula Regina Pereira; Barbisan, Luis Fernando; Dagli, Maria Lúcia Zaidan; Saldiva, Paulo Hilário Nascimento

    2012-07-01

    Through a series of experiments, the genotoxic/mutagenic and carcinogenic potential of sewage sludge was assessed. Male Wistar rats were randomly assigned to four groups: Group 1 - negative control; Group 2 - liver carcinogenesis initiated by diethylnitrosamine (DEN; 200 mg/kg i.p.); Group 3 and G4-liver carcinogenesis initiated by DEN and fed 10,000 ppm or 50,000 ppm of sewage sludge. The animals were submitted to a 70% partial hepatectomy at the 3(rd) week. Livers were processed for routine histological analysis and immunohistochemistry, in order to detect glutathione S-transferase positive altered hepatocyte foci (GST-P(+) AHF). Peripheral blood samples for the comet assay were obtained from the periorbital plexus immediately prior to sacrificing. Polychromatic erythrocytes (PCEs) were analyzed in femoral bone-marrow smears, and the frequencies of those micronucleated (MNPCEs) registered. There was no sewage-sludge-induced increase in frequency of either DNA damage in peripheral blood leucocytes, or MNPCEs in the femoral bone marrow. Also, there was no increase in the levels of DNA damage, in the frequency of MNPCEs, and in the development of GST-P AHF when compared with the respective control group.

  11. Sewage sludge does not induce genotoxicity and carcinogenesis

    PubMed Central

    Silva, Paula Regina Pereira; Barbisan, Luis Fernando; Dagli, Maria Lúcia Zaidan; Saldiva, Paulo Hilário Nascimento

    2012-01-01

    Through a series of experiments, the genotoxic/mutagenic and carcinogenic potential of sewage sludge was assessed. Male Wistar rats were randomly assigned to four groups: Group 1 - negative control; Group 2 - liver carcinogenesis initiated by diethylnitrosamine (DEN; 200 mg/kg i.p.); Group 3 and G4-liver carcinogenesis initiated by DEN and fed 10,000 ppm or 50,000 ppm of sewage sludge. The animals were submitted to a 70% partial hepatectomy at the 3rd week. Livers were processed for routine histological analysis and immunohistochemistry, in order to detect glutathione S-transferase positive altered hepatocyte foci (GST-P+ AHF). Peripheral blood samples for the comet assay were obtained from the periorbital plexus immediately prior to sacrificing. Polychromatic erythrocytes (PCEs) were analyzed in femoral bone-marrow smears, and the frequencies of those micronucleated (MNPCEs) registered. There was no sewage-sludge-induced increase in frequency of either DNA damage in peripheral blood leucocytes, or MNPCEs in the femoral bone marrow. Also, there was no increase in the levels of DNA damage, in the frequency of MNPCEs, and in the development of GST-P AHF when compared with the respective control group. PMID:23055806

  12. Sensitivity to cadmium-induced genotoxicity in rat testicular cells is associated with minimal expression of the metallothionein gene.

    PubMed

    Shiraishi, N; Hochadel, J F; Coogan, T P; Koropatnick, J; Waalkes, M P

    1995-02-01

    Cadmium is a carcinogenic metal. Although the mechanism of tumor induction is unknown, DNA/metal interactions may be involved. Metallothionein can protect against cadmium toxicity in our previous work it was shown to reduce cadmium genotoxicity in cultured cells. To extend these results, the genotoxicity of cadmium was studied in R2C cells, a rat testicular Leydig cell line. The R2C cells were very sensitive to cadmium-induced single-strand DNA damage (SSD), as measured by alkaline elution. SSD occurred in R2C cells after treatment with 25 and 50 microM CdCl2 for 2 hr. Prior work showed other cells required much higher levels of cadmium (approximately 500 microM) to induce genotoxicity. The genotoxic levels of cadmium (25-50 microM) were not cytotoxic in R2C cells as assessed by a metabolic activity (MTT) assay. Pretreatment of R2C cells with a low cadmium dose (2 microM, 24 hr) had no effect on cadmium-induced SSD, in contrast to prior work in other cells where such pretreatments reduced SSD through metallothionein gene activation. In fact, cadmium or zinc treatments resulted in little or no increase in metallothionein gene expression in R2C cells as determined by Northern blot analysis for metallothionein mRNA using cDNA or oligonucleotide probes and radioimmunoassay for metallothionein protein production. Basal metallothionein mRNA was essentially nondetectable. Induction of a cadmium-binding protein in R2C cells did occur, as determined by Cd-heme assay, but did not induce tolerance to SSD. In vivo, the Leydig cell is a target for cadmium carcinogenicity and its cadmium-binding protein is thought not to be a true metallothionein. These results indicate that R2C cells are sensitive to cadmium-induced genotoxicity and that this sensitivity is associated with minimal expression of the metallothionein gene. PMID:7871536

  13. Early genotoxic response and accumulation induced by waterborne copper, lead, and arsenic in European seabass, Dicentrarchus labrax.

    PubMed

    Canalejo, Antonio; Diaz-de-Alba, Margarita; Granado-Castro, M Dolores; Cordoba, Francisco; Espada-Bellido, Estrella; Galindo-Riaño, M Dolores; Torronteras, Rafael

    2016-02-01

    Cu, Pb, and As, which are among the most abundant metals in the aquatic environment, are also among the most health-threatened by causing diverse cellular injuries. The aim of this study was to assess and compare the potential early induction of genotoxic effects after waterborne Cu, Pb, and As exposure in European seabass, Dicentrarchus labrax, a commercial widely cultured fish, using the micronucleus (MN) assay in peripheral blood erythrocytes. Fish were exposed under laboratory conditions to nominal solutions ranging 0-10 mg/L for 24 and 96 h. Furthermore, actual metal ion concentrations were measured by inductively coupled plasma atomic emission spectroscopy (ICP-AES) or differential pulse anodic stripping voltammetry (DPASV) in water and four fish tissues differentially related to environmental exposition and metal accumulation, i.e. the gills, liver, muscle, and brain. Dose-dependent increases of micronuclei (MNi) frequency were observed after these very short exposures; based on measured metal concentrations in water, the genotoxic effect ordered as Cu > As > Pb. Significant genotoxic effect at 0.009 mg/L Cu, 0.57 mg/L Pb, and 0.01 mg/L As was seen. For Cu and Pb these are only slightly higher, but for As it is notably lower than the USEPA criteria of maximum concentration to prevent acute toxicity in aquatic organisms. Furthermore, genotoxicity was differentially related to metal accumulation. MNi frequency correlated positively with the content of Pb in all the organs, with the content of As in liver and gills and only with the content of Cu in the brain. In conclusion, our findings raised environmental concerns because these depicted a genotoxic potential of Cu, Pb, and As after a very short exposure to low but environmentally relevant concentrations, too close to regulatory thresholds. In addition, the MN test in D. labrax could be considered an early biomarker of genotoxicity induced by these metals in fish.

  14. Genotoxicity induced by a shale oil byproduct in Chinese hamster cells following metabolic activation

    SciTech Connect

    Okinaka, R.T.; Nickols, J.W.; Chen, D.J.; Strniste, G.F.

    1982-01-01

    A process water obtained from a holding tank during the surface retorting of oil shale has been shown to induce a linear dose response of 100 histidine revertants/sub ..mu../1 in the Ames/Salmonella test. The complex mixture has also previously been shown to induce genotoxicity in mammalian cells following activation by near ultraviolet light and natural sunlight. This report focuses on the effects of a particular oil shale retort process water on cultured Chinese hamster cells following metabolic activation by either rat liver homogenate or lethally irradiated but metabolically competent Syrian hamster embryonic cells. Cytotoxic and mutagenic responses induced by the process water and a fractionated sample from it containing the majority of the mutagenic activity (as assessed by the Salmonella test) were measured under conditions designed to optimally measure the mutagenic potency of the promutagen, benzo(a)pyrene. These results suggest a possible discrepancy in the genotoxic potential of this complex mixture when various methods are utilized to measure its potential.

  15. Genotoxic, epigenetic, and transcriptomic effects of tamoxifen in mouse liver.

    PubMed

    de Conti, Aline; Tryndyak, Volodymyr; Churchwell, Mona I; Melnyk, Stepan; Latendresse, John R; Muskhelishvili, Levan; Beland, Frederick A; Pogribny, Igor P

    2014-11-01

    Tamoxifen is a non-steroidal anti-estrogenic drug widely used for the treatment and prevention of breast cancer in women; however, there is evidence that tamoxifen is hepatocarcinogenic in rats, but not in mice. Additionally, it has been reported that tamoxifen may cause non-alcoholic fatty liver disease (NAFLD) in humans and experimental animals. The goals of the present study were to (i) investigate the mechanisms of the resistance of mice to tamoxifen-induced hepatocarcinogenesis, and (ii) clarify effects of tamoxifen on NAFLD-associated liver injury. Feeding female WSB/EiJ mice a 420 p.p.m. tamoxifen-containing diet for 12 weeks resulted in an accumulation of tamoxifen-DNA adducts, (E)-α-(deoxyguanosin-N(2)-yl)-tamoxifen (dG-TAM) and (E)-α-(deoxyguanosin-N(2)-yl)-N-desmethyltamoxifen (dG-DesMeTAM), in the livers. The levels of hepatic dG-TAM and dG-DesMeTAM DNA adducts in tamoxifen-treated mice were 578 and 340 adducts/108 nucleotides, respectively, while the extent of global DNA and repetitive elements methylation and histone modifications did not differ from the values in control mice. Additionally, there was no biochemical or histopathological evidence of NAFLD-associated liver injury in mice treated with tamoxifen. A transcriptomic analysis of differentially expressed genes demonstrated that tamoxifen caused predominantly down-regulation of hepatic lipid metabolism genes accompanied by a distinct over-expression of the lipocalin 13 (Lcn13) and peroxisome proliferator receptor gamma (Pparγ), which may prevent the development of NAFLD. The results of the present study demonstrate that the resistance of mice to tamoxifen-induced liver carcinogenesis may be associated with its ability to induce genotoxic alterations only without affecting the cellular epigenome and an inability of tamoxifen to induce the development of NAFLD.

  16. Genotoxicity induced by saponified coconut oil surfactant in prokaryote systems.

    PubMed

    Petta, Tirzah Braz; de Medeiros, Sílvia Regina Batistuzzo; do Egito, Eryvaldo Sócrates Tabosa; Agnez-Lima, Lucymara Fassarella

    2004-11-01

    Surfactants are amphiphilic substances with special properties and chemical structures that allow a reduction in interfacial tension, which permits an increase in molecule solubilization. The critical micelle concentration (CMC) is an important characteristic of surfactants that determines their aggregate state, which is generally related to its functional mechanism. In this work the genotoxic potential of saponified coconut oil (SCO), a surfactant obtained from Cocos nucifera, was analyzed using prokaryote systems. DNA strand breaks were not observed after treatment of a plasmid with SCO. Negative results were also obtained in the SOS Chromotest using Escherichia coli strains PQ35 and PQ37. A moderate toxicity of SCO was observed after treatment of strain CC104 with a concentration above its CMC, in which micelles were found. Nevertheless, this treatment was not cytotoxic to a CC104mutMmutY strain. Furthermore, in this DNA repair-deficient strain treatment with a SCO dose below its CMC, in which only monomers were found, demonstrated the possibility of an antioxidant effect, since a reduction in spontaneous mutagenesis frequency was observed. Finally, in an Ames test without metabolic activation mutagenicity induction was observed in strains TA100 and TA104 with treatment doses below the CMC. The cytotoxic, antioxidant and mutagenic effects of SCO can be influenced by the aggregational state.

  17. Mutagenic and genotoxic effects of Guelma's urban wastewater, Algeria.

    PubMed

    Tabet, Mouna; Abda, Ahlem; Benouareth, Djamel E; Liman, Recep; Konuk, Muhsin; Khallef, Messaouda; Taher, Ali

    2015-02-01

    Assessment of water pollution and its effect upon river biotic communities and human health is indispensable to develop control and management strategies. In this study, the mutagenicity and genotoxicity of urban wastewater of the city of Guelma in Algeria were examined between April 2012 and April 2013. For this, two biological tests, namely Amesand chromosomal aberrations (CA) test in Allium cepa root tips were employed on the samples collected from five different sampling stages (S1-S5). In Ames test, two strains of Salmonella typhimurium TA98 and TA100 with or without metabolic activation (S9-mix) were used. All water samples were found to be mutagenic to S. typhimurium TA98 with or without S9-mix. A significant decrease in mitotic index (MI) was observed with a decrease in the percentage of cells in the prophase and an increase in the telophase. Main aberrations observed were anaphase bridges, disturbed anaphase-telophase cells, vagrants and stickiness in anaphase-telophase cells. All treatments of wastewater in April 2012, at S5 in July 2012, at S1 and S5 in November 2012, at S5 in February 2013, and at S1 in April 2013 induced CA when compared to the negative control. Some physicochemical parameters and heavy metals (Cd, Pb, and Cu) were also recorded in the samples examined.

  18. Mutagenic and genotoxic effects of Guelma's urban wastewater, Algeria.

    PubMed

    Tabet, Mouna; Abda, Ahlem; Benouareth, Djamel E; Liman, Recep; Konuk, Muhsin; Khallef, Messaouda; Taher, Ali

    2015-02-01

    Assessment of water pollution and its effect upon river biotic communities and human health is indispensable to develop control and management strategies. In this study, the mutagenicity and genotoxicity of urban wastewater of the city of Guelma in Algeria were examined between April 2012 and April 2013. For this, two biological tests, namely Amesand chromosomal aberrations (CA) test in Allium cepa root tips were employed on the samples collected from five different sampling stages (S1-S5). In Ames test, two strains of Salmonella typhimurium TA98 and TA100 with or without metabolic activation (S9-mix) were used. All water samples were found to be mutagenic to S. typhimurium TA98 with or without S9-mix. A significant decrease in mitotic index (MI) was observed with a decrease in the percentage of cells in the prophase and an increase in the telophase. Main aberrations observed were anaphase bridges, disturbed anaphase-telophase cells, vagrants and stickiness in anaphase-telophase cells. All treatments of wastewater in April 2012, at S5 in July 2012, at S1 and S5 in November 2012, at S5 in February 2013, and at S1 in April 2013 induced CA when compared to the negative control. Some physicochemical parameters and heavy metals (Cd, Pb, and Cu) were also recorded in the samples examined. PMID:25632904

  19. Genotoxic effect of substituted phenoxyacetic acids.

    PubMed

    Venkov, P; Topashka-Ancheva, M; Georgieva, M; Alexieva, V; Karanov, E

    2000-11-01

    The potential toxic and mutagenic action of 2,4-dichlorophenoxyacetic acid has been studied in different test systems, and the obtained results range from increased chromosomal damage to no effect at all. We reexamined the effect of this herbicide by simultaneous using three tests based on yeast, transformed hematopoietic, and mouse bone marrow cells. The results obtained demonstrated that 2,4-dichlorophenoxyacetic acid has cytotoxic and mutagenic effects. The positive response of yeast and transformed hematopoietic cells was verified in kinetics and dose-response experiments. The analysis of metaphase chromosomes indicated a statistically proved induction of breaks, deletions, and exchanges after the intraperitoneal administration of 2,4-dichlorophenoxyacetic acid in mice. The study of phenoxyacetic acid and its differently chlorinated derivatives showed that cytotoxicity and mutagenicity are induced by chlorine atoms at position 2 and/or 4 in the benzene ring. The mutagenic effect was abolished by introduction of a third chlorine atom at position 5. Thus 2,4,5-trichlorophenoxyacetic acid was found to have very weak, if any mutagenic effect; however, the herbicide preserved its toxic effect.

  20. Mitigation by vitamin C of the genotoxic effects of nicotine in mice, assessed by the comet assay and micronucleus induction.

    PubMed

    Kahl, Vivian F S; Reyes, Juliana M; Sarmento, Merielen S; da Silva, Juliana

    2012-05-15

    Nicotine has been reported to cause acute toxicity and to present long-term risks, such as chromosomal damage and genetic instability. The genotoxicity of nicotine may be mediated partly by an oxidative mechanism. We have evaluated the effects of the antioxidant vitamin C on nicotine-induced genotoxicity in mice. The comet assay and the micronucleus test were used to assess the effects of nicotine (15mg/kg) at different exposure times (2, 4, and 24h in the comet assay; 24h in the micronucleus test). Pretreatment with vitamin C 24h before nicotine exposure strongly protected mice against nicotine-induced DNA damage. PMID:22331007

  1. Flavan-3-ol compounds prevent pentylenetetrazol-induced oxidative damage in rats without producing mutations and genotoxicity.

    PubMed

    Scola, Gustavo; Scheffel, Thamiris; Gambato, Gabriela; Freitas, Suzana; Dani, Caroline; Funchal, Claudia; Gomez, Rosane; Coitinho, Adriana; Salvador, Mirian

    2013-02-01

    Seizure disorder is a chronic condition in the brain that affects approximately 50 million people worldwide. Oxidative stress plays a crucial role in the pathophysiology of this disorder and can cause neuronal injury. Approximately one in three treated patients suffers from seizures regardless of pharmacological intervention, which results in oxidative damage. The present study aims to investigate the possible protective effect of antioxidant-rich Vitis labrusca extract on pentylenetetrazol-induced oxidative damage in Wistar rats. Possible behavioral alterations, genotoxic and mutagenic effects of the extract were also evaluated. The results showed that V. labrusca extract provides a significant protective effect against oxidative damage to lipids and proteins induced by pentylenetetrazol in the cerebral cortex, cerebellum, hippocampus and liver of rats. Also, the extract did not alter locomotor behavior. Moreover, it was non-genotoxic and non-mutagenic. Our results suggest the possibility of using V. labrusca extract as a therapeutic agent to minimize neuronal damage associated with seizures.

  2. Investigation of antigenotoxic potential of Syzygium cumini extract (SCE) on cyclophosphamide-induced genotoxicity and oxidative stress in mice.

    PubMed

    Tripathi, Pankaj; Patel, Rakesh K; Tripathi, Rina; Kanzariya, Nilesh R

    2013-10-01

    The present study investigated the protective effects of Syzygium cumini extract (SCE; 100 and 200 mg/kg) against genotoxicity and oxidative stress (OS) induced by cyclophosphamide (CP) in mice. Animals were received 14 days pretreatment (oral) of SCE, followed by induction of genotoxicity by CP (40 mg/kg), 24 hours before sacrifice. Mice bone marrow chromosomal aberration assay, micronucleus assay, and sperm abnormality assay were employed for the study. Activities of hepatic antioxidant enzymes were also investigated. Phytochemical investigation was done to determine total phenolic and flavonoid content in SCE. Results showed that CP produced a significant increase in average percentage of aberrant metaphases and chromosomal aberrations (CAs) excluding gap, and micronuclei (MN) formation in polychromatic erythrocytes produced cytotoxicity in mouse bone marrow cells and induced abnormal sperms in a male germ line. CP also markedly inhibited the activities of superoxide dismutase (SOD), catalase (CAT), and reduced glutahione (GSH) and increased malondialdehyde (MDA) content. Pretreatments with SCE significantly inhibited the frequencies of aberrant metaphases, CAs, MN formation, and cytotoxicity in mouse bone marrow cells induced by CP. SCE also produced a significant reduction of abnormal sperm and antagonized the reduction of CP-induced SOD, CAT, and GSH activities and inhibited increased MDA content in the liver. Total phenolic content present in SCE was 24.68%, whereas total flavonoids were calculated as 3.80%. SCE has a protective effect against genotoxicity and OS induced by CP. PMID:23298251

  3. Role of Peltigera rufescens (Weis) Humb. (a lichen) on imazalil-induced genotoxicity: analysis of micronucleus and chromosome aberrations in vitro.

    PubMed

    Türkez, Hasan; Aydin, Elanur; Sişman, Turgay; Aslan, Ali

    2012-07-01

    Imazalil (IMA), a commonly used fungicide in both agricultural and clinical domains, is suspected to produce very serious toxic effects on vertebrates. On the other hand, in recent years, a number of studies have suggested that lichens might be easily accessible sources of natural drugs that could be used as a possible food supplement. Extensive research is being carried out to explore the importance of lichen species, which are known to contain a variety of pharmacological active compounds. In this context, the anti-genotoxic effects of aqueous Peltigera rufescens (Weis) Humb. extracts (PREs) were studied against the genotoxic damage induced by IMA on cultured human lymphocytes using chromosomal aberrations (CAs) and micronucleus (MN) as cytogenetic parameters. Human peripheral lymphocytes were treated in vitro with varying concentrations of PREs (0, 5, 10, 25, 50 and 100 mg/L), tested in combination with IMA (336 mg/L). PREs alone were not genotoxic and when combined with IMA treatment, reduced the frequency of CAs and the rates of MNs. A clear dose-dependent decrease in the genotoxic damage of IMA was observed, suggesting a genoprotective role of P. rufescens extract. The results of the present study indicate that this plant extract per se do not have genotoxic potential but can minimize the genotoxicity of IMA on human lymphocytes in vitro. In conclusion our findings may have an important application for the protection of human lymphocyte from the genetic damage and side effects induced by agricultural and medical chemicals hazardous in people.

  4. Oxidative and genotoxic effects of 900 MHz electromagnetic fields in the earthworm Eisenia fetida.

    PubMed

    Tkalec, Mirta; Stambuk, Anamaria; Srut, Maja; Malarić, Krešimir; Klobučar, Göran I V

    2013-04-01

    Accumulating evidence suggests that exposure to radiofrequency electromagnetic field (RF-EMF) can have various biological effects. In this study the oxidative and genotoxic effects were investigated in earthworms Eisenia fetida exposed in vivo to RF-EMF at the mobile phone frequency (900 MHz). Earthworms were exposed to the homogeneous RF-EMF at field levels of 10, 23, 41 and 120 V m(-1) for a period of 2h using a Gigahertz Transversal Electromagnetic (GTEM) cell. At the field level of 23 V m(-1) the effect of longer exposure (4h) and field modulation (80% AM 1 kHz sinusoidal) was investigated as well. All exposure treatments induced significant genotoxic effect in earthworms coelomocytes detected by the Comet assay, demonstrating DNA damaging capacity of 900 MHz electromagnetic radiation. Field modulation additionally increased the genotoxic effect. Moreover, our results indicated the induction of antioxidant stress response in terms of enhanced catalase and glutathione reductase activity as a result of the RF-EMF exposure, and demonstrated the generation of lipid and protein oxidative damage. Antioxidant responses and the potential of RF-EMF to induce damage to lipids, proteins and DNA differed depending on the field level applied, modulation of the field and duration of E. fetida exposure to 900 MHz electromagnetic radiation. Nature of detected DNA lesions and oxidative stress as the mechanism of action for the induction of DNA damage are discussed.

  5. Differential modifying effects of food additive butylated hydroxytoluene toward radiation and 4-nitro-quinoline 1-oxide-induced genotoxicity in yeast.

    PubMed

    Anjaria, Kshiti B; Bhat, Nagesh N; Shirsath, Kapil B; Sreedevi, B

    2011-01-01

    The modifying effect of butylated hydroxytoluene (BHT) on 60Co gamma radiation and 4-nitro-quinoline 1-oxide-induced gene conversion and back mutation frequencies was investigated using diploid yeast Saccharomyces cerevisiae D7. Cells were exposed to 100 or 400 Gy in the presence of 0.025-0.25 mM BHT. BHT exhibited radioprotection and significantly reduced radiation-induced gene conversion and back mutation frequencies as well as cell killing. In another set of experiments, cells were simultaneously treated with 0.025-0.1 mM BHT and 0.5 μM 4-NQO. BHT significantly enhanced 4-NQO-induced gene conversion and back mutation frequencies. BHT post-treatment did not modify radiation-induced genetic events but enhanced 4-NQO-induced back mutation frequencies, indicating its potential to act as a tumor-promoting agent with 4-NQO.

  6. Dry olive leaf extract counteracts L-thyroxine-induced genotoxicity in human peripheral blood leukocytes in vitro.

    PubMed

    Topalović, Dijana Žukovec; Živković, Lada; Čabarkapa, Andrea; Djelić, Ninoslav; Bajić, Vladan; Dekanski, Dragana; Spremo-Potparević, Biljana

    2015-01-01

    The thyroid hormones change the rate of basal metabolism, modulating the consumption of oxygen and causing production of reactive oxygen species, which leads to the development of oxidative stress and DNA strand breaks. Olive (Olea europaea L.) leaf contains many potentially bioactive compounds, making it one of the most potent natural antioxidants. The objective of this study was to evaluate the genotoxicity of L-thyroxine and to investigate antioxidative and antigenotoxic potential of the standardized oleuropein-rich dry olive leaf extract (DOLE) against hydrogen peroxide and L-thyroxine-induced DNA damage in human peripheral blood leukocytes by using the comet assay. Various concentrations of the extract were tested with both DNA damage inducers, under two different experimental conditions, pretreatment and posttreatment. Results indicate that L-thyroxine exhibited genotoxic effect and that DOLE displayed protective effect against thyroxine-induced genotoxicity. The number of cells with DNA damage, was significantly reduced, in both pretreated and posttreated samples (P < 0.05). Comparing the beneficial effect of all tested concentrations of DOLE, in both experimental protocols, it appears that extract was more effective in reducing DNA damage in the pretreatment, exhibiting protective role against L-thyroxine effect. This feature of DOLE can be explained by its capacity to act as potent free radical scavenger.

  7. Chlorpyrifos-based insecticides induced genotoxic and cytotoxic effects in the ten spotted live-bearer fish, Cnesterodon decemmaculatus (Jenyns, 1842).

    PubMed

    Vera-Candioti, Josefina; Soloneski, Sonia; Larramendy, Marcelo L

    2014-12-01

    Mortality, genotoxicity, and cytotoxicity of the 48% chlorpyrifos (CPF)-based formulations Lorsban* 48E(®) and CPF Zamba(®) were evaluated on Cnesterodon decemmaculatus (Jenyns, 1842) (Pisces, Poeciliidae) under laboratory conditions. Induction of micronucleus (MN) and alterations in the erythrocyte/erythroblast frequencies were employed as end points for genotoxicity and cytotoxicity, respectively. For Lorsban* 48E(®) , mean values of 0.13 and 0.03 mg/L were determined for LC50 at 24 and 96 h, respectively, and these concentrations reached mean values of 0.40 and 0.21 mg/L for CPF Zamba(®) . Mortality values increased as a positive linear function of the CPF Zamba(®) concentrations, but not for Lorsban* 48E(®) concentrations. There was no significant relationship between mortality and exposure time within the 0-96 h period for both formulations. LC50 values indicated that the fish were seven fold more sensitive to Lorsban* 48E(®) than to CPF Zamba(®) . Lorsban* 48E(®) within the concentration range of 0.008-0.025 mg/L increased MN frequency at both 48 and 96 h of treatment. Similar results were also observed when fish were exposed to 0.052-0.155 mg/L of CPF Zamba(®) , regardless of the exposure time. Cellular cytotoxicity was found after Lorsban* 48E(®) and CPF Zamba(®) treatments for all concentrations and time exposures, estimated by a decrease in the frequency of mature erythrocytes and a concomitant enhanced frequency of erythroblasts in circulating blood. Furthermore, our results demonstrated that Lorsban* 48E(®) and CPF Zamba(®) should be considered as CPF-based commercial formulations with marked genotoxic and cytotoxic properties.

  8. Capsaicin-induced genotoxic stress does not promote apoptosis in A549 human lung and DU145 prostate cancer cells.

    PubMed

    Lewinska, Anna; Jarosz, Paulina; Czech, Joanna; Rzeszutek, Iwona; Bielak-Zmijewska, Anna; Grabowska, Wioleta; Wnuk, Maciej

    2015-02-01

    Capsaicin is the major pungent component of the hot chili peppers of the genus Capsicum, which are consumed worldwide as a food additive. More recently, the selective action of capsaicin against cancer cells has been reported. Capsaicin was found to induce apoptosis and inhibit proliferation of a wide range of cancer cells in vitro, whereas being inactive against normal cells. As data on capsaicin-induced genotoxicity are limited and the effects of capsaicin against human lung A549 and DU145 prostate cancer cells were not explored in detail, we were interested in determining whether capsaicin-associated genotoxicity may also provoke A549 and DU145 cell death. Capsaicin-induced decrease in metabolic activity and cell proliferation, and changes in the cell cycle were limited to high concentrations used (≥ 100 μM), whereas, at lower concentrations, capsaicin stimulated both DNA double strand breaks and micronuclei production. Capsaicin was unable to provoke apoptotic cell death when used up to 250 μM concentrations. Capsaicin induced oxidative stress, but was ineffective in provoking the dissipation of the mitochondrial inner transmembrane potential. A different magnitude of p53 binding protein 1 (53BP1) recruitment contributed to diverse capsaicin-induced genotoxic effects in DU145 and A549 cells. Capsaicin was also found to be a DNA hypermethylating agent in A549 cells. In summary, we have shown that genotoxic effects of capsaicin may contribute to limited susceptibility of DU145 and A549 cancer cells to apoptosis in vitro, which may question the usefulness of capsaicin-based anticancer therapy, at least in a case of lung and prostate cancer. PMID:25813723

  9. Capsaicin-induced genotoxic stress does not promote apoptosis in A549 human lung and DU145 prostate cancer cells.

    PubMed

    Lewinska, Anna; Jarosz, Paulina; Czech, Joanna; Rzeszutek, Iwona; Bielak-Zmijewska, Anna; Grabowska, Wioleta; Wnuk, Maciej

    2015-02-01

    Capsaicin is the major pungent component of the hot chili peppers of the genus Capsicum, which are consumed worldwide as a food additive. More recently, the selective action of capsaicin against cancer cells has been reported. Capsaicin was found to induce apoptosis and inhibit proliferation of a wide range of cancer cells in vitro, whereas being inactive against normal cells. As data on capsaicin-induced genotoxicity are limited and the effects of capsaicin against human lung A549 and DU145 prostate cancer cells were not explored in detail, we were interested in determining whether capsaicin-associated genotoxicity may also provoke A549 and DU145 cell death. Capsaicin-induced decrease in metabolic activity and cell proliferation, and changes in the cell cycle were limited to high concentrations used (≥ 100 μM), whereas, at lower concentrations, capsaicin stimulated both DNA double strand breaks and micronuclei production. Capsaicin was unable to provoke apoptotic cell death when used up to 250 μM concentrations. Capsaicin induced oxidative stress, but was ineffective in provoking the dissipation of the mitochondrial inner transmembrane potential. A different magnitude of p53 binding protein 1 (53BP1) recruitment contributed to diverse capsaicin-induced genotoxic effects in DU145 and A549 cells. Capsaicin was also found to be a DNA hypermethylating agent in A549 cells. In summary, we have shown that genotoxic effects of capsaicin may contribute to limited susceptibility of DU145 and A549 cancer cells to apoptosis in vitro, which may question the usefulness of capsaicin-based anticancer therapy, at least in a case of lung and prostate cancer.

  10. Evaluation of genotoxic effects of the herbicide dicamba using in vivo and in vitro test systems

    SciTech Connect

    Perocco, P.; Ancora, G.; Rani, P.; Valenti, A.M.; Mazzullo, M.; Colacci, A.; Grilli, S. )

    1990-01-01

    The genotoxic effects of the herbicide dicamba have been studied by measuring (1) the unwinding rate of liver DNA from intraperitoneally treated rats (fluorimetric assay); (2) DNA repair as unscheduled DNA synthesis (UDS) induced in cultured human peripheral blood lymphocytes (HPBL); and (3) sister chromatid exchanges (SCE) in HPBL. Results show that dicamba is capable of inducing DNA damage since it significantly increases the unwinding rate of rat liver DNA in vivo and also induces UDS in HPBL in vitro in the presence of exogenous metabolic activation (S-9 mix). Furthermore, dicamba causes a very slight increase in SCE frequency in HPBL in vitro.

  11. Arsenic-Induced Genotoxicity and Genetic Susceptibility to Arsenic-Related Pathologies

    PubMed Central

    Faita, Francesca; Cori, Liliana; Bianchi, Fabrizio; Andreassi, Maria Grazia

    2013-01-01

    The arsenic (As) exposure represents an important problem in many parts of the World. Indeed, it is estimated that over 100 million individuals are exposed to arsenic, mainly through a contamination of groundwaters. Chronic exposure to As is associated with adverse effects on human health such as cancers, cardiovascular diseases, neurological diseases and the rate of morbidity and mortality in populations exposed is alarming. The purpose of this review is to summarize the genotoxic effects of As in the cells as well as to discuss the importance of signaling and repair of arsenic-induced DNA damage. The current knowledge of specific polymorphisms in candidate genes that confer susceptibility to arsenic exposure is also reviewed. We also discuss the perspectives offered by the determination of biological markers of early effect on health, incorporating genetic polymorphisms, with biomarkers for exposure to better evaluate exposure-response clinical relationships as well as to develop novel preventative strategies for arsenic- health effects. PMID:23583964

  12. Genotoxic effects of profenofos on the marine fish, Therapon jarbua.

    PubMed

    Janaki Devi, V; Nagarani, N; Yokesh Babu, M; Vijayalakshimi, N; Kumaraguru, A K

    2012-02-01

    Profenofos (EC(50)) is a persistent and toxic organophosphorus insecticide. Animals get exposed to profenofos via food and water. The present study was designed to explore the genotoxic effect of profenofos in the marine fish. The ubiquitously occurring marine fish, Therapon jarbua, was exposed to profenofos and its effect on DNA was measured using comet (single-cell gel electrophoresis) assay. DNA damage were scored using mean percentage of tail length and compared with the comet classes' viz., 0, 1, 2, 3, and 4. In the first three doses, the (21.5, 43.0 and 86.0 µg L(-1)) comets were observed, of which the mean tail length differed significantly (p < 0.01) from those of unexposed, but not from each other. The mean tail length values were significantly (p < 0.05) higher in gill than in matured erythrocytes. The result indicates that DNA strand breaks in T. jarbua were due to the genotoxic potential of profenofos. From the study, we suggest that T. jarbua may be used as an indicator organism to assess the genotoxic risks of profenofos contamination in marine environments using Comet assay as an identification tool. We infer that organophosphorus insecticides may be dangerous to the marine lives. PMID:21859359

  13. Investigation of antimutagenic potential of Foeniculum vulgare essential oil on cyclophosphamide induced genotoxicity and oxidative stress in mice.

    PubMed

    Tripathi, Pankaj; Tripathi, Rina; Patel, Rakesh K; Pancholi, Shyam S

    2013-01-01

    The present study investigated the protective effects of Foeniculum vulgare (fennel) essential oil (FEO) against genotoxicity induced by cyclophosphamide (CP). Mice bone marrow chromosomal aberration (CA), micronucleus, and sperm abnormality assays were employed to measure genotoxicity and cytotoxicity, respectively. The activities of superoxide dismutase (SOD), glutathione (GSH), catalase (CAT), and malondialdehyde (MDA) content in the liver were also investigated spectrophotometrically. Animals were administered two different doses of FEO (1 and 2 mL/kg) continuously for 3 days at intervals of 24 hours by the oral route before tissue sampling. The results showed that CP produced a significant increase in the average percentage of aberrant metaphases and CAs, excluding gap and micronuclei formation in polychromatic erythrocytes (PCEs), produced cytotoxicity in mouse bone marrow cells, and induced abnormal sperms in the male germ line. CP also markedly inhibited the activities of SOD, CAT, and GSH and increased MDA content. Pretreatments with FEO significantly inhibited the frequencies of aberrant metaphases, CAs, micronuclei formation, and cytotoxicity in mouse bone marrow cells induced by CP and also produced a significant reduction of abnormal sperm and antagonized the reduction of CP-induced SOD, CAT, and GSH activities and inhibited increased MDA content in the liver. FEO inhibits genotoxicity and oxidative stress induced by CP.

  14. Genotoxic and biochemical changes in Baccharis trimera induced by coal contamination.

    PubMed

    Menezes, A P S; Da Silva, J; Rossato, R R; Santos, M S; Decker, N; Da Silva, F R; Cruz, C; Dihl, R R; Lehmann, M; Ferraz, A B F

    2015-04-01

    The processing and combustion of coal in thermal power plants release anthropogenic chemicals into the environment. Baccharis trimera is a common plant used in folk medicine that grows readily in soils degraded by coal mining activities. This shrub bioaccumulates metals released into the environment, and thus its consumption may be harmful to health. The purpose of this study was to investigate the phytochemical profile, antioxidant capacity (DPPH), genotoxic (comet assay) and mutagenic potential (CBMN-cyt) in V79 cells of B. trimera aqueous extracts in the coal-mining region of Candiota (Bt-AEC), and in Bagé, a city that does not experience the effects of exposure to coal (Bt-AEB, a reference site). In the comet assay, only Bt-AEC was genotoxic at the highest doses (0.8mg/mL and 1.6mg/mL), compared to the control. For extracts from both areas, mutagenic effects were observed at higher concentrations compared to the control. The cell damage parameters were significantly high in both extracts; however, more striking values were observed for Bt-AEC, up to the dose of 0.8mg/mL. In chemical analysis, no variation was observed in the contents of flavonoids and phenolic compounds, neither the antioxidant activity, which may suggest that DNA damage observed in V79 cells was induced by the presence of coal contaminants absorbed by the plant.

  15. Sodium arsenite induced changes in survival, growth, metamorphosis and genotoxicity in the Indian cricket frog (Rana limnocharis).

    PubMed

    Singha, Utsab; Pandey, Neelam; Boro, Freeman; Giri, Sarbani; Giri, Anirudha; Biswas, Somava

    2014-10-01

    Arsenic contamination of the environment is a matter of great concern. Understanding the effects of arsenic on aquatic life will act as biological early warning system to assess how arsenic could shape the biodiversity in the affected areas. Rapid decline in amphibian population in recent decades is a cause of major concern. Over the years, amphibians have been recognized as excellent bio-indicators of environmental related stress. In the present study, we examined the toxic and genotoxic effects of sodium arsenite in the tadpoles of the Indian cricket frog (Rana limnocharis). Sodium arsenite at different concentrations (0, 50, 100, 200 and 400 μg L(-1)) neither induced lethality nor significantly altered body weight at metamorphosis. However, it accelerated the rate of metamorphosis at higher concentrations, reduced body size (snout-vent length) and induced developmental deformities such as loss of limbs. Besides, at concentration ranges between 100 and 400 μg L(-1), sodium arsenite induced statistically significant genotoxicity at 24, 48, 72 and 96 h of the exposure in a concentration-dependent manner. However, it did not show time effects as the highest frequency was found between 48 and 72 h which remained steady subsequently. The genotoxicity was confirmed by comet assay in the whole blood cells. These findings suggest that arsenic at environmentally relevant concentrations has significant sub-lethal effects on R.limnocharis, which may have long-term fitness consequence to the species and may have similar implications in other aquatic life too.

  16. Genotoxic effects of glyphosate or paraquat on earthworm coelomocytes.

    PubMed

    Muangphra, Ptumporn; Kwankua, Wimon; Gooneratne, Ravi

    2014-06-01

    The potential genotoxicity (nuclear anomalies, damage to single-strand DNA) and pinocytic adherence activity of two (glyphosate-based and paraquat-based) commercial herbicides to earthworm coelomocytes (immune cells in the coelomic cavity) were assessed. Coelomocytes were extracted from earthworms (Pheretima peguana) exposed to concentrations induces both clastogenic and aneugenic effects on earthworm coelomocytes whereas glyphosate causes only aneugenic effects and therefore does not pose a risk of gene mutation in this earthworm.

  17. Carbon black nanoparticle instillation induces sustained inflammation and genotoxicity in mouse lung and liver

    PubMed Central

    2012-01-01

    Background Widespread occupational exposure to carbon black nanoparticles (CBNPs) raises concerns over their safety. CBNPs are genotoxic in vitro but less is known about their genotoxicity in various organs in vivo. Methods We investigated inflammatory and acute phase responses, DNA strand breaks (SB) and oxidatively damaged DNA in C57BL/6 mice 1, 3 and 28 days after a single instillation of 0.018, 0.054 or 0.162 mg Printex 90 CBNPs, alongside sham controls. Bronchoalveolar lavage (BAL) fluid was analyzed for cellular composition. SB in BAL cells, whole lung and liver were assessed using the alkaline comet assay. Formamidopyrimidine DNA glycosylase (FPG) sensitive sites were assessed as an indicator of oxidatively damaged DNA. Pulmonary and hepatic acute phase response was evaluated by Saa3 mRNA real-time quantitative PCR. Results Inflammation was strongest 1 and 3 days post-exposure, and remained elevated for the two highest doses (i.e., 0.054 and 0.162 mg) 28 days post-exposure (P < 0.001). SB were detected in lung at all doses on post-exposure day 1 (P < 0.001) and remained elevated at the two highest doses until day 28 (P < 0.05). BAL cell DNA SB were elevated relative to controls at least at the highest dose on all post-exposure days (P < 0.05). The level of FPG sensitive sites in lung was increased throughout with significant increases occurring on post-exposure days 1 and 3, in comparison to controls (P < 0.001-0.05). SB in liver were detected on post-exposure days 1 (P < 0.001) and 28 (P < 0.001). Polymorphonuclear (PMN) cell counts in BAL correlated strongly with FPG sensitive sites in lung (r = 0.88, P < 0.001), whereas no such correlation was observed with SB (r = 0.52, P = 0.08). CBNP increased the expression of Saa3 mRNA in lung tissue on day 1 (all doses), 3 (all doses) and 28 (0.054 and 0.162 mg), but not in liver. Conclusions Deposition of CBNPs in lung induces inflammatory and genotoxic effects in mouse lung that persist considerably after the

  18. Comparison of the expression profiles induced by genotoxic and nongenotoxic carcinogens in rat liver.

    PubMed

    Ellinger-Ziegelbauer, Heidrun; Stuart, Barry; Wahle, Brad; Bomann, Werner; Ahr, Hans Juergen

    2005-08-01

    Application of recently developed gene expression techniques using microarrays in toxicological studies (toxicogenomics) facilitate the interpretation of a toxic compound's mode of action and may also allow the prediction of selected toxic effects based on gene expression changes. In order to test this hypothesis, we investigated whether carcinogens at doses known to induce liver tumors in the 2-year rat bioassay deregulate characteristic sets of genes in a short term in vivo study and whether these deregulated genes represent defined biological pathways. Male Wistar rats were dosed with the four nongenotoxic hepatocarcinogens methapyrilene (MPy, 60 mg/kg/day), diethylstilbestrol (DES, 10 mg/kg/day), Wy-14643 (Wy, 60 mg/kg/day), and piperonylbutoxide (PBO, 1200 mg/kg/day). After 1, 3, 7, and 14 days, the livers were taken for histopathological evaluation and for analysis of the gene expression profiles on Affymetrix RG_U34A arrays. The expression profile of the four nongenotoxic carcinogens were compared to the profiles of the four genotoxic carcinogens 2-nitrofluorene (2-NF), dimethylnitrosamine (DMN), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and aflatoxin B1 (AB1) from a similar study reported previously. By using statistical and clustering tools characteristically deregulated genes were extracted and functionally classified. Distinct cellular pathways were affected by the nongenotoxic carcinogens compared to the genotoxic carcinogens which at least partly correlated with the two-stage model of carcinogenesis. Characteristic to genotoxic carcinogens were a DNA damage response and the activation of proliferative and survival signaling. Nongenotoxic carcinogens showed responses to oxidative DNA or protein damage, as well as cell cycle progression and signs of regeneration. Many of the gene alterations found with the nongenotoxic carcinogens imply compound-specific mechanisms. Although neither a single gene nor a single pathway will be sufficient to

  19. Testing systems for biologic markers of genotoxic exposure and effect

    SciTech Connect

    Mendelsohn, M.L.

    1986-11-19

    Societal interest in genotoxicity stems from two concerns: the fear of carcinogenesis secondary to somatic mutation; and the fear of birth defects and decreasing genetic fitness secondary to heritable mutation. There is a pressing need to identify agents that can cause these effects, to understand the underlying dose-response relationships, to identify exposed populations, and to estimate both the magnitude of exposure and the risk of adverse health effects in such populations. Biologic markers refer either to evidence in surrogate organisms, or to the expressions of exposure and effect in human populations. 21 refs.

  20. Genotoxic effects of cisplatin in somatic tissue of Drosophila melanogaster

    SciTech Connect

    Katz, A.J.

    1987-01-01

    Third instar larvae of Drosophila melanogaster transdihybrid for mwh and flr were exposed to varying concentrations of cisplatin by feeding on dry media wetted with aqueous solutions of the test compound. Larval feeding continued until pupation, and surviving transdihybrid adults were collected seven days following commencement of feeding. Wings of adults were removed and scored under 400X magnification for the presence of twin spots and single spots comprised of clones of cells possessing malformed wing hairs. Cisplatin was found to induce both twin spots and single spots, and significant linear concentration-response relationships were obtained with respect to the induction of all endpoints. This capacity to induce mitotic exchange in the somatic tissue of Drosophila compares well with the compound's reported ability to induce chromosome breaks in Drosophila germ cells. However, not all compounds possess similar genotoxic profiles in the somatic an germ tissue of Drosophila.

  1. Randomly amplified polymorphic-DNA analysis for detecting genotoxic effects of Boron on maize (Zea mays L.).

    PubMed

    Sakcali, M Serdal; Kekec, Guzin; Uzonur, Irem; Alpsoy, Lokman; Tombuloglu, Huseyin

    2015-08-01

    This study was carried out to investigate the genotoxic effect of boron (B) on maize using randomly amplified polymorphic DNA (RAPD) method. Experimental design was conducted under 0, 5, 10, 25, 50, 100, 125, and 150 ppm B exposures, and physiological changes have revealed a sharp decrease in root growth rates from 28% to 85%, starting from 25 ppm to 150 ppm, respectively. RAPD-polymerase chain reaction (PCR) analysis shows that DNA alterations are clearly observed from beginning to 100 ppm. B-induced inhibition in root growth had a positive correlation with DNA alterations. Total soluble protein, root and stem lengths, and B content analysis in root and leaves encourage these results as a consequence. These preliminary findings reveal that B causes chromosomal aberration and genotoxic effects on maize. Meanwhile, usage of RAPD-PCR technique is a suitable biomarker to detect genotoxic effect of B on maize and other crops for the future.

  2. Multi-walled carbon nanotubes induce cytotoxicity and genotoxicity in human lung epithelial cells.

    PubMed

    Cavallo, Delia; Fanizza, Carla; Ursini, Cinzia Lucia; Casciardi, Stefano; Paba, Emilia; Ciervo, Aureliano; Fresegna, Anna Maria; Maiello, Raffaele; Marcelloni, Anna Maria; Buresti, Giuliana; Tombolini, Francesca; Bellucci, Stefano; Iavicoli, Sergio

    2012-06-01

    The increasing use of nanomaterials in consumer products highlights the importance of understanding their potential toxic effects. We evaluated cytotoxic and genotoxic/oxidative effects induced by commercial multi-walled carbon nanotubes (MWCNTs) on human lung epithelial (A549) cells treated with 5, 10, 40 and 100 µg ml⁻¹ for different exposure times. Scanning electron microscopy (SEM) analysis, MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] and lactate dehydrogenase (LDH) assays were performed to evaluate cytotoxicity. Fpg-modified comet assay was used to evaluate direct-oxidative DNA damage. LDH leakage was detected after 2, 4 and 24 h of exposure and viability reduction was revealed after 24 h. SEM analysis, performed after 4 and 24 h exposure, showed cell surface changes such as lower microvilli density, microvilli structure modifications and the presence of holes in plasma membrane. We found an induction of direct DNA damage after each exposure time and at all concentrations, statistically significant at 10 and 40 µg ml⁻¹ after 2 h, at 5, 10, 100 µg ml⁻¹ after 4 h and at 10 µg ml⁻¹ after 24 h exposure. However, oxidative DNA damage was not found. The results showed an induction of early cytotoxic effects such as loss of membrane integrity, surface morphological changes and MWCNT agglomerate entrance at all concentrations. We also demonstrated the ability of MWCNTs to induce early genotoxicity. This study emphasizes the suitability of our approach to evaluating simultaneously the early response of the cell membrane and DNA to different MWCNT concentrations and exposure times in cells of target organ. The findings contribute to elucidation of the mechanism by which MWCNTs cause toxic effects in an in vitro experimental model.

  3. Acute effects of a prooxidant herbicide on the microalga Chlamydomonas reinhardtii: Screening cytotoxicity and genotoxicity endpoints.

    PubMed

    Esperanza, Marta; Cid, Ángeles; Herrero, Concepción; Rioboo, Carmen

    2015-08-01

    Since recent evidence has demonstrated that many types of chemicals exhibit oxidative and/or genotoxic potential on living organisms, reactive oxygen species (ROS) formation and DNA damage are currently the best accepted paradigms to assess the potential hazardous biological effects of a wide range of contaminants. The goal of this study was to evaluate the sensitivity of different cytotoxicity and genotoxicity responses on the model microalga Chlamydomonas reinhardtii exposed to the prooxidant herbicide paraquat. In addition to the growth endpoint, cell viability, mitochondrial membrane potential and presence of reactive oxygen species (ROS) were assayed as potential markers of cytotoxicity using flow cytometry (FCM). To study the effects of paraquat on C. reinhardtii DNA, several genotoxicity approaches were implemented for the first time in an ecotoxicological study on microalgae. Oxidative DNA base damage was analysed by measuring the oxidative DNA lesion 8-OHdG by FCM. DNA fragmentation was analysed by different methods: comet assay, and cell cycle analysis by FCM, with a particular focus on the presence of subG1-nuclei. Finally, effects on morphology of nuclei were monitored through DAPI staining. The evaluation of these endpoints showed that several physiological and biochemical parameters reacted to oxidative stress disturbances with greater sensitivity than integrative parameters such as growth rates or cell viability. The experiments revealed concentration-dependent cytotoxicity (ROS formation, depolarization of mitochondrial membrane), genotoxicity (oxidative DNA damage, DNA strand breakage, alterations in nuclear morphology), and cell cycle disturbances (subG1-nuclei, decrease of 4N population) in paraquat-treated cells. Overall, the genotoxicity results indicate that the production of ROS caused by exposure to paraquat induces oxidative DNA damage followed by DNA single- and double-strand breaks and cell cycle alterations, possibly leading to apoptosis

  4. Identification of specific mRNA signatures as fingerprints for carcinogenesis in mice induced by genotoxic and nongenotoxic hepatocarcinogens.

    PubMed

    Kossler, Nadine; Matheis, Katja A; Ostenfeldt, Nina; Bach Toft, Dorthe; Dhalluin, Stéphane; Deschl, Ulrich; Kalkuhl, Arno

    2015-02-01

    Long-term rodent carcinogenicity studies for evaluation of chemicals and pharmaceuticals concerning their carcinogenic potential to humans are currently receiving critical revision. Additional data from mechanistic studies can support cancer risk assessment by clarifying the underlying mode of action. In the course of the IMI MARCAR project, a European consortium of EFPIA partners and academics, which aims to identify biomarkers for nongenotoxic carcinogenesis, a toxicogenomic mouse liver database was generated. CD-1 mice were orally treated for 3 and 14 days with 3 known genotoxic hepatocarcinogens: C.I. Direct Black 38, Dimethylnitrosamine and 4,4'-Methylenedianiline; 3 nongenotoxic hepatocarcinogens: 1,4-Dichlorobenzene, Phenobarbital sodium and Piperonyl butoxide; 4 nonhepatocarcinogens: Cefuroxime sodium, Nifedipine, Prazosin hydrochloride and Propranolol hydrochloride; and 3 compounds that show ambiguous results in genotoxicity testing: Cyproterone acetate, Thioacetamide and Wy-14643. By liver mRNA expression analysis using individual animal data, we identified 64 specific biomarker candidates for genotoxic carcinogens and 69 for nongenotoxic carcinogens for male mice at day 15. The majority of genotoxic carcinogen biomarker candidates possess functions in DNA damage response (eg, apoptosis, cell cycle progression, DNA repair). Most of the identified nongenotoxic carcinogen biomarker candidates are involved in regulation of cell cycle progression and apoptosis. The derived biomarker lists were characterized with respect to their dependency on study duration and gender and were successfully used to characterize carcinogens with ambiguous genotoxicity test results, such as Wy-14643. The identified biomarker candidates improve the mechanistic understanding of drug-induced effects on the mouse liver that result in hepatocellular adenomas and/or carcinomas in 2-year mouse carcinogenicity studies.

  5. Early Genotoxic and Cytotoxic Effects of the Toxic Dinoflagellate Prorocentrum lima in the Mussel Mytilus galloprovincialis

    PubMed Central

    Prego-Faraldo, María Verónica; Valdiglesias, Vanessa; Laffon, Blanca; Mendez, Josefina; Eirin-Lopez, Jose M.

    2016-01-01

    Okadaic acid (OA) and dinophysistoxins (DTXs) are the main toxins responsible for diarrhetic shellfish poisoning (DSP) intoxications during harmful algal blooms (HABs). Although the genotoxic and cytotoxic responses to OA have been evaluated in vitro, the in vivo effects of these toxins have not yet been fully explored. The present work fills this gap by evaluating the in vivo effects of the exposure to the DSP-toxin-producing dinoflagellate Prorocentrum lima during the simulation of an early HAB episode in the mussel Mytilus galloprovincialis. The obtained results revealed that in vivo exposure to this toxic microalgae induced early genotoxicity in hemocytes, as a consequence of oxidative DNA damage. In addition, the DNA damage observed in gill cells seems to be mainly influenced by exposure time and P. lima concentration, similarly to the case of the oxidative damage found in hemocytes exposed in vitro to OA. In both cell types, the absence of DNA damage at low toxin concentrations is consistent with the notion suggesting that this level of toxicity does not disturb the antioxidant balance. Lastly, in vivo exposure to growing P. lima cell densities increased apoptosis but not necrosis, probably due to the presence of a high number of protein apoptosis inhibitors in molluscs. Overall, this work sheds light into the in vivo genotoxic and cytotoxic effects of P. lima. In doing so, it also demonstrates for the first time the potential of the modified (OGG1) comet assay for assessing oxidative DNA damage caused by marine toxins in marine invertebrates. PMID:27231936

  6. Early Genotoxic and Cytotoxic Effects of the Toxic Dinoflagellate Prorocentrum lima in the Mussel Mytilus galloprovincialis.

    PubMed

    Prego-Faraldo, María Verónica; Valdiglesias, Vanessa; Laffon, Blanca; Mendez, Josefina; Eirin-Lopez, Jose M

    2016-01-01

    Okadaic acid (OA) and dinophysistoxins (DTXs) are the main toxins responsible for diarrhetic shellfish poisoning (DSP) intoxications during harmful algal blooms (HABs). Although the genotoxic and cytotoxic responses to OA have been evaluated in vitro, the in vivo effects of these toxins have not yet been fully explored. The present work fills this gap by evaluating the in vivo effects of the exposure to the DSP-toxin-producing dinoflagellate Prorocentrum lima during the simulation of an early HAB episode in the mussel Mytilus galloprovincialis. The obtained results revealed that in vivo exposure to this toxic microalgae induced early genotoxicity in hemocytes, as a consequence of oxidative DNA damage. In addition, the DNA damage observed in gill cells seems to be mainly influenced by exposure time and P. lima concentration, similarly to the case of the oxidative damage found in hemocytes exposed in vitro to OA. In both cell types, the absence of DNA damage at low toxin concentrations is consistent with the notion suggesting that this level of toxicity does not disturb the antioxidant balance. Lastly, in vivo exposure to growing P. lima cell densities increased apoptosis but not necrosis, probably due to the presence of a high number of protein apoptosis inhibitors in molluscs. Overall, this work sheds light into the in vivo genotoxic and cytotoxic effects of P. lima. In doing so, it also demonstrates for the first time the potential of the modified (OGG1) comet assay for assessing oxidative DNA damage caused by marine toxins in marine invertebrates. PMID:27231936

  7. Genotoxic effect of ethacrynic acid and impact of antioxidants

    SciTech Connect

    Ward, William M.; Hoffman, Jared D.; Loo, George

    2015-07-01

    It is known that ethacrynic acid (EA) decreases the intracellular levels of glutathione. Whether the anticipated oxidative stress affects the structural integrity of DNA is unknown. Therefore, DNA damage was assessed in EA-treated HCT116 cells, and the impact of several antioxidants was also determined. EA caused both concentration-dependent and time-dependent DNA damage that eventually resulted in cell death. Unexpectedly, the DNA damage caused by EA was intensified by either ascorbic acid or trolox. In contrast, EA-induced DNA damage was reduced by N-acetylcysteine and by the iron chelator, deferoxamine. In elucidating the DNA damage, it was determined that EA increased the production of reactive oxygen species, which was inhibited by N-acetylcysteine and deferoxamine but not by ascorbic acid and trolox. Also, EA decreased glutathione levels, which were inhibited by N-acetylcysteine. But, ascorbic acid, trolox, and deferoxamine neither inhibited nor enhanced the capacity of EA to decrease glutathione. Interestingly, the glutathione synthesis inhibitor, buthionine sulfoxime, lowered glutathione to a similar degree as EA, but no noticeable DNA damage was found. Nevertheless, buthionine sulfoxime potentiated the glutathione-lowering effect of EA and intensified the DNA damage caused by EA. Additionally, in examining redox-sensitive stress gene expression, it was found that EA increased HO-1, GADD153, and p21mRNA expression, in association with increased nuclear localization of Nrf-2 and p53 proteins. In contrast to ascorbic acid, trolox, and deferoxamine, N-acetylcysteine suppressed the EA-induced upregulation of GADD153, although not of HO-1. Overall, it is concluded that EA has genotoxic properties that can be amplified by certain antioxidants. - Highlights: • Ethacrynic acid (EA) caused cellular DNA damage. • EA-induced DNA damage was potentiated by ascorbic acid or trolox. • EA increased ROS production, not inhibited by ascorbic acid or trolox. • EA

  8. Genotoxicity to human cells induced by air particulates isolated during the Kuwait oil fires.

    PubMed

    Kelsey, K T; Xia, F; Bodell, W J; Spengler, J D; Christiani, D C; Dockery, D W; Liber, H L

    1994-01-01

    In an effort to examine the potential of exposure to soot from the 1991 oil fires in the Kuwait desert for inducing genetic effects we studied the in vitro genotoxicity of this material. Air particulates isolated near the Kuwait oil fires were studied using three assays. Dose-dependent increases were observed for both sister chromatid exchanges in human peripheral blood lymphocytes and mutation at the hprt locus in the metabolically competent human lymphoblast cell line AHH-1. Similar magnitudes of response were seen using these two assays when testing a standard air particulate sample which had been isolated from the Washington, DC, area. Using the 32P-postlabeling assay, no increase in DNA adduct formation was observed in AHH-1 cells treated with particulates isolated from sampling in Kuwait.

  9. Genotoxic effects of starvation and dimethoate in haemocytes and midgut gland cells of wolf spider Xerolycosa nemoralis (Lycosidae).

    PubMed

    Wilczek, Grażyna; Mędrzak, Monika; Augustyniak, Maria; Wilczek, Piotr; Stalmach, Monika

    2016-06-01

    The aim of this study was to assess the genotoxic effects of starvation and dimethoate (organophosphate insecticide) in female and male wolf spiders Xerolycosa nemoralis (Lycosidae) exposed to the stressors under laboratory conditions. DNA damage was measured in haemocytes and midgut gland cells using the comet assay. In response to the two stressing factors, both cell types showed %TDNA, tail length (TL) and OTM values higher in males than in females. Level of DNA damage in haemocytes was greater than in midgut gland cells. In both sexes, the strongest genotoxicity was recorded at single application of dimethoate. After five-time exposure to the pesticide, genotoxic effects of a single dose were sustained in males and reduced to the control level in females. Starvation stress was well tolerated by the females, in which neither cell type was affected by DNA damage. However, in male haemocytes food deprivation induced severe DNA damage, what suggests suppression of the defence potential at prolonged starvation periods.

  10. Evolved Cellular Mechanisms to Respond to Genotoxic Insults: Implications for Radiation-Induced Hematologic Malignancies

    PubMed Central

    Fleenor, Courtney J.; Higa, Kelly; Weil, Michael M.; DeGregori, James

    2015-01-01

    Human exposure to ionizing radiation is highly associated with adverse health effects, including reduced hematopoietic cell function and increased risk of carcinogenesis. The hematopoietic deficits manifest across blood cell types and persist for years after radiation exposure, suggesting a long-lived and multi-potent cellular reservoir for radiation-induced effects. As such, research has focused on identifying both the immediate and latent hematopoietic stem cell responses to radiation exposure. Radiation-associated effects on hematopoietic function and malignancy development have generally been attributed to the direct induction of mutations resulting from radiation-induced DNA damage. Other studies have illuminated the role of cellular programs that both limit and enhance radiation-induced tissue phenotypes and carcinogenesis. In this review, distinct but collaborative cellular responses to genotoxic insults are highlighted, with an emphasis on how these programmed responses impact hematopoietic cellular fitness and competition. These radiation-induced cellular programs include apoptosis, senescence and impaired self-renewal within the hematopoietic stem cell (HSC) pool. In the context of sporadic DNA damage to a cell, these cellular responses act in concert to restore tissue function and prevent selection for adaptive oncogenic mutations. But in the contexts of whole-tissue exposure or whole-body exposure to genotoxins, such as radiotherapy or chemotherapy, we propose that these programs can contribute to long-lasting tissue impairment and increased carcinogenesis. PMID:26414506

  11. Evolved Cellular Mechanisms to Respond to Genotoxic Insults: Implications for Radiation-Induced Hematologic Malignancies.

    PubMed

    Fleenor, Courtney J; Higa, Kelly; Weil, Michael M; DeGregori, James

    2015-10-01

    Human exposure to ionizing radiation is highly associated with adverse health effects, including reduced hematopoietic cell function and increased risk of carcinogenesis. The hematopoietic deficits manifest across blood cell types and persist for years after radiation exposure, suggesting a long-lived and multi-potent cellular reservoir for radiation-induced effects. As such, research has focused on identifying both the immediate and latent hematopoietic stem cell responses to radiation exposure. Radiation-associated effects on hematopoietic function and malignancy development have generally been attributed to the direct induction of mutations resulting from radiation-induced DNA damage. Other studies have illuminated the role of cellular programs that both limit and enhance radiation-induced tissue phenotypes and carcinogenesis. In this review, distinct but collaborative cellular responses to genotoxic insults are highlighted, with an emphasis on how these programmed responses impact hematopoietic cellular fitness and competition. These radiation-induced cellular programs include apoptosis, senescence and impaired self-renewal within the hematopoietic stem cell (HSC) pool. In the context of sporadic DNA damage to a cell, these cellular responses act in concert to restore tissue function and prevent selection for adaptive oncogenic mutations. But in the contexts of whole-tissue exposure or whole-body exposure to genotoxins, such as radiotherapy or chemotherapy, we propose that these programs can contribute to long-lasting tissue impairment and increased carcinogenesis. PMID:26414506

  12. Effects of soil pH on the Vicia-micronucleus genotoxicity assay.

    PubMed

    Dhyèvre, Adrien; Foltête, Anne Sophie; Aran, Delphine; Muller, Serge; Cotelle, Sylvie

    2014-11-01

    In the field of contaminated sites and soil management, chemical analyses only bring typological data about pollution. As far as bioavailability and effects on organisms are concerned, we need ecotoxicology tools. In this domain, among many existing tests, we chose to study genotoxicity because it is a short-term endpoint with long-term consequences. The aim of this study is to assess the effects of soil pH on the results of the Vicia faba root tip micronucleus test for the two following reasons: (i) to define the pH range within which the test can be performed without modifying the soil to be tested, within the framework of the ISO standard of the test and (ii) to provides information about the effects of the pH on the genotoxic potential of soils. In this context, we modified the pH of a standard soil with HCl or NaOH and we spiked the matrix with copper (2, 4 and 8 mmol kg(-1) dry soil) or with maleic hydrazide, an antigerminative chemical (5, 10 and 20 μmol kg(-1) dry soil). We concluded that the pH had no effect on the mitotic index or micronucleus frequency in the root cells of the negative controls: extreme pH values did not induce micronucleus formation in root cells. Moreover, according to our results, the Vicia-micronucleus test can be performed with pH values ranging between 3.2 and 9.0, but in the ISO 29200 "Soil quality--assessment of genotoxic effects on higher plants--V. faba micronucleus test" we recommended to use a control soil with a pH value ranging between 5 and 8 for a more accurate assessment of chemical genotoxicity. We also found that acid pH could increase the genotoxic potential of pollutants, especially heavy metals. With hydrazide maleic spiked soil, plants were placed in a situation of double stress, i.e. toxicity caused by extreme pH values and toxicity induced by the pollutant.

  13. Genotoxic and mutagenic effects of lipid-coated CdSe/ZnS quantum dots.

    PubMed

    Aye, Mélanie; Di Giorgio, Carole; Berque-Bestel, Isabelle; Aime, Ahissan; Pichon, Benoit P; Jammes, Yves; Barthélémy, Philippe; De Méo, Michel

    2013-01-20

    We proposed to evaluate the genotoxicity and mutagenicity of a new quantum dots (QDs) nanoplatform (QDsN), consisting of CdSe/ZnS core-shell QDs encapsulated by a natural fusogenic lipid (1,2-di-oleoyl-sn-glycero-3-phosphocholine (DOPC)) and functionalized by a nucleolipid N-[5'-(2',3'-di-oleoyl) uridine]-N',N',N'-trimethylammoniumtosylate (DOTAU). This QDs nanoplatform may represent a new therapeutic tool for the diagnosis and treatment of human cancers. The genotoxic, mutagenic and clastogenic effects of QDsN were compared to those of cadmium chloride (CdCl(2)). Three assays were used: (1) the Salmonella/microsome assay with four tester strains, (2) the comet assay and (3) the micronucleus test on CHO cells. The contribution of simulated sunlight was studied in the three assays while oxidative events were only explored in the comet assay in aliquots pretreated with the antioxidant l-ergothioneine. We found that QDsN could enter CHO-K1 cells and accumulate in cytoplasmic vesicles. It was not mutagenic in the Salmonella/mutagenicity test whereas CdCl(2) was weakly positive. In the dark, both the QDsN and CdCl(2) similarly induced dose-dependent increases in single-strand breaks and micronuclei. Exposure to simulated sunlight significantly potentiated the genotoxic activities of both QDsN and CdCl(2), but did not significantly increase micronucleus frequencies. l-Ergothioneine significantly reduced but did not completely suppress the DNA-damaging activity of QDsN and CdCl(2). The present results clearly point to the genotoxic properties and the risk of long-term adverse effects of such a nanoplatform if used for human anticancer therapy and diagnosis in the future.

  14. In vitro and in vivo genotoxic effects of somatic cell nuclear transfer cloned cattle meat.

    PubMed

    Lee, Nam-Jin; Yang, Byoung-Chul; Jung, Yu-Ri; Lee, Jung-Won; Im, Gi-Sun; Seong, Hwan-Hoo; Park, Jin-Ki; Kang, Jong-Koo; Hwang, Seongsoo

    2011-09-01

    Although the nutritional composition and health status after consumption of the meat and milk derived from both conventionally bred (normal) and somatic cell nuclear transferred (cloned) animals and their progeny are not different, little is known about their food safeties like genetic toxicity. This study is performed to examine both in vitro (bacterial mutation and chromosome aberration) and in vivo (micronucleus) genotoxicity studies of cloned cattle meat. The concentrations of both normal and cloned cattle meat extracts (0-10×) were tested to five strains of bacteria (Salmonella typhimurium: TA98, TA100, TA1535, and TA1537; Escherichia coli: WP2uvrA) for bacterial mutation and to Chinese hamster lung (CHL/IU) cells for chromosome aberration, respectively. For micronucleus test, ICR mice were divided into five dietary groups: commercial pellets (control), pellets containing 5% (N-5) and 10% (N-10) normal cattle meat, and pellets containing 5% (C-5) and 10% (C-10) cloned cattle meat. No test substance-related genotoxicity was noted in the five bacterial strains, CHL/IU cells, or mouse bone marrow cells, suggesting that the cloned cattle meat potentially may be safe in terms of mutagenic hazards. Thus, it can be postulated that the cloned cattle meat do not induce any harmful genotoxic effects in vitro and in vivo.

  15. Genotoxic Effect in Autoimmune Diseases Evaluated by the Micronucleus Test Assay: Our Experience and Literature Review

    PubMed Central

    Torres-Bugarín, Olivia; Macriz Romero, Nicole; Ramos Ibarra, María Luisa; Flores-García, Aurelio; Valdez Aburto, Penélope; Zavala-Cerna, María Guadalupe

    2015-01-01

    Autoimmune diseases (AD) are classified into organ-specific, systemic, and mixed; all forms of AD share a high risk for cancer development. In AD a destructive immune response induced by autoreactive lymphocytes is started and continues with the production of autoantibodies against different targets; furthermore apoptosis failure and loss of balance in oxidative stress as a consequence of local or systemic inflammation are common features seen in AD as well. Micronucleus (MN) assay can be performed in order to evaluate loss of genetic material in a clear, accurate, fast, simple, and minimally invasive test. The MN formation in the cytoplasm of cells that have undergone proliferation is a consequence of DNA fragmentation during mitosis and the appearance of small additional nuclei during interphase. The MN test, widely accepted for in vitro and in vivo genotoxicity research, provides a sensitive marker of genomic damage associated to diverse conditions. In here, we present a review of our work and other published papers concerning genotoxic effect in AD, identified by means of the MN assay, with the aim of proposing this tool as a possible early biomarker for genotoxic damage, which is a consequence of disease progression. Additionally this biomarker could be used for follow-up, to asses genome damage associated to therapies. PMID:26339592

  16. Neurologic dysfunction and genotoxicity induced by low levels of chlorpyrifos.

    PubMed

    Muller, Mariel; Hess, Leonardo; Tardivo, Agostina; Lajmanovich, Rafael; Attademo, Andres; Poletta, Gisela; Simoniello, Maria Fernanda; Yodice, Agustina; Lavarello, Simona; Chialvo, Dante; Scremin, Oscar

    2014-12-01

    Chlorpyrifos (CPF) is an organophosphorus cholinesterase inhibitor widely used as an insecticide. Neuro and genotoxicity of this agent were evaluated following daily subcutaneous injections at 0.1, 1 and 10mg/kg or its vehicle to laboratory rats during one week, at the end of which somatosensory evoked potentials (SEP) and power spectrum of the electroencephalogram (EEGp) were recorded under urethane anesthesia. In another group of conscious animals, auditory startle reflex (ASR) was evaluated followed, after euthanasia, with measurements of plasma B-esterases, and genotoxicity with the alkaline comet assay (ACA) at the same CPF doses. The results indicated a CPF dose related inhibition of B-esterases. Enhanced inhibition of the ASR by a subthreshold pre-pulse was observed at all doses and ACA showed a significant higher DNA damage than vehicle controls in animals exposed to 10mg/kg CPF. A trend to higher frequencies of EEGp and an increase in amplitude of the first negative wave of the SEP were found at all doses. The first positive wave of the SEP decreased at the CPF dose of 10mg/kg. In summary, a shift to higher EEG frequencies and alterations of somatosensory and auditory input to the central nervous system were sensitive manifestations of CPF toxicity, associated with depression of B-esterases. The changes in electrical activity of the cerebral cortex and DNA damage observed at doses that do not elicit overt toxicity may be useful in the detection of CPF exposure before clinical signs appear.

  17. Genotoxic effects of borax on cultured lymphocytes.

    PubMed

    Pongsavee, Malinee

    2009-03-01

    The effect of borax on human chromosomes was analyzed in this study. Venous blood from 30 male students at Thammasat University, Thailand (age 18-25 years) was collected for lymphocyte cell cultures. This experiment was divided into two groups: the first group was the control group and the second group was the experimental group. The lymphocyte cells in the control group were cultured without borax. The experimental group was divided into four subgroups. The lymphocyte cells in each experimental subgroup were cultured with different concentrations of borax (0.1 mg/ml, 0.15 mg/ml, 0.2 mg/ml and 0.3 mg/ml). Human chromosomes were studied for abnormalities through Giemsa-staining and G-banding. The results show that the numbers of metaphase plates (the metaphase plate which contained 46 chromosomes; 46, XY) and metaphase chromosomes were reduced when lymphocyte cells were cultured with 0.15 mg/ml (57.2%), 0.2 mg/ml (50.8%) and 0.3 mg/ml (42.3%) concentrations of borax. There was a statistically significant difference between the control and experimental subgroups (p < 0.05). Sister chromatid separation was found in the 0.3 mg/ml borax concentration experimental subgroup. This shows that borax (at 0.15, 0.2 and 0.3 mg/ml concentrations) affects the cell and human chromosomes (both numerical and structural abnormalities). Borax may cause human chromosome abnormalities and lead to genetic defects.

  18. Evaluation of genotoxic effects caused by extracts of chlorinated drinking water using a combination of three different bioassays.

    PubMed

    Zeng, Qiang; Zhang, Shao-Hui; Liao, Jing; Miao, Dong-Yue; Wang, Xin-Yi; Yang, Pan; Yun, Luo-Jia; Liu, Ai-Lin; Lu, Wen-Qing

    2015-10-15

    Potential genotoxic effects of chlorinated drinking water now are of a great concern. In this study, raw water, finished water, and tap water from a water plant in Wuhan, China were collected in two different sampling times of the year (January and July). Genotoxic effects of water extracts were evaluated using a combination of three different bioassays: SOS/umu test, HGPRT gene mutation assay, and micronucleus assay, which were separately used to detect DNA damage, gene mutation, and chromosome aberration. The results of three different bioassays showed that all water samples in January and July induced at least one types of genotoxic effects, of which the DNA-damage effects were all detectable. The levels of DNA-damage effects and gene-mutation effects of finished water and tap water in January were higher than those in July. Chlorination could increase the DNA-damage effects of drinking water in January and the gene-mutation effects of drinking water in both January and July, but did not increase the chromosome-aberration effects of drinking water in both January and July. Our results highlighted the importance of using a combination of different bioassays to evaluate the genotoxicity of water samples in different seasons.

  19. DNA methyltransferase I is a mediator of doxorubicin-induced genotoxicity in human cancer cells

    SciTech Connect

    Tan, Hwee Hong; Porter, Alan George

    2009-05-01

    Doxorubicin can induce the formation of extra-nuclear bodies during mitosis termed micronuclei but the underlying causes remain unknown. Here, we show that sub-lethal exposure to doxorubicin-induced micronuclei formation in human cancer cells but not in non-tumorigenic cells. Occurrence of micronuclei coincided with stability of DNMT1 upon doxorubicin assault, and DNMT1 was localized to the micronuclei structures. Furthermore, 5-aza-2'-deoxycytidine-mediated DNMT1 depletion or siDNMT1 knock-down attenuated the frequency of doxorubicin-induced micronucleated cells. Human DNMT1{sup -/-} cells displayed significantly fewer micronuclei compared to DNMT1{sup +/+} cells when challenged with doxorubicin, providing additional evidence for the involvement of DNMT1 in mediating such chromosomal aberrations. Collectively, our results demonstrate a role for DNMT1 in promoting DNA damage-induced genotoxicity in human cancer cells. DNMT1, recently identified as a candidate for doxorubicin-mediated cytotoxicity, is over-expressed in various cancer cell types. We propose that DNMT1 levels in tumor cells may determine the effectiveness of doxorubicin in chemotherapy.

  20. Specific Uptake and Genotoxicity Induced by Polystyrene Nanobeads with Distinct Surface Chemistry on Human Lung Epithelial Cells and Macrophages

    PubMed Central

    Kortulewski, Thierry; Grall, Romain; Gamez, Christelle; Blazy, Kelly; Aguerre-Chariol, Olivier; Chevillard, Sylvie; Braun, Anne; Rat, Patrice; Lacroix, Ghislaine

    2015-01-01

    Nanoparticle surface chemistry is known to play a crucial role in interactions with cells and their related cytotoxic effects. As inhalation is a major route of exposure to nanoparticles, we studied specific uptake and damages of well-characterized fluorescent 50 nm polystyrene (PS) nanobeads harboring different functionalized surfaces (non-functionalized, carboxylated and aminated) on pulmonary epithelial cells and macrophages (Calu-3 and THP-1 cell lines respectively). Cytotoxicity of in mass dye-labeled functionalized PS nanobeads was assessed by xCELLigence system and alamarBlue viability assay. Nanobeads-cells interactions were studied by video-microscopy, flow cytometry and also confocal microscopy. Finally ROS generation was assessed by glutathione depletion dosages and genotoxicity was assessed by γ-H2Ax foci detection, which is considered as the most sensitive technique for studying DNA double strand breaks. The uptake kinetic was different for each cell line. All nanobeads were partly adsorbed and internalized, then released by Calu-3 cells, while THP-1 macrophages quickly incorporated all nanobeads which were located in the cytoplasm rather than in the nuclei. In parallel, the genotoxicity study reported that only aminated nanobeads significantly increased DNA damages in association with a strong depletion of reduced glutathione in both cell lines. We showed that for similar nanoparticle concentrations and sizes, aminated polystyrene nanobeads were more cytotoxic and genotoxic than unmodified and carboxylated ones on both cell lines. Interestingly, aminated polystyrene nanobeads induced similar cytotoxic and genotoxic effects on Calu-3 epithelial cells and THP-1 macrophages, for all levels of intracellular nanoparticles tested. Our results strongly support the primordial role of nanoparticles surface chemistry on cellular uptake and related biological effects. Moreover our data clearly show that nanoparticle internalization and observed adverse effects

  1. Antiproliferative and genotoxic effects of Mikania glomerata (Asteraceae).

    PubMed

    Dalla Nora, Gracieli; Pastori, Tamara; Laughinghouse, Haywood Dail; Do Canto-Dorow, Thais Scotti; Tedesco, Solange Bosio

    2010-12-01

    Mikania glomerata is a plant used in Brazilian traditional medicine, known as 'guaco'. It possesses anti-inflammatory properties and the aqueous extracts of its leaves are indicated for the treatment of diseases of the respiratory tract. This study aimed at evaluating the antiproliferative and genotoxic effect of Mikania glomerata leaf infusions on the cell cycle of onion. The material used was collected in the native environment from Rio Grande do Sul State, Brazil. Aqueous extracts through infusions were prepared in two concentrations: 4g/L (usual concentration) and 16g/L (4x more concentrated) of each of the populations. Two groups of four onion bulbs for each plant population were used plus a control group. The rootlets were fixed in ethanol-acetic acid (3:1), conserved in ethanol 70% and slides were prepared using the squashing technique colored with orcein 2%. The cells were observed and analyzed during cell cycle. Per group of bulbs, 2000 cells were analyzed, and the mean values of the cell number of each of the phases of the cell cycle were calculated, determining the mitotic index (MI). Statistic analyses of the data were carried out by the x2 ( p= 0.05) test. We conclude that M. glomerata presents both antiproliferative and genotoxic activity. PMID:21443139

  2. Nanoceria have no genotoxic effect on human lens epithelial cells

    NASA Astrophysics Data System (ADS)

    Pierscionek, Barbara K.; Li, Yuebin; Yasseen, Akeel A.; Colhoun, Liza M.; Schachar, Ronald A.; Chen, Wei

    2010-01-01

    There are no treatments for reversing or halting cataract, a disease of the structural proteins in the eye lens, that has associations with other age-related degenerative conditions such as Alzheimer's disease. The incidence of cataract and associated conditions is increasing as the average age of the population rises. Protein folding diseases are difficult to assess in vivo as proteins and their age-related changes are assessed after extraction. Nanotechnology can be used to investigate protein changes in the intact lens as well as for a potential means of drug delivery. Nanoparticles, such as cerium oxide (CeO2) which have antioxidant properties, may even be used as a means of treating cataract directly. Prior to use in treatments, nanoparticle genotoxicity must be tested to assess the extent of any DNA or chromosomal damage. Sister chromatid exchanges were measured and DNA damage investigated using the alkaline COMET assay on cultured human lens epithelial cells, exposed to 5 and 10 µg ml-1 of CeO2 nanoparticles (nanoceria). Nanoceria at these dosages did not cause any DNA damage or significant increases in the number of sister chromatid exchanges. The absence of genotoxic effects on lens cells suggests that nanoceria, in the doses and exposures tested in this study, are not deleterious to the eye lens and have the potential for use in studying structural alterations, in developing non-surgical cataract treatments and in investigating other protein folding diseases.

  3. Anti-genotoxic effect of Aloysia triphylla infusion against acrylamide-induced DNA damage as shown by the comet assay technique.

    PubMed

    Zamorano-Ponce, E; Morales, C; Ramos, D; Sepúlveda, C; Cares, S; Rivera, P; Fernández, J; Carballo, M A

    2006-02-28

    Aloysia triphylla a perennial, bushy plant originally from South America has long been used in traditional medicine. Its aqueous extract contains considerable amounts of polyphenolic compounds, namely flavonoids and phenolic acids. In view of the interest in natural phenolic compounds as antioxidant in preventive medicine, this study was undertaken to investigate the chemoprotective effects of cedron leaves infusion against the genetic damage induced by acrylamide (AA) by using the alkaline version of the comet assay technique. Mice were separated in nine groups (eight animals each): (I) untreated, (II) negative control, (III) treated with infusion of cedron leaves 5%, 20 days twice a day, (IV) treated with AA (5 mg/kg b.w.), (V) treated with AA (20 mg/kg b.w.), (VI) treated with AA (30 mg/kg b.w.), (VII) treated with AA (50 mg/kg b.w.), (VIII) pretreated with infusion and treated with AA (50 mg/kg b.w.) and (IX) positive control (cyclophosphamide, 20 mg/kg b.w.). Three hundred blast cells were digitally evaluated per animal from three different slides (100 each). Media of tail moment (TM) values were analyzed by ANOVA test. No statistical differences (p>0.05) were found between untreated animals, negative control and infusion-treated mice. A single dose of AA-induced genetic damage as revealed by a statistically significant increase in TM values (p<0.01). Pretreatment with infusion prior to AA injection significantly reduces the capacity of AA to induce genetic damage. In these conditions, tail moments values did not differ from data obtained in negative control (p>0.05) and exhibit statistical differences from animals treated only with AA (p<0.01). Cell viability was at least 90% in all cases as measured by the trypan blue exclusion method. The ferric reducing ability of plasma (FRAP) method reveals that the plasma of infusion-treated mice has a significantly higher antioxidant capacity than plasma from controls (p<0.01). The results suggest that the infusion

  4. Anti-genotoxic effect of Aloysia triphylla infusion against acrylamide-induced DNA damage as shown by the comet assay technique.

    PubMed

    Zamorano-Ponce, E; Morales, C; Ramos, D; Sepúlveda, C; Cares, S; Rivera, P; Fernández, J; Carballo, M A

    2006-02-28

    Aloysia triphylla a perennial, bushy plant originally from South America has long been used in traditional medicine. Its aqueous extract contains considerable amounts of polyphenolic compounds, namely flavonoids and phenolic acids. In view of the interest in natural phenolic compounds as antioxidant in preventive medicine, this study was undertaken to investigate the chemoprotective effects of cedron leaves infusion against the genetic damage induced by acrylamide (AA) by using the alkaline version of the comet assay technique. Mice were separated in nine groups (eight animals each): (I) untreated, (II) negative control, (III) treated with infusion of cedron leaves 5%, 20 days twice a day, (IV) treated with AA (5 mg/kg b.w.), (V) treated with AA (20 mg/kg b.w.), (VI) treated with AA (30 mg/kg b.w.), (VII) treated with AA (50 mg/kg b.w.), (VIII) pretreated with infusion and treated with AA (50 mg/kg b.w.) and (IX) positive control (cyclophosphamide, 20 mg/kg b.w.). Three hundred blast cells were digitally evaluated per animal from three different slides (100 each). Media of tail moment (TM) values were analyzed by ANOVA test. No statistical differences (p>0.05) were found between untreated animals, negative control and infusion-treated mice. A single dose of AA-induced genetic damage as revealed by a statistically significant increase in TM values (p<0.01). Pretreatment with infusion prior to AA injection significantly reduces the capacity of AA to induce genetic damage. In these conditions, tail moments values did not differ from data obtained in negative control (p>0.05) and exhibit statistical differences from animals treated only with AA (p<0.01). Cell viability was at least 90% in all cases as measured by the trypan blue exclusion method. The ferric reducing ability of plasma (FRAP) method reveals that the plasma of infusion-treated mice has a significantly higher antioxidant capacity than plasma from controls (p<0.01). The results suggest that the infusion

  5. Molecular and structural changes induced by essential oils treatments in Vicia faba roots detected by genotoxicity testing.

    PubMed

    Sturchio, Elena; Boccia, Priscilla; Zanellato, Miriam; Meconi, Claudia; Donnarumma, Lucia; Mercurio, Giuseppe; Mecozzi, Mauro

    2016-01-01

    Over the last few years, there has been an increased interest in exploiting allelopathy in organic agriculture. The aim of this investigation was to examine the effects of essential oil mixtures in order to establish their allelopathic use in agriculture. Two mixtures of essential oils consisting respectively of tea tree oil (TTO) and clove plus rosemary (C + R) oils were tested. Phytotoxicity and genotoxicity tests on the root meristems of Vicia faba minor were performed. A phytotoxic influence was particularly relevant for C + R mixture, while genotoxicity tests revealed significant results with both C + R oil mixture and TTO. Phenotypic analysis on Vicia faba minor primary roots following C + R oil mixture treatment resulted in callose production, an early symptom attributed to lipid peroxidation. The approach described in this study, based on genotoxicity bioassays, might identify specific DNA damage induced by essential oil treatments. These tests may represent a powerful method to evaluate potential adverse effects of different mixtures of essential oils that might be useful in alternative agriculture. Future studies are focusing on the positive synergism of more complex mixtures of essential oils in order to reduce concentrations of potentially toxic components while at the same time maintaining efficacy in antimicrobial and antifungal management.

  6. Molecular and structural changes induced by essential oils treatments in Vicia faba roots detected by genotoxicity testing.

    PubMed

    Sturchio, Elena; Boccia, Priscilla; Zanellato, Miriam; Meconi, Claudia; Donnarumma, Lucia; Mercurio, Giuseppe; Mecozzi, Mauro

    2016-01-01

    Over the last few years, there has been an increased interest in exploiting allelopathy in organic agriculture. The aim of this investigation was to examine the effects of essential oil mixtures in order to establish their allelopathic use in agriculture. Two mixtures of essential oils consisting respectively of tea tree oil (TTO) and clove plus rosemary (C + R) oils were tested. Phytotoxicity and genotoxicity tests on the root meristems of Vicia faba minor were performed. A phytotoxic influence was particularly relevant for C + R mixture, while genotoxicity tests revealed significant results with both C + R oil mixture and TTO. Phenotypic analysis on Vicia faba minor primary roots following C + R oil mixture treatment resulted in callose production, an early symptom attributed to lipid peroxidation. The approach described in this study, based on genotoxicity bioassays, might identify specific DNA damage induced by essential oil treatments. These tests may represent a powerful method to evaluate potential adverse effects of different mixtures of essential oils that might be useful in alternative agriculture. Future studies are focusing on the positive synergism of more complex mixtures of essential oils in order to reduce concentrations of potentially toxic components while at the same time maintaining efficacy in antimicrobial and antifungal management. PMID:26914511

  7. Nitric oxide mitigates arsenic-induced oxidative stress and genotoxicity in Vicia faba L.

    PubMed

    Shukla, Pratiksha; Singh, A K

    2015-09-01

    The protective effects of nitric oxide (NO) against arsenic (As)-induced structural disturbances in Vicia faba have been investigated. As treatment (0.25, 0.50, and 1 mM) resulted in a declined growth of V. faba seedlings. Arsenic treatment stimulates the activity of SOD and CAT while the activities of APX and GST content were decreased. The oxidative stress markers such as superoxide radical, hydrogen peroxide and malondialdehyde (lipid peroxidation) contents were enhanced by As. Overall results revealed that significant accumulation of As suppressed growth, photosynthesis, antioxidant enzymes (SOD, CAT, APX, and GST activity), mitotic index, and induction of different chromosomal abnormalities, hence led to oxidative stress. The concentration of SNP (0.02 mM) was very effective in counteracting the adverse effect of As toxicity. These abnormalities use partially or fully reversed by a simultaneous application of As and NO donor and sodium nitroprusside and has an ameliorating effect against As-induced oxidative stress and genotoxicity in V. faba roots.

  8. Three-Dimensional, Transgenic Cell Models to Quantify Space Genotoxic Effects

    NASA Technical Reports Server (NTRS)

    Gonda, S. R.; Sognier, M. A.; Wu, H.; Pingerelli, P. L.; Glickman, B. W.; Dawson, David L. (Technical Monitor)

    1999-01-01

    The space environment contains radiation and chemical agents known to be mutagenic and carcinogenic to humans. Additionally, microgravity is a complicating factor that may modify or synergize induced genotoxic effects. Most in vitro models fail to use human cells (making risk extrapolation to humans more difficult), overlook the dynamic effect of tissue intercellular interactions on genotoxic damage, and lack the sensitivity required to measure low-dose effects. Currently a need exists for a model test system that simulates cellular interactions present in tissue, and can be used to quantify genotoxic damage induced by low levels of radiation and chemicals, and extrapolate assessed risk to humans. A state-of-the-art, three-dimensional, multicellular tissue equivalent cell culture model will be presented. It consists of mammalian cells genetically engineered to contain multiple copies of defined target genes for genotoxic assessment,. NASA-designed bioreactors were used to coculture mammalian cells into spheroids, The cells used were human mammary epithelial cells (H184135) and Stratagene's (Austin, Texas) Big Blue(TM) Rat 2 lambda fibroblasts. The fibroblasts were genetically engineered to contain -a high-density target gene for mutagenesis (60 copies of lacl/LacZ per cell). Tissue equivalent spheroids were routinely produced by inoculation of 2 to 7 X 10(exp 5) fibroblasts with Cytodex 3 beads (150 micrometers in diameter). at a 20:1 cell:bead ratio, into 50-ml HARV bioreactors (Synthecon, Inc.). Fibroblasts were cultured for 5 days, an equivalent number of epithelial cells added, and the fibroblast/epithelial cell coculture continued for 21 days. Three-dimensional spheroids with diameters ranging from 400 to 600 micrometers were obtained. Histological and immunohistochemical Characterization revealed i) both cell types present in the spheroids, with fibroblasts located primarily in the center, surrounded by epithelial cells; ii) synthesis of extracellular matrix

  9. Genotoxicity in Oreochromis niloticus (Cichlidae) induced by Microcystis spp bloom extract containing microcystins.

    PubMed

    da Silva, R R Pavan; Pires, O R; Grisolia, C K

    2011-09-01

    Studies of genotoxicity in fish caused by cyanobacterial extracts containing microcystins (MCs) can be useful in determining their carcinogenic risk due to a genotoxic mechanism. An extract of cyanobacterial Microcystis ssp, containing MC-LR and -LA from a bloom collected in a eutrophic lake, showed genotoxicity to Oreochromis niloticus. DNA damage (comet assay) was significantly induced in peripheral erythrocytes with both tested concentrations of 6.90 μg kg(-1) bw and 13.80 μg kg(-1) bw through intraperitoneal injection (ip). There was no micronucleus induction after ip injection at concentrations of 6.90 μg kg(-1) bw and 13.80 μg kg(-1) bw. Body exposure resulted in micronucleus induction and DNA damage only at the highest tested concentrations of 103.72 μg L(-1). Thus, comet assay and ip injection revealed the highest levels of the genotoxicity of MCs. Apoptosis-necrosis test carried out at concentrations of 6.90 μg kg(-1) bw and 13.80 μg kg(-1) bw revealed that at low concentrations more apoptosis than necrosis occurred. At higher concentrations more necrosis than apoptosis occurred. PMID:21704053

  10. Exploring the Molecular Mechanisms of Nickel-Induced Genotoxicity and Carcinogenicity: A Literature Review

    PubMed Central

    Cameron, Keyuna S.; Buchner, Virginia; Tchounwou, Paul B.

    2011-01-01

    Nickel, a naturally occurring element that exists in various mineral forms, is mainly found in soil and sediment, and its mobilization is influenced by the physicochemical properties of the soil. Industrial sources of nickel include metallurgical processes such as electroplating, alloy production, stainless steel, and nickel-cadmium batteries. Nickel industries, oil- and coal-burning power plants, and trash incinerators have been implicated in its release into the environment. In humans, nickel toxicity is influenced by the route of exposure, dose, and solubility of the nickel compound. Lung inhalation is the major route of exposure for nickel-induced toxicity. Nickel may also be ingested or absorbed through the skin. The primary target organs are the kidneys and lungs. Other organs such as the liver, spleen, heart and testes may also be affected to a lesser extent. Although the most common health effect is an allergic reaction, research has also demonstrated that nickel is carcinogenic to humans. The focus of the present review is on recent research concerning the molecular mechanisms of nickel-induced genotoxicity and carcinogenicity. We first present a background on the occurrence of nickel in the environment, human exposure, and human health effects. PMID:21905451

  11. Exploring the molecular mechanisms of nickel-induced genotoxicity and carcinogenicity: a literature review.

    PubMed

    Cameron, Keyuna S; Buchner, Virginia; Tchounwou, Paul B

    2011-01-01

    Nickel, a naturally occurring element that exists in various mineral forms, is mainly found in soil and sediment, and its mobilization is influenced by the physicochemical properties of the soil. Industrial sources of nickel include metallurgical processes such as electroplating, alloy production, stainless steel, and nickel-cadmium batteries. Nickel industries, oil- and coal-burning power plants, and trash incinerators have been implicated in its release into the environment. In humans, nickel toxicity is influenced by the route of exposure, dose, and solubility of the nickel compound. Lung inhalation is the major route of exposure for nickel-induced toxicity. Nickel can also be ingested or absorbed through the skin. The primary target organs are the kidneys and lungs. Other organs such as the liver, spleen, heart, and testes can also be affected to a lesser extent. Although the most common health effect is an allergic reaction, research has also demonstrated that nickel is carcinogenic to humans. The focus of the present review is on recent research concerning the molecular mechanisms of nickel-induced genotoxicity and carcinogenicity. We first present a background on the occurrence of nickel in the environment, human exposure, and human health effects. PMID:21905451

  12. Exploring the molecular mechanisms of nickel-induced genotoxicity and carcinogenicity: a literature review.

    PubMed

    Cameron, Keyuna S; Buchner, Virginia; Tchounwou, Paul B

    2011-01-01

    Nickel, a naturally occurring element that exists in various mineral forms, is mainly found in soil and sediment, and its mobilization is influenced by the physicochemical properties of the soil. Industrial sources of nickel include metallurgical processes such as electroplating, alloy production, stainless steel, and nickel-cadmium batteries. Nickel industries, oil- and coal-burning power plants, and trash incinerators have been implicated in its release into the environment. In humans, nickel toxicity is influenced by the route of exposure, dose, and solubility of the nickel compound. Lung inhalation is the major route of exposure for nickel-induced toxicity. Nickel can also be ingested or absorbed through the skin. The primary target organs are the kidneys and lungs. Other organs such as the liver, spleen, heart, and testes can also be affected to a lesser extent. Although the most common health effect is an allergic reaction, research has also demonstrated that nickel is carcinogenic to humans. The focus of the present review is on recent research concerning the molecular mechanisms of nickel-induced genotoxicity and carcinogenicity. We first present a background on the occurrence of nickel in the environment, human exposure, and human health effects.

  13. Genotoxic effects of environmental endocrine disruptors on the aquatic insect Chironomus riparius evaluated using the comet assay.

    PubMed

    Martínez-Paz, Pedro; Morales, Mónica; Martínez-Guitarte, José Luis; Morcillo, Gloria

    2013-12-12

    Genotoxicity is one of the most important toxic endpoints in chemical toxicity testing and environmental risk assessment. The aim of this study was to evaluate the genotoxic potential of various environmental pollutants frequently found in aquatic environments and characterized by their endocrine disrupting activity. Monitoring of DNA damage was undertaken after in vivo exposures of the aquatic larvae of the midge Chironomus riparius, a model organism that represents an abundant and ecologically relevant macroinvertebrate, widely used in freshwater toxicology. DNA-induced damage, resulting in DNA fragmentation, was quantified by the comet assay after short (24 h) and long (96 h) exposures to different concentrations of the selected toxicants: bisphenol A (BPA), nonylphenol (NP), pentachlorophenol (PCP), tributyltin (TBT) and triclosan (TCS). All five compounds were found to have genotoxic activity as demonstrated by significant increases in all the comet parameters (%DNA in tail, tail length, tail moment and Olive tail moment) at all tested concentrations. Persistent exposure did not increase the extent of DNA damage, except for TCS at the highest concentration, but generally there was a reduction in DNA damage thought to be associated with the induction of the detoxification processes and repairing mechanisms. Comparative analysis showed differences in the genotoxic potential between the chemicals, as well as significant time and concentration-dependent variations, which most likely reflect differences in the ability to repair DNA damage under the different treatments. The present report demonstrates the sensitivity of the benthic larvae of C. riparius to these environmental genotoxins suggesting its potential as biomonitor organism in freshwater ecosystems. The results obtained about the DNA-damaging potential of these environmental pollutants reinforce the need for additional studies on the genotoxicity of endocrine active substances that, by linking genotoxic

  14. Enzymatic adaptations to arsenic-induced oxidative stress in Zea mays and genotoxic effect of arsenic in root tips of Vicia faba and Zea mays.

    PubMed

    Duquesnoy, Isabelle; Champeau, Gabrielle Marie; Evray, Germaine; Ledoigt, Gérard; Piquet-Pissaloux, Agnès

    2010-01-01

    Agronomic plant species may display physiological and biochemical responses to oxidative stress caused by heavy metals and metalloids. Zea mays plants were grown hydroponically for eight days at different concentrations of As (0, 134 and 668 μM) and at different pH (4, 7 and 9). Metabolic variations in response to As toxicity were measured using physiological parameters and antioxidant enzymatic activities. A significant decrease in SOD activity was observed in the leaves and roots of Z. mays with the majority of As treatments. As decreased G-POX activity less in leaves than in roots. An increase in the concentration of As increased APX activity in leaves and roots, except As(V) at pH 4 and pH 9 in the leaves and As(III) at pH 9 in the roots, when there was a significant decrease in APX activity at low As concentrations. After exposure to As(V), CAT activity was the same as in the control. As(III) led to an increase in CAT activity in leaves and to a decrease in roots. With increasing concentrations of As(III), CAT activity increased in both leaves and roots whatever the pH. To obtain more detailed knowledge on the effects of arsenate and arsenite exposure on Vicia faba and Z. mays, root meristems were also examined. Roots were fed hydroponically with 134, 334, 534 and 668 μM arsenate or arsenite and 4 × 10(-3)M of maleic hydrazide as positive control, at three different pH. Physiological parameters, the mitotic index and micronuclei frequencies were evaluated in root meristems. At all three pH, the highest As(V) and As(III) concentrations induced a substantial modification in root colour, increased root thickness with stiffening, and reduced root length. High concentrations also caused a significant decrease in the mitotic index, and micronucleus chromosomic aberrations were observed in the root meristems of both species.

  15. Promising anticancer activity of a lichen, Parmelia sulcata Taylor, against breast cancer cell lines and genotoxic effect on human lymphocytes.

    PubMed

    Ari, Ferda; Ulukaya, Engin; Oran, Seyhan; Celikler, Serap; Ozturk, Sule; Ozel, Mustafa Zafer

    2015-05-01

    Plants are still to be explored for new anti-cancer compounds because overall success in cancer treatment is still not satisfactory. As a new possible source for such compounds, the lichens are recently taking a great attention. We, therefore, explored both the genotoxic and anti-growth properties of lichen species Parmelia sulcata Taylor. The chemical composition of P. sulcata was analyzed with comprehensive gas chromatography-time of flight mass spectrometry. Anti-growth effect was tested in human breast cancer cell lines (MCF-7 and MDA-MB-231) by the MTT and ATP viability assays, while the genotoxic activity was studied by assays for micronucleus, chromosomal aberration and DNA fragmentation in human lymphocytes culture. Cell death modes (apoptosis/necrosis) were morphologically assessed. P. sulcata inhibited the growth in a dose-dependent manner up to a dose of 100 μg/ml and induced caspase-independent apoptosis. It also showed genotoxic activity at doses (>125 μg/ml) higher than that required for apoptosis. These results suggest that P. sulcata may induce caspase-independent apoptotic cell death at lower doses, while it may be genotoxic at relatively higher doses. PMID:24676908

  16. Iron induced genotoxicity: attenuation by vitamin C and its optimization

    PubMed Central

    Parveen, Nuzhat; Ahmad, Shoeb

    2014-01-01

    Vitamin C (VC) is a well-known antioxidant and strong free radical scavenger. Its antioxidant activity is useful for protection of cellular macromolecules, particularly DNA, from oxidative damage induced by different agents. This study was undertaken to evaluate the optimum level of VC in attenuating the chromosome aberrations (CAs) and DNA damage after iron sulfate (FeSO4) acute administration in Wistar rats. The results exhibited that the increase of CAs and DNA damage induced by FeSO4, 200 mg Fe/kg, could be reduced significantly by VC pretreatment at the dose of 500 mg/kg (p<0.001), but not in the 100 mg/kg group. The findings provide evidence that VC at the dose of 500 mg/kg exerted a possible protective effect against FeSO4 induced CAs and DNA damage. The possible mechanisms of VC may be attributed to its property as a free radical scavenger or to its indirect action in reducing the level of reactive oxygen species (ROS). PMID:26109893

  17. In Vitro Analysis of Early Genotoxic and Cytotoxic Effects of Okadaic Acid in Different Cell Types of the Mussel Mytilus galloprovincialis.

    PubMed

    Prego-Faraldo, María Verónica; Valdiglesias, Vanessa; Laffon, Blanca; Eirín-López, José M; Méndez, Josefina

    2015-01-01

    Okadaic acid (OA) is the predominant biotoxin responsible for diarrhetic shellfish poisoning (DSP) syndrome in humans. While its harmful effects have been extensively studied in mammalian cell lines, the impact on marine organisms routinely exposed to OA is still not fully known. Few investigations available on bivalve molluscs suggest less genotoxic and cytotoxic effects of OA at high concentrations during long exposure times. In contrast, no apparent information is available on how sublethal concentrations of OA affect these organisms over short exposure times. In order to fill this gap, this study addressed for the first time in vitro analysis of early genotoxic and cytotoxic effects attributed to OA in two cell types of the mussel Mytilus galloprovincialis. Accordingly, hemocytes and gill cells were exposed to low OA concentrations (10, 50, 100, 200, or 500 nM) for short periods of time (1 or 2 h). The resulting DNA damage, as apoptosis and necrosis, was subsequently quantified using the comet assay and flow cytometry, respectively. Data demonstrated that (1) mussel hemocytes seem to display a resistance mechanism against early genotoxic and cytotoxic OA-induced effects, (2) mussel gill cells display higher sensitivity to early OA-mediated genotoxicity than hemocytes, and (3) mussel gill cells constitute more suitable systems to evaluate the genotoxic effect of low OA concentrations in short exposure studies. Taken together, this investigation provides evidence supporting the more reliable suitability of mussel gill cells compared to hemocytes to evaluate the genotoxic effect of low short-duration exposure to OA.

  18. 4-Aminoantipyrine reduces toxic and genotoxic effects of doxorubicin, cisplatin, and cyclophosphamide in male mice.

    PubMed

    Berno, Claudia Rodrigues; Rós, Barbara de Toledo; da Silveira, Ingridhy Ostaciana Maia Freitas; Coelho, Henrique Rodrigues; Antoniolli, Andréia Conceição Milan Brochado; Beatriz, Adilson; de Lima, Dênis Pires; Monreal, Antônio Carlos Duenhas; Sousa, Fabricio Garmus; da Silva Gomes, Roberto; Oliveira, Rodrigo Juliano

    2016-07-01

    The analgesic drug dipyrone is used to treat side effects (including pain and fever) of cancer chemotherapeutic agents. Dipyrone is metabolized to 4-aminoantipyrine (4-AA), a PGE2-dependent blocker and inhibitor of cyclooxygenase (COX). We evaluated the genotoxic, mutagenic, apoptotic, and immunomodulatory activities of 4-AA in vivo and the effects of its combination with the antineoplastic drugs doxorubicin, cisplatin, and cyclophosphamide. 4-AA did not cause genotoxic/mutagenic damage, splenic phagocytosis, or leukocyte alterations. However, when combined with the antineoplastic agents, 4-AA decreased their genotoxic, mutagenic, apoptotic, and phagocytic effects. These results suggest that 4-AA might interfere with DNA damage-mediated chemotherapy. PMID:27402479

  19. Proteomic analysis of beryllium-induced genotoxicity in an Escherichia coli mutant model system.

    PubMed

    Taylor-McCabe, Kirsten J; Wang, Zaolin; Sauer, Nancy N; Marrone, Babetta L

    2006-03-01

    Beryllium is the second lightest metal, has a high melting point and high strength-to-weight ratio, and is chemically stable. These unique chemical characteristics make beryllium metal an ideal choice as a component material for a wide variety of applications in aerospace, defense, nuclear weapons, and industry. However, inhalation of beryllium dust or fumes induces significant health effects, including chronic beryllium disease and lung cancer. In this study, the mutagenicity of beryllium sulfate (BeSO(4)) and the comutagenicity of beryllium with a known mutagen 1-methyl-3-nitro-1-nitrosoguanidine (MNNG) were evaluated using a forward mutant detection system developed in Escherichia coli. In this system, BeSO(4) was shown to be weakly mutagenic alone and significantly enhanced the mutagenicity of MNNG up to 3.5-fold over MNNG alone. Based on these results a proteomic study was conducted to identify the proteins regulated by BeSO(4). Using the techniques of 2-DE and oMALDI-TOF MS, we successfully identified 32 proteins being differentially regulated by beryllium and/or MNNG in the E. coli test system. This is the first study to describe the proteins regulated by beryllium in vitro, and the results suggest several potential pathways for the focus of further research into the mechanisms underlying beryllium-induced genotoxicity. PMID:16447159

  20. Arsenic-induced genotoxicity in Nile tilapia (Orechromis niloticus); the role of Spirulina platensis extract.

    PubMed

    Sayed, Alaa El-Din H; Elbaghdady, Heba Allah M; Zahran, Eman

    2015-12-01

    Arsenic (As) is one of the most relevant environmental global single substance toxicants that have long been regarded as a carcinogenic and genotoxic potential. In this respect, we evaluated the cytogenetic effect of arsenic exposure in Nile tilapia (Oreochromis niloticus), in terms of erythrocyte alteration, apoptosis, and induction of micronuclei. Spirulina platensis (SP) is a filamentous cyanobacterium microalgae with potent dietary phytoantioxidant, anti-inflammatory, and anti-cancerous properties supplementation. The protective role of Spirulina as supplementary feeds was studied in Nile tilapia (O. niloticus) against arsenic-induced cytogenotoxicity. Four groups were assigned as control group (no SP or As), As group (exposed to water-born As in the form of NaAsO2 at 7 ppm), SP1 (SP at 7.5% + As at the same level of exposure), and SP2 (SP at 10% + As at the same level of exposure). As-treated group had a significant increase in all cytogenetic analyses including erythrocyte alteration, apoptosis, and induction of micronuclei after 2 weeks with continuous increase in response after 3 weeks. The combined treatment of Spirulina at two different concentrations of 7.5 and 10% had significantly declined the induction of erythrocyte alteration, apoptosis, and micronuclei formation induced by arsenic intoxication. PMID:26573688

  1. Arsenic-induced genotoxicity in Nile tilapia (Orechromis niloticus); the role of Spirulina platensis extract.

    PubMed

    Sayed, Alaa El-Din H; Elbaghdady, Heba Allah M; Zahran, Eman

    2015-12-01

    Arsenic (As) is one of the most relevant environmental global single substance toxicants that have long been regarded as a carcinogenic and genotoxic potential. In this respect, we evaluated the cytogenetic effect of arsenic exposure in Nile tilapia (Oreochromis niloticus), in terms of erythrocyte alteration, apoptosis, and induction of micronuclei. Spirulina platensis (SP) is a filamentous cyanobacterium microalgae with potent dietary phytoantioxidant, anti-inflammatory, and anti-cancerous properties supplementation. The protective role of Spirulina as supplementary feeds was studied in Nile tilapia (O. niloticus) against arsenic-induced cytogenotoxicity. Four groups were assigned as control group (no SP or As), As group (exposed to water-born As in the form of NaAsO2 at 7 ppm), SP1 (SP at 7.5% + As at the same level of exposure), and SP2 (SP at 10% + As at the same level of exposure). As-treated group had a significant increase in all cytogenetic analyses including erythrocyte alteration, apoptosis, and induction of micronuclei after 2 weeks with continuous increase in response after 3 weeks. The combined treatment of Spirulina at two different concentrations of 7.5 and 10% had significantly declined the induction of erythrocyte alteration, apoptosis, and micronuclei formation induced by arsenic intoxication.

  2. Deltamethrin-induced genotoxicity and testicular injury in rats: comparison with biopesticide.

    PubMed

    Ismail, Manal F; Mohamed, Hanaa M

    2012-10-01

    Deltamethrin is a synthetic pyrethroid insecticide used extensively in pest control. Aim of the current study was to investigate the ability of deltamethrin-based commercial formulation to induce genotoxicity and testicular injury in rats in comparison to the use of the biopesticide; Bacillus thuringiensis. Rats were divided into three groups: Group I (DEL) received deltamethrin, 5 mg/kgb.w./day orally, in corn oil. Group II (Biopesticide, B. thuringiensis) received oral suspension of the biopesticide at daily dose of 8400 mg/kgb.w./day. Group III (Control) received appropriate volume of corn oil. After 4 weeks, deltamethrin-treated rats showed decreased serum testosterone, luteinizing and follicle-stimulating hormone levels. Testicular total oxidant capacity (TOC), poly (ADP-ribose) polymerase (PARP), lactate dehydrogenase (LDH) and DNA damage were significantly increased. Significant increase in bone marrow chromosomal aberrations, induced by deltamethrin, including chromatid breaks, deletions, fragments and gaps was also observed. RT-PCR demonstrated significant up-regulation in testicular mRNA for glutathione-s-transferase and heat-shock protein-70 (HSP-70) whereas steroidogenic acute regulatory (StAR) mRNA was down-regulated after deltamethrin exposure. Oral administration of the biopesticide, under the condition of our study, was found to be safe when compared to the deleterious effect of deltamethrin in rats. PMID:22889898

  3. Enhanced cytotoxic and genotoxic effects of gadolinium following ELF-EMF irradiation in human lymphocytes.

    PubMed

    Cho, Seunghyun; Lee, Younghyun; Lee, Sunyeong; Choi, Young Joo; Chung, Hai Won

    2014-10-01

    There are many studies of Gd nephrotoxicity and neurotoxicity, whereas research on cyto- and genotoxicity in normal human lymphocytes is scarce. It is important to investigate the effect of extremely low-frequency electromagnetic fields (ELF-EMF) on Gd toxicity, as patients are co-exposed to Gd and ELF-EMF generated by MRI scanners. We investigated the cytotoxicity and genotoixcity of Gd and the possible enhancing effect of ELF-EMF on Gd toxicity in cultured human lymphocytes by performing a micronuclei (MN) assay, trypan blue dye exclusion, single cell gel electrophoresis, and apoptosis analyses using flow cytometry. Isolated lymphocytes were exposed to 0.2-1.2 mM of Gd only or in combination with a 60-Hz ELF-EMF of 0.8-mT field strength. Exposing human lymphocytes to Gd resulted in a concentration- and time-dependent decrease in cell viability and an increase in MN frequency, single strand DNA breakage, apoptotic cell death, and ROS production. ELF-EMF (0.8 mT) exposure also increased cell death, MN frequency, olive tail moment, and apoptosis induced by Gd treatment alone. These results suggest that Gd induces DNA damage and apoptotic cell death in human lymphocytes and that ELF-EMF enhances the cytotoxicity and genotoxicity of Gd. PMID:24479558

  4. Zinc oxide nanoparticle induced genotoxicity in primary human epidermal keratinocytes.

    PubMed

    Sharma, Vyom; Singh, Suman K; Anderson, Diana; Tobin, Desmond J; Dhawan, Alok

    2011-05-01

    Zinc oxide (ZnO) nanoparticles are widely used in cosmetics and sunscreens. Human epidermal keratinocytes may serve as the first portal of entry for these nanoparticles either directly through topically applied cosmetics or indirectly through any breaches in the skin integrity. Therefore, the objective of the present study was to assess the biological interactions of ZnO nanoparticles in primary human epidermal keratinocytes (HEK) as they are the most abundant cell type in the human epidermis. Cellular uptake of nanoparticles was investigated by scanning electron microscopy using back scattered electrons imaging as well as transmission electron microscopy. The electron microscopy revealed the internalization of ZnO nanoparticles in primary HEK after 6 h exposure at 14 microg/ml concentration. ZnO nanoparticles exhibited a time (6-24 h) as well as concentration (8-20 microg/ml) dependent inhibition of mitochondrial activity as evident by the MTT assay. A significant (p < 0.05) induction in DNA damage was observed in cells exposed to ZnO nanoparticles for 6 h at 8 and 14 microg/ml concentrations compared to control as evident in the Comet assay. This is the first study providing information on biological interactions of ZnO nanoparticles with primary human epidermal keratinocytes. Our findings demonstrate that ZnO nanoparticles are internalized by the human epidermal keratinocytes and elicit a cytotoxic and genotoxic response. Therefore, caution should be taken while using consumer products containing nanoparticles as any perturbation in the skin barrier could expose the underlying cells to nanoparticles.

  5. Genotoxicity induced by Roundup® (Glyphosate) in tegu lizard (Salvator merianae) embryos.

    PubMed

    Schaumburg, Laura G; Siroski, Pablo A; Poletta, Gisela L; Mudry, Marta D

    2016-06-01

    Environmental contaminants produce multiple adverse consequences at individual, population and ecosystem levels. High volumes of agrochemicals applied to great variety of crops, together with agricultural expansion, generate great concerns due to the impact for the environment and large risk implicated for wildlife. The lack of data on these threats is striking. The tegu lizard (Salvator merianae) is one of the species that live in environments under contaminant effects. Several characteristics allow proposing this species as a potential sentinel organism for the monitoring of pesticides in their habitat. The present study is the first report about genotoxicity in tegu lizard neonates after embryonic exposure to Roundup® (glyphosate 66.2%). The micronucleus test (MN), nuclear abnormalities (NAs) assay and comet assay (CA) were used as biomarkers of genotoxic effects induced in erythrocytes by topical exposure of the eggs to the glyphosate commercial formulation Roundup® (RU), in laboratory controlled conditions. A total of 96 eggs were distributed in six groups exposed to RU (50, 100, 200, 400, 800, 1600μg/egg), one positive control (PC; 200μg cyclophosphamide/egg) and one negative control (NC; distilled water). No teratogenic effects were observed in any of the exposed or control neonates. A significant increase in DNA damage was observed in all concentrations higher than 100μg/egg with respect to NC (p<0.05). However, no statistical differences were found in the frequencies of MN and NAs in any group exposed to RU compared to the NC. No statistically significant differences were found in the size of the lizards at birth or after six months post-exposure (p>0.05). Our results provide new information about the undesirable effects of the glyphosate-based herbicide formulations RU on this lizard species that inhabits areas permanently exposed to several pesticide formulations. We consider of utmost necessity a strict regulation of the agrochemical application

  6. Genotoxicity induced by Roundup® (Glyphosate) in tegu lizard (Salvator merianae) embryos.

    PubMed

    Schaumburg, Laura G; Siroski, Pablo A; Poletta, Gisela L; Mudry, Marta D

    2016-06-01

    Environmental contaminants produce multiple adverse consequences at individual, population and ecosystem levels. High volumes of agrochemicals applied to great variety of crops, together with agricultural expansion, generate great concerns due to the impact for the environment and large risk implicated for wildlife. The lack of data on these threats is striking. The tegu lizard (Salvator merianae) is one of the species that live in environments under contaminant effects. Several characteristics allow proposing this species as a potential sentinel organism for the monitoring of pesticides in their habitat. The present study is the first report about genotoxicity in tegu lizard neonates after embryonic exposure to Roundup® (glyphosate 66.2%). The micronucleus test (MN), nuclear abnormalities (NAs) assay and comet assay (CA) were used as biomarkers of genotoxic effects induced in erythrocytes by topical exposure of the eggs to the glyphosate commercial formulation Roundup® (RU), in laboratory controlled conditions. A total of 96 eggs were distributed in six groups exposed to RU (50, 100, 200, 400, 800, 1600μg/egg), one positive control (PC; 200μg cyclophosphamide/egg) and one negative control (NC; distilled water). No teratogenic effects were observed in any of the exposed or control neonates. A significant increase in DNA damage was observed in all concentrations higher than 100μg/egg with respect to NC (p<0.05). However, no statistical differences were found in the frequencies of MN and NAs in any group exposed to RU compared to the NC. No statistically significant differences were found in the size of the lizards at birth or after six months post-exposure (p>0.05). Our results provide new information about the undesirable effects of the glyphosate-based herbicide formulations RU on this lizard species that inhabits areas permanently exposed to several pesticide formulations. We consider of utmost necessity a strict regulation of the agrochemical application

  7. Comparative efficacy of two microdoses of a potentized homoeopathic drug, Cadmium Sulphoricum, in reducing genotoxic effects produced by cadmium chloride in mice: a time course study

    PubMed Central

    Datta, Swapna S; Mallick, Palash P; Rahman Khuda-Bukhsh, Anisur AR

    2001-01-01

    Background Cadmium poisoning in the environment has assumed an alarming problem in recent years. Effective antimutagenic agents which can reverse or combat cadmium induced genotoxicity in mice have not yet been reported. Therefore, in the present study, following the homeopathic principle of "like cures like", we tested the efficacy of two potencies of a homeopathic drug, Cadmium Sulphoricum (Cad Sulph), in reducing the genotoxic effects of Cadmium chloride in mice. Another objective was to determine the relative efficacy of three administrative modes, i.e. pre-, post- and combined pre and post-feeding of the homeopathic drugs. For this, healthy mice, Mus musculus, were intraperitoneally injected with 0.008% solution of CdCl2 @ 1 ml/100 gm of body wt (i.e. 0.8 mcg/gm of bw), and assessed for the genotoxic effects through such studies as chromosome aberrations (CA), micronucleated erythrocytes (MNE), mitotic index (MI) and sperm head anomaly (SHA), keeping suitable succussed alcohol fed (positive) and CdCl2 untreated normal (negative) controls. The CdCl2 treated mice were divided into 3 subgroups, which were orally administered with the drug prior to, after and both prior to and after injection of CdCl2 at specific fixation intervals and their genotoxic effects were analyzed. Results While the CA, MNE and SHA were reduced in the drug fed series as compared to their respective controls, the MI showed an apparent increase. The combined pre- and post-feeding of Cad Sulph showed maximum reduction of the genotoxic effects. Conclusions Both Cad Sulph-30 and 200 were able to combat cadmium induced genotoxic effects in mice and that combined pre- and post-feeding mode of administration was found to be most effective in reducing the genotoxic effect of CdCl2 followed by the post-feeding mode. PMID:11737881

  8. Effects of single and multi walled carbon nanotubes on macrophages: cyto and genotoxicity and electron microscopy.

    PubMed

    Di Giorgio, Maria Laura; Di Bucchianico, Sebastiano; Ragnelli, Anna Maria; Aimola, Pierpaolo; Santucci, Sandro; Poma, Anna

    2011-05-18

    Production of nanotechnology-based materials is increasing worldwide: it is essential to evaluate their potential toxicity. Among these nanomaterials, carbon nanotubes (CNTs) have tremendous potential in many areas of research and applications. We have investigated the cyto- and genotoxic effects of single and multi-walled CNTs (SWCNTs, MWCNTs) and carbon black (CB) on the mouse macrophage cell line RAW 264.7. Specifically we have investigated inflammatory response, release of tumor necrosis factor-α (TNF-α), intracellular reactive oxygen species (ROS) production, cell death (both necrosis and apoptosis), chromosomal aberrations and cellular ultrastructural alteration caused by CB, MWCNTs and SWCNTs. Our data confirm that both CNTs and CB are cyto and geno-toxic to RAW 264.7 mouse macrophages. CNTs exposure induced ROS release, necrosis and chromosomal aberrations but did not cause an inflammatory response. In addition CNTs induce ultrastructural damage and apoptosis. CNTs penetrate the cell membrane and individual MWCNTs are seen associated with the nuclear envelope.

  9. Cytotoxic, Genotoxic, and Neurotoxic Effects of Mg, Pb, and Fe on Pheochromocytoma (PC-12) Cells

    PubMed Central

    Sanders, Talia; Liu, Yi-Ming; Tchounwou, Paul B.

    2014-01-01

    Metals such as lead (Pb), magnesium (Mg), and iron (Fe) are ubiquitous in the environment as a result of natural occurrence and anthropogenic activities. Although Mg, Fe and others are considered essential elements, high level of exposure has been associated with severe adverse health effects including cardiovascular, hematological, nephrotoxic, hepatotoxic, and neurologic abnormalities in humans. In the present study we hypothesized that Mg, Pb, and Fe are cytotoxic, genotoxic and neurotoxic, and their toxicity is mediated through oxidative stress and alteration in protein expression. To test the hypothesis, we used the pheochromocytoma (PC-12) cell line as a neuro cell model and performed the LDH assay for cell viability, Comet assay for DNA damage, Western blot for oxidative stress, and HPLC-MS to assess the concentration levels of neurological biomarkers such as glutamate, dopamine (DA), and 3-methoxytyramine (3-MT). The results of this study clearly show that Mg, Pb, and Fe, respectively in the form of MgSO4, Pb(NO3)2, FeCl2, and FeCl3 induce cytotoxicity, oxidative stress, and genotoxicity in PC-12 cells. In addition, exposure to these metallic compounds caused significant changes in the concentration levels of glutamate, dopamine, and 3-MT in PC-12 cells. Taken together the findings suggest that MgSO4, Pb(NO3)2, FeCl2, and FeCl3 have the potential to induce substantial toxicity to PC-12 cells. PMID:24942330

  10. Oxidative stress and genotoxic effect of zinc oxide nanoparticles in freshwater snail Lymnaea luteola L.

    PubMed

    Ali, Daoud; Alarifi, Saud; Kumar, Sudhir; Ahamed, Maqusood; Siddiqui, Maqsood A

    2012-11-15

    Understanding the toxic effects of nanoparticles on aquatic organism is the biggest obstacle to the safe development of nanotechnology. However, little is known about the toxic mechanisms of zinc oxide nanoparticles (ZnONPs) in freshwater snail Lymnaea luteola (L. luteola). This study was designed to investigate the possible mechanisms of genotoxicity induced by ZnONPs in freshwater snail L. luteola. ZnONPs (32 μg/ml) elicited a significant (p<0.01) reduction in glutathione (42.10% and 61.40%), glutathione-S-transferase (25.60% and 40.24%) and glutathione peroxidase (21.73% and 39.13%) with a concomitant increase in malondialdehyde level (54.50% and 57.14%; p<0.01) and catalase (34.88% and 52.56%; p<0.01) in digestive gland of L. luteola after 24 and 96 h exposure, respectively. However, a statistically significant (p<0.01) induction in DNA damage was observed by the comet assay in digestive gland cells treated with ZnONPs for 24 and 96 h. Thus, the results demonstrate that ZnONPs induce genotoxicity in digestive gland cells through oxidative stress. Freshwater snail L. luteola may be used as suitable test model for nanoecotoxicological studies in future.

  11. Beryllium metal I. experimental results on acute oral toxicity, local skin and eye effects, and genotoxicity.

    PubMed

    Strupp, Christian

    2011-01-01

    The toxicity of soluble metal compounds is often different from that of the parent metal. Since no reliable data on acute toxicity, local effects, and mutagenicity of beryllium metal have ever been generated, beryllium metal powder was tested according to the respective Organisation for Economical Co-Operation and Development (OECD) guidelines. Acute oral toxicity of beryllium metal was investigated in rats and local effects on skin and eye in rabbits. Skin-sensitizing properties were investigated in guinea pigs (maximization method). Basic knowledge about systemic bioavailability is important for the design of genotoxicity tests on poorly soluble substances. Therefore, it was necessary to experimentally compare the capacities of beryllium chloride and beryllium metal to form ions under simulated human lung conditions. Solubility of beryllium metal in artificial lung fluid was low, while solubility in artificial lysosomal fluid was moderate. Beryllium chloride dissolution kinetics were largely different, and thus, metal extracts were used in the in vitro genotoxicity tests. Genotoxicity was investigated in vitro in a bacterial reverse mutagenicity assay, a mammalian cell gene mutation assay, a mammalian cell chromosome aberration assay, and an unscheduled DNA synthesis (UDS) assay. In addition, cell transformation was tested in a Syrian hamster embryo cell assay, and potential inhibition of DNA repair was tested by modification of the UDS assay. Beryllium metal was found not to be mutagenic or clastogenic based on the experimental in vitro results. Furthermore, treatment with beryllium metal extracts did not induce DNA repair synthesis, indicative of no DNA-damaging potential of beryllium metal. A cell-transforming potential and a tendency to inhibit DNA repair when the cell is severely damaged by an external stimulus were observed. Beryllium metal was also found not to be a skin or eye irritant, not to be a skin sensitizer, and not to have relevant acute oral

  12. Beryllium Metal I. Experimental Results on Acute Oral Toxicity, Local Skin and Eye Effects, and Genotoxicity

    PubMed Central

    Strupp, Christian

    2011-01-01

    The toxicity of soluble metal compounds is often different from that of the parent metal. Since no reliable data on acute toxicity, local effects, and mutagenicity of beryllium metal have ever been generated, beryllium metal powder was tested according to the respective Organisation for Economical Co-Operation and Development (OECD) guidelines. Acute oral toxicity of beryllium metal was investigated in rats and local effects on skin and eye in rabbits. Skin-sensitizing properties were investigated in guinea pigs (maximization method). Basic knowledge about systemic bioavailability is important for the design of genotoxicity tests on poorly soluble substances. Therefore, it was necessary to experimentally compare the capacities of beryllium chloride and beryllium metal to form ions under simulated human lung conditions. Solubility of beryllium metal in artificial lung fluid was low, while solubility in artificial lysosomal fluid was moderate. Beryllium chloride dissolution kinetics were largely different, and thus, metal extracts were used in the in vitro genotoxicity tests. Genotoxicity was investigated in vitro in a bacterial reverse mutagenicity assay, a mammalian cell gene mutation assay, a mammalian cell chromosome aberration assay, and an unscheduled DNA synthesis (UDS) assay. In addition, cell transformation was tested in a Syrian hamster embryo cell assay, and potential inhibition of DNA repair was tested by modification of the UDS assay. Beryllium metal was found not to be mutagenic or clastogenic based on the experimental in vitro results. Furthermore, treatment with beryllium metal extracts did not induce DNA repair synthesis, indicative of no DNA-damaging potential of beryllium metal. A cell-transforming potential and a tendency to inhibit DNA repair when the cell is severely damaged by an external stimulus were observed. Beryllium metal was also found not to be a skin or eye irritant, not to be a skin sensitizer, and not to have relevant acute oral

  13. Cyto/Genotoxic Effects of Pistacia atlantica Resin, a Traditional Gum.

    PubMed

    Rahbar Saadat, Yalda; Barzegari, Abolfazl; Zununi Vahed, Sepideh; Saeedi, Nazli; Eskandani, Morteza; Omidi, Yadollah; Barar, Jaleh

    2016-06-01

    In recent years, many researchers have focused on native plants to search for a new source of natural components with medical approach, especially by means of anticancer potential. One of these natural components is Saqez, the resin of Pistacia atlantica sub-kurdica with the local name of Baneh. It has been reported as an anticancer and apoptosis inducer component; therefore, in this research, we aimed to evaluate the solvated resin's possible cyto/genotoxic effects. The cell viability was assessed using MTT assay. Flow cytometry analysis was performed to distinguish the role of apoptosis and necrosis in cell toxicity, which was further confirmed by Comet and DNA ladder assay, and 4,6-diamidino2-phenylindole (DAPI) staining. Pistacia atlantica's resin decreased the growth of the treated cells in a dose- and time-dependent manner, and single-strand DNA breaks have been observed through comet assay. Moreover, morphological changes of DAPI-stained cells showed fragmentation in the nucleus of resin-treated cells. In addition, early and late apoptosis in the treated cells was determined by flow cytometry analysis, also DNA ladder assay showed fragmentation in DNA of the treated cells. This study has revealed that the resin has significant cyto/genotoxic effects on cancerous and noncancerous cell lines. Our results show that apoptosis and necrosis are the dominant mechanisms by which the resin affects cell lines. Although the resin of P. atlantica is the main source of mastic gum and has been used for a long time as a natural remedy for different diseases, it is necessary to perform thorough analysis due to its cyto/genotoxicity in vivo. PMID:27196631

  14. Genotoxic and clastogenic effects of monohaloacetic acid drinking water disinfection by-products in primary human lymphocytes.

    PubMed

    Escobar-Hoyos, Luisa F; Hoyos-Giraldo, Luz Stella; Londoño-Velasco, Elizabeth; Reyes-Carvajal, Ingrid; Saavedra-Trujillo, Diana; Carvajal-Varona, Silvio; Sánchez-Gómez, Adalberto; Wagner, Elizabeth D; Plewa, Michael J

    2013-06-15

    The haloacetic acids (HAAs) are the second-most prevalent class of drinking water disinfection by-products formed by chemical disinfectants. Previous studies have determined DNA damage and repair of HAA-induced lesions in mammalian and human cell lines; however, little is known of the genomic DNA and chromosome damage induced by these compounds in primary human cells. The aim of this study was to evaluate the genotoxic and clastogenic effects of the monoHAA disinfection by-products in primary human lymphocytes. All monoHAAs were genotoxic in primary human lymphocytes, the rank order of genotoxicity and cytotoxicity was IAA > BAA > CAA. After 6 h of repair time, only 50% of the DNA damage (maximum decrease in DNA damage) was repaired compared to the control. This demonstrates that primary human lymphocytes are less efficient in repairing the induced damage by monoHAAs than previous studies with mammalian cell lines. In addition, the monoHAAs induced an increase in the chromosome aberration frequency as a measurement of the clastogenic effect of these compounds. These results coupled with genomic technologies in primary human cells and other mammalian non-cancerous cell lines may lead to the identification of biomarkers that may be employed in feedback loops to aid water chemists and engineers in the overall goal of producing safer drinking water.

  15. Single and combined genotoxic and cytotoxic effects of two xenobiotics widely used in intensive aquaculture.

    PubMed

    Jerbi, Mohamed Ali; Ouanes, Zouhour; Besbes, Raouf; Achour, Lotfi; Kacem, Adnen

    2011-09-18

    Several chemicals are used in aquaculture to prevent or to treat disease outbreaks. These substances are mainly administered by two different routes: by prolonged immersion or by mixing into the diet. In the case of intensive aquaculture, the chemicals that are most frequently applied by immersion are formaldehyde (FA) 37% and oxytetracycline (OTC). The first is highly effective against most protozoa, as well as some of the most common parasites such as monogenetic trematodes. OTC presents a large spectrum of antibacterial activities and is used to treat systemic bacterial infections that affect fish. Under therapeutic use, FA (37%) is applied prophylactically at 200ml/m(3), whereas OTC is used curatively at 40g/m(3). The goal of the present study is to assess genotoxic and cytotoxic effects associated with exposure of the European sea bass (Dicentrarchus labrax) to FA37% and OTC under the same conditions as those applied in intensive aquaculture systems. To this end the micronucleus (MN) assay was applied in erythrocytes. Our results show that both tested chemicals present genotoxic and cytotoxic potential following a time-dependent pattern. Remarkably, the combined treatment induces a cumulative effect, which is particularly pronounced after 15 days of exposure. This suggests the critical hazards associated with exposure to FA and OTC when applied or released together.

  16. Protective in vivo effect of curcumin on copper genotoxicity evaluated by comet and micronucleus assays.

    PubMed

    Corona-Rivera, Alfredo; Urbina-Cano, Patricia; Bobadilla-Morales, Lucina; Vargas-Lares, José de Jesus; Ramirez-Herrera, Mario Alberto; Mendoza-Magaua, Maria Luisa; Troyo-Sanroman, Rogelio; Diaz-Esquivel, Pedro; Corona-Rivera, Jorge Roman

    2007-01-01

    Curcumin is a phytochemical with antiinflammatory, antioxidant and anticarcinogenic activities. Apparently, curcumin is not genotoxic in vivo, but in vitro copper and curcumin interactions induce genetic damage. The aim of this study was to test if in vivo copper excess induces DNA damage measured by comet and micronucleus assays in the presence of curcumin. We tested 0.2% curcumin in Balb-C mice at normal (13 ppm) and high (65, 130 and 390 ppm) copper ion concentrations. The comet and micronucleus assays were performed 48 hr after chemical application. Comet tail length in animals treated with 0.2% curcumin was not significantly different from the control. Animals exposed to copper cations (up to 390 ppm) exhibited higher oxidative DNA damage. Curcumin reduced the DNA damage induced by 390 ppm copper. We observed statistically significant increase in damage in individuals exposed to 390 ppm copper versus the control or curcumin groups, which was lowered by the presence of curcumin. Qualitative data on comets evidenced that cells from individuals exposed to 390 ppm copper had longer tails (categories 3 and 4) than in 390 ppm copper + curcumin. A statistically significant increase in frequency of micronucleated erythrocytes (MNE/10000TE) was observed only in 390 ppm copper versus the control and curcumin alone. Also cytotoxicity measured as the frequency of polychromatic erythrocytes (PE/1000TE) was attributable to 390 ppm copper. The lowest cytotoxic effect observed was attributed to curcumin. In vivo exposure to 0.2% curcumin for 48 hr did not cause genomic damage, while 390 ppm copper was genotoxic, but DNA damage induced by 390 ppm copper was diminished by curcumin. Curcumin seems to exert a genoprotective effect against DNA damage induced by high concentrations of copper cations. The comet and micronucleus assays prove to be suitable tools to detect DNA damage by copper in the presence of curcumin. PMID:17998598

  17. Chemopreventive effect of cactus Opuntia ficus indica on oxidative stress and genotoxicity of aflatoxin B1

    PubMed Central

    2011-01-01

    Background Aflatoxin B1 (AFB1) is potent hepatotoxic and hepatocarcinogenic agent. In aflatoxicosis, oxidative stress is a common mechanism contributing to initiation and progression of hepatic damage. The aim of this work was to evaluate the hepatoprotective effect of cactus cladode extract (CCE) on aflatoxin B1-induced liver damage in mice by measuring malondialdehyde (MDA) level, the protein carbonyls generation and the heat shock proteins Hsp 70 and Hsp 27 expressions in liver. We also looked for an eventual protective effect against AFB1-induced genotoxicity as determined by chromosome aberrations test, SOS Chromotest and DNA fragmentation assay. We further evaluated the modulation of p53, bax and bcl2 protein expressions in liver. Methods Adult, healthy balbC (20-25 g) male mice were pre-treated by intraperitonial administration of CCE (50 mg/Kg.b.w) for 2 weeks. Control animals were treated 3 days a week for 4 weeks by intraperitonial administration of 250 μg/Kg.b.w AFB1. Animals treated by AFB1 and CCE were divided into two groups: the first group was administrated CCE 2 hours before each treatment with AFB1 3 days a week for 4 weeks. The second group was administrated without pre-treatment with CCE but this extract was administrated 24 hours after each treatment with AFB1 3 days a week for 4 weeks. Results Our results clearly showed that AFB1 induced significant alterations in oxidative stress markers. In addition, it has a genotoxic potential and it increased the expression of pro apoptotic proteins p53 and bax and decreased the expression of bcl2. The treatment of CCE before or after treatment with AFB1, showed (i) a total reduction of AFB1 induced oxidative damage markers, (ii) an anti-genotoxic effect resulting in an efficient prevention of chromosomal aberrations and DNA fragmentation compared to the group treated with AFB1 alone (iii) restriction of the effect of AFB1 by differential modulation of the expression of p53 which decreased as well as its

  18. Antigenotoxic effect of green-synthesised silver nanoparticles from Ocimum sanctum leaf extract against cyclophosphamide induced genotoxicity in human lymphocytes—in vitro

    NASA Astrophysics Data System (ADS)

    Vijaya, P. P.; Rekha, B.; Mathew, Anu Thersa; Syed Ali, M.; Yogananth, N.; Anuradha, V.; Kalitha Parveen, P.

    2014-04-01

    The present study was aimed to identify the antigenotoxic effect of bio-synthesised silver nanoparticles (SNP) of Ocimum sanctum leaf extract against cyclophosphamide (CP). We tested the antigenotoxic effect of bio-synthesized silver nanoparticles of O. sanctum leaf extract on human lymphocytes against CP by using chromosomal aberration assay (CAA). Silver nanoparticles was first synthesized from fresh leaf extract of O. sanctum and characterised. Their quality was checked by XRD technique and morphology by SEM. Three different doses of the bio-synthesised SNPs namely, 50, 100 and 200 μl/ml were selected and CP (100 μg/ml) was used as a positive control for CAA. CP administration to human lymphocytes culture caused reduction in mitotic index (MI) and increase in chromosomal damages. The three doses (50, 100 and 200 μl/ml) significantly ( P < 0.005) reduced the chromosomal damages by CP and there was increase in MI. The biological way of synthesising SNPs has advantages like cost effectiveness and eco-friendly. Also the bio-synthesised SNPs of O. sanctum leaf extract was found to be an powerful genoprotectant. Furthermore works are to be carried out in future to find the extract mechanism of its genoprotective nature.

  19. Suppressive effect of post- or pre-treatment of aspirin metabolite on mitomycin C-induced genotoxicity using the somatic mutation and recombination test in Drosophila melanogaster.

    PubMed

    Niikawa, Miki; Shin, Seizai; Nagase, Hisamitsu

    2007-01-01

    In our previous paper, we found that aspirin suppressed in a somatic mutation and recombination test (SMART) of mitomycin C (MMC) in Drosophila melanogaster. In order to reveal the mechanism of bio-antimutagenicity and/or preventive effect of aspirin, we evaluated the suppressive ability of each aspirin metabolite, such as salicylic acid (SA), salicyluric acid (SUA), gentisic acid (GA), gentisuric acid (GUA) and 2,3-dihydroxybenzoic acid (DHBA), in SMART in D. melanogaster using post- and pre-treatments. As for the post-treatment, SA reduced the numbers of large single and twin spots. GA reduced the small single and large single spots, and GUA reduced the single spots, large single and twin spots. The inhibition of GUA is slightly stronger than that of any other metabolites; the inhibition percentage is 49 at the dose of 5 mg/bottle. On the other hand, as for the pre-treatment, aspirin, SUA, GA and DHBA reduced the numbers of small single spots. SUA, GE and DHBA reduced the number of large single spots. Aspirin and its metabolites did not reduce the number of twin spots. The results of the present study suggest that SA, GA and GUA repair or replicate DNA-damage by MMC and SUA, GA, GUA and DHBA prevent DNA-damage by MMC. It is suggested that secondary cancer is prevented by aspirin post-treatment without losing the medicinal effectiveness (anti-tumor activity). Therefore, we consider there are effective doses and/or administration timing of aspirin and MMC to prevent secondary cancer. PMID:17275250

  20. The in vitro genotoxic effect of Tucuma (Astrocaryum aculeatum), an Amazonian fruit rich in carotenoids.

    PubMed

    de Souza Filho, Olmiro Cezimbra; Sagrillo, Michele Rorato; Garcia, Luiz Filipe Machado; Machado, Alencar Kolinski; Cadoná, Francine; Ribeiro, Euler Esteves; Duarte, Marta Maria Medeiros Frescura; Morel, Ademir Farias; da Cruz, Ivana Beatrice Mânica

    2013-11-01

    Tucuma (Astrocaryum aculeatum) is an Amazonian fruit that presents high levels of carotenoids and other bioactive compounds such as quercetin. The extracts of tucuma peel and pulp present strong antioxidant activity which illustrate an elevated concentration that causes cytotoxic effects in human peripheral blood mononuclear cells (PBMCs). This study performed additional investigations to analyze the potential genotoxic effects of the tucuma extracts on PBMCs. The genotoxicity was evaluated by DNA fragmentation, Comet assay, and chromosomal instability G-band assays. The acute tucuma extract treatment showed genoprotective effects against DNA denaturation when compared with untreated PBMC cells. However, in the experiments with 24 and 72 h treatments to tucuma treatments, we observed low genotoxicity through a concentration of 100 μg/mL, some genotoxic effects related to intermediary concentrations (100-500 μg/mL), and more pronounced genotoxic effects on higher tucuma extract concentrations. After 24 h of treatment, the reactive oxygen species were similar among treatments and PBMC control groups. However, the caspase-1 activity related to the apoptosis and pyroptosis process increased significantly in higher tucuma concentrations. In summary, tucuma extracts, despite their higher antioxidant content and antioxidant activity, would present PBMCs genotoxic effects that are dependent on concentration and time exposition. These results need to be considered in future in vitro and in vivo studies of tucuma effects.

  1. Cytotoxic and genotoxic effects of multi-wall carbon nanotubes on human umbilical vein endothelial cells in vitro.

    PubMed

    Guo, Yuan-Yuan; Zhang, Jun; Zheng, Yi-Fan; Yang, Jun; Zhu, Xin-Qiang

    2011-04-01

    Carbon nanomaterials have multiple applications in various areas. However, it has been suggested that exposure to nanoparticles may be a risk for the development of vascular diseases due to injury and dysfunction of the vascular endothelium. Therefore, in the present study, the cytotoxic and genotoxic effects of multi-wall carbon nanotubes (MWCNTs) on human umbilical vein endothelial cells (HUVECs) were evaluated. Optical and transmission electronic microscopy (TEM) study showed that MWCNTs were able to enter cells rapidly, distribute in the cytoplasm and intracellular vesicles and induce morphological changes. Exposure to MWCNTs reduced the viability of HUVECs, and induced apoptosis in HUVECs. Furthermore, MWCNTs could cause DNA damage as indicated by the formation of γH2AX foci. MWCNTs also affected cellular redox status, e.g., increasing intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) levels, as well as altering superoxide dismutase (SOD) activity and glutathione peroxidase (GSH-Px) levels. On the other hand, the free radical scavenger N-acetyl-l-cysteine (NAC) preincubation can inhibit the cytotoxic and genotoxic effects of MWCNTs. Taken together, these results demonstrated that MWCNTs could induce cytotoxic and genotoxic effects in HUVECs, probably through oxidative damage pathways.

  2. Genotoxic effects of copper sulphate in freshwater planarian in vivo, studied with the single-cell gel test (comet assay).

    PubMed

    Guecheva, T; Henriques, J A; Erdtmann, B

    2001-10-18

    The alkaline single-cell gel electrophoresis, or comet assay, was used to evaluate the genotoxic potential of copper sulphate in planarians. Concentration-related increase in DNA damage was induced after 2h and 7 days exposure to CuSO4 dissolved in culture water. To study the influence of copper ions on the persistence of mutagen-induced DNA lesions, planarians were treated with methyl methanesulphonate (MMS), and further incubated in the absence (post-incubation) or presence (post-treatment) of CuSO4. After 2h of post-treatment enhanced persistence of DNA effects in relation to the corresponding post-incubation value was detected, which indicate inhibition of DNA repair by CuSO4. At 4h an increase of DNA migration in relation to the 2h value was observed, which is significant for the post-incubation group. After 24h, DNA damage decreased but was still significantly elevated in relation to the control. From our results, we conclude that planarians are suitable organisms for in vivo detection of copper genotoxicity in the comet assay, and can be used to assess both acute and chronic exposure to this chemical in aquatic ecosystems. The inhibition effect of copper ions on repair of MMS-induced DNA damage suggests that copper could modulate the genotoxic effects associated with complex mixture exposure in the environment.

  3. Genotoxicity of neutrons in Drosophila melanogaster. Somatic mutation and recombination induced by reactor neutrons.

    PubMed

    Guzmán-Rincón, J; Delfín-Loya, A; Ureña-Núñez, F; Paredes, L C; Zambrano-Achirica, F; Graf, U

    2005-08-01

    This paper describes the observation of a direct relationship between the absorbed doses of neutrons and the frequencies of somatic mutation and recombination using the wing somatic mutation and recombination test (SMART) of Drosophila melanogaster. This test was used for evaluating the biological effects induced by neutrons from the Triga Mark III reactor of Mexico. Two different reactor power levels were used, 300 and 1000 kW, and two absorbed doses were tested for each power level: 1.6 and 3.2 Gy for 300 kW and 0.84 and 1.7 Gy for 1000 kW. A linear relationship was observed between the absorbed dose and the somatic mutation and recombination frequencies. Furthermore, these frequencies were dependent on larval age: In 96-h-old larvae, the frequencies were increased considerably but the sizes of the spots were smaller than in 72-h-old larvae. The analysis of the balancer-heterozygous progeny showed a linear absorbed dose- response relationship, although the responses were clearly lower than found in the marker-trans-heterozygous flies. Approximately 65% of the genotoxicity observed is due to recombinational events. The results of the study indicate that thermal and fast neutrons are both mutagenic and recombinagenic in the D. melanogaster wing SMART, and that the frequencies are dependent on neutron dose, reactor power, and the age of the treated larvae.

  4. Genotoxicity of neutrons in Drosophila melanogaster. Somatic mutation and recombination induced by reactor neutrons.

    PubMed

    Guzmán-Rincón, J; Delfín-Loya, A; Ureña-Núñez, F; Paredes, L C; Zambrano-Achirica, F; Graf, U

    2005-08-01

    This paper describes the observation of a direct relationship between the absorbed doses of neutrons and the frequencies of somatic mutation and recombination using the wing somatic mutation and recombination test (SMART) of Drosophila melanogaster. This test was used for evaluating the biological effects induced by neutrons from the Triga Mark III reactor of Mexico. Two different reactor power levels were used, 300 and 1000 kW, and two absorbed doses were tested for each power level: 1.6 and 3.2 Gy for 300 kW and 0.84 and 1.7 Gy for 1000 kW. A linear relationship was observed between the absorbed dose and the somatic mutation and recombination frequencies. Furthermore, these frequencies were dependent on larval age: In 96-h-old larvae, the frequencies were increased considerably but the sizes of the spots were smaller than in 72-h-old larvae. The analysis of the balancer-heterozygous progeny showed a linear absorbed dose- response relationship, although the responses were clearly lower than found in the marker-trans-heterozygous flies. Approximately 65% of the genotoxicity observed is due to recombinational events. The results of the study indicate that thermal and fast neutrons are both mutagenic and recombinagenic in the D. melanogaster wing SMART, and that the frequencies are dependent on neutron dose, reactor power, and the age of the treated larvae. PMID:16038586

  5. Effects of konjac glucomannan, inulin and cellulose on acute colonic responses to genotoxic azoxymethane.

    PubMed

    Wu, Wen-Tzu; Yang, Lien-Chuan; Chen, Hsiao-Ling

    2014-07-15

    Mice were fed low-fibre, or that supplemented with soluble fibre (konjac glucomannan, KGM; inulin), or insoluble fibre (cellulose) to determine how these three fibres modulated the acute colonic responses to an azoxymethane (AOM) treatment. Results indicated that KGM and inulin exerted greater anti-genotoxic effects compared to cellulose and up-regulated the gene expressions of glutathione S-transferase and antioxidant enzymes. The apoptotic index in the distal colon was the greatest and the expression of Bcl-2 was the lowest in the KGM group 24h after the AOM treatment. On the other hand, the proliferative index and expression of Cyclin D1 were lower in all fibre groups. Furthermore, KGM increased cecal short-chain fatty acid contents, and both KGM and inulin increased fecal probiotic concentrations. This study suggested that soluble fibres were more effective than cellulose on ameliorating AOM-induced genotoxicity by up-regulating antioxidant enzyme genes, and enhancing epithelium apoptosis by down-regulating Bcl-2.

  6. The efficiacy of bismuth subnitrate against genotoxicity and oxidative stress induced by aluminum sulphate.

    PubMed

    Turkez, Hasan; Geyikoglu, Fatime

    2011-03-01

    Aluminum (Al) is commonly used in industrial processes and drugs and is thought to induce erythrocytes damage via activation of oxidative stress. Recently, bismuth (Bi)-containing drugs are used in the treatment of various diseases. However, uncertain effects of Bi in blood tissue may participate in the therapeutic efficacy of Bi compounds as related to metals. Hence, this study aimed to determine the roles on human blood cells of the various concentrations of aluminum sulphate (Al(2)(SO(4))(3)) and bismuth subnitrate (BSN), separate and together. With this aim, oxidative status was assessed on erythrocytes by measuring following oxidative stress markers: reduced glutathione (GSH), superoxide dismutase (SOD), glucose-6-phosphate dehydrogenase (G-6-PDH) and catalase (CAT). Two chemicals were tested for their ability to induce cytogenetic change in human lymphocytes using assays for chromosome aberrations (CAs) and sister chromatid exchanges (SCEs). Our results showed that high dose of Al(2)(SO(4))(3) (20 µg/mL) caused oxidative stress and increased CA and SCE frequencies. Whereas, BSN doses did not change CA and SCE rates. Moreover, it led to changes of antioxidant capacity at different concentrations. After concomitant treatment with Al(2)(SO(4))(3) and BSN, the effects of BSN doses were different on enzyme activities and decreased the genotoxic damage. However, the high dose of BSN and Al(2)(SO(4))(3) was shown to enhance the frequencies of CAs and SCEs in a synergistic manner. In conclusion, BSN could be effective in the protection against the blood toxicity of Al(2)(SO(4))(3).

  7. Evaluation of Genotoxic and Cytotoxic Effects in Human Peripheral Blood Lymphocytes Exposed In Vitro to Neonicotinoid Insecticides News

    PubMed Central

    Calderón-Segura, María Elena; Gómez-Arroyo, Sandra; Villalobos-Pietrini, Rafael; Martínez-Valenzuela, Carmen; Carbajal-López, Yolanda; Calderón-Ezquerro, María del Carmen; Cortés-Eslava, Josefina; García-Martínez, Rocío; Flores-Ramírez, Diana; Rodríguez-Romero, María Isabel; Méndez-Pérez, Patricia; Bañuelos-Ruíz, Enrique

    2012-01-01

    Calypso (thiacloprid), Poncho (clothianidin), Gaucho (imidacloprid), and Jade (imidacloprid) are commercial neonicotinoid insecticides, a new class of agrochemicals in México. However, genotoxic and cytotoxic studies have not been performed. In the present study, human peripheral blood lymphocytes (PBL) were exposed in vitro to different concentrations of the four insecticides. The genotoxic and cytotoxic effects were evaluated using the alkaline comet and trypan blue dye exclusion assays. DNA damage was evaluated using two genotoxicity parameters: tail length and comet frequency. Exposure to 9.5 × 10−6 to 5.7 × 10−5 M Jade; 2.8 × 10−4 to 1.7 × 10−3 M Gaucho; 0.6 × 10−1 to 1.4 × 10−1 M Calypso; 1.2 × 10−1 to 9.5 × 10−1 M Poncho for 2 h induced a significant increase DNA damage with a concentration-dependent relationship. Jade was the most genotoxic of the four insecticides studied. Cytotoxicity was observed in cells exposed to 18 × 10−3 M Jade, 2.0 × 10−3 M Gaucho, 2.0 × 10−1 M Calypso, 1.07 M Poncho, and cell death occurred at 30 × 10−3 M Jade, 3.3 × 10−3 M Gaucho, 2.8 × 10−1 M Calypso, and 1.42 M Poncho. This study provides the first report of genotoxic and cytotoxic effects in PBL following in vitro exposure to commercial neonicotinoid insecticides. PMID:22545045

  8. Genotoxicity Effects in Freshwater Fish from a Brazilian Impacted River.

    PubMed

    de Jesus, Isac Silva; Cestari, Marta Margarete; Bezerra, Marcos de Almeida; Affonso, Paulo Roberto Antunes de Mello

    2016-04-01

    This study evaluated the incidence of nuclear abnormalities (NA) in four fish species from an impacted river in Northeastern Brazil, characterized by accumulation of heavy metals and organic sewage. Two carnivores (Serrasalmus brandtii and Hoplias malabaricus) and two omnivore species (Oreochromis niloticus and Geophagus brasiliensis), used as food sources by local populations, were collected during the dry and the rainy season along Contas River basin. Nuclear abnormalities (bulbs, binuclei, lobes, micronuclei, notches, and vacuoles) were reported in all fish samples, with high occurrence in S. brandtii and H. malabaricus, species commonly found in local fish markets. This result agrees with previous analyses of accumulation of trace metals in both species, suggesting an association of genotoxic effects and biomagnification. Moreover, native specimens collected near urban areas presented higher frequencies of NA while O. niloticus seems to be more tolerant to environmental contamination. Therefore, effective policies are required to reduce the contamination of Contas River, since pollution by xenobiotics are potential threats to both local biodiversity and human population.

  9. Genotoxicity Effects in Freshwater Fish from a Brazilian Impacted River.

    PubMed

    de Jesus, Isac Silva; Cestari, Marta Margarete; Bezerra, Marcos de Almeida; Affonso, Paulo Roberto Antunes de Mello

    2016-04-01

    This study evaluated the incidence of nuclear abnormalities (NA) in four fish species from an impacted river in Northeastern Brazil, characterized by accumulation of heavy metals and organic sewage. Two carnivores (Serrasalmus brandtii and Hoplias malabaricus) and two omnivore species (Oreochromis niloticus and Geophagus brasiliensis), used as food sources by local populations, were collected during the dry and the rainy season along Contas River basin. Nuclear abnormalities (bulbs, binuclei, lobes, micronuclei, notches, and vacuoles) were reported in all fish samples, with high occurrence in S. brandtii and H. malabaricus, species commonly found in local fish markets. This result agrees with previous analyses of accumulation of trace metals in both species, suggesting an association of genotoxic effects and biomagnification. Moreover, native specimens collected near urban areas presented higher frequencies of NA while O. niloticus seems to be more tolerant to environmental contamination. Therefore, effective policies are required to reduce the contamination of Contas River, since pollution by xenobiotics are potential threats to both local biodiversity and human population. PMID:26894492

  10. Naringin, a grapefruit flavanone, protects V79 cells against the bleomycin-induced genotoxicity and decline in survival.

    PubMed

    Jagetia, Abhinav; Jagetia, Ganesh Chandra; Jha, Shalini

    2007-01-01

    The effect of naringin, a grapefruit flavonone was studied on bleomycin-induced genomic damage and alteration in the survival of cultured V79 cells. Exposure of V79 cells to bleomycin induced a concentration dependent elevation in the frequency of binucleate cells bearing micronuclei (MNBNC) and a maximum number of MNBNCs were observed in the cells treated with 50 microg ml(-1) bleomycin, the highest concentration evaluated. This genotoxic effect of bleomycin was reflected in the cell survival, where a concentration dependent decline was observed in the cells treated with different concentrations of bleomycin. Treatment of cells with 1 mm naringin before exposure to different concentrations of bleomycin arrested the bleomycin-induced decline in the cell survival accompanied by a significant reduction in the frequency of micronuclei when compared with bleomycin treatment alone. The cell survival and micronuclei induction were found to be inversely correlated. The repair kinetics of DNA damage induced by bleomycin was evaluated by exposing the cells to 10 microg ml(-1) bleomycin using single cell gel electrophoresis. Treatment of V79 cells with bleomycin resulted in a continuous increase in DNA damage up to 6 h post-bleomycin treatment as evident by migration of more DNA into the tails (% tail DNA) of the comets and a subsequent increase in olive tail moment (OTM), an index of DNA damage. Treatment of V79 cells with 1 mm naringin reduced bleomycin-induced DNA damage and accelerated DNA repair as indicated by a reduction in % tail DNA and OTM with increasing assessment time. A maximum reduction in the DNA damage was observed at 6 h post-bleomycin treatment, where it was 5 times lower than bleomycin alone. Our study, which was conducted on the basis of antioxidant, free radical scavenging and metal chelating properties of naringin demonstrates that naringin reduced the genotoxic effects of bleomycin and consequently increased the cell survival and therefore may act as

  11. Genotoxic effects of fumes from asphalt modified with waste plastic and tall oil pitch.

    PubMed

    Lindberg, Hanna K; Väänänen, Virpi; Järventaus, Hilkka; Suhonen, Satu; Nygren, Jonas; Hämeilä, Mervi; Valtonen, Jarkko; Heikkilä, Pirjo; Norppa, Hannu

    2008-05-31

    As the use of recycled materials and industrial by-products in asphalt mixtures is increasing, we investigated if recycled additives modify the genotoxicity of fumes emitted from asphalt. Fumes were generated in the laboratory at paving temperature from stone-mastic asphalt (SMA) and from SMA modified with waste plastic (90% polyethylene, 10% polypropylene) and tall oil pitch (SMA-WPT). In addition, fumes from SMA, SMA-WPT, asphalt concrete (AC), and AC modified with waste plastic and tall oil pitch (AC-WPT) were collected at paving sites. The genotoxicity of the fumes was studied by analysis of DNA damage (measured in the comet assay) and micronucleus formation in human bronchial epithelial BEAS 2B cells in vitro and by counting mutations in Salmonella typhimurium strains TA98 and YG1024. DNA damage was also assessed in buccal leukocytes from road pavers before and after working with SMA, SMA-WPT, AC, and AC-WPT. The chemical composition of the emissions was analysed by gas chromatography/mass spectrometry. The SMA-WPT fume generated in the laboratory induced a clear increase in DNA damage in BEAS 2B cells without metabolic activation. The laboratory-generated SMA fume increased the frequency of micronucleated BEAS 2B cells without metabolic activation. None of the asphalt fumes collected at the paving sites produced DNA damage with or without metabolic activation. Fumes from SMA and SMA-WPT from the paving sites increased micronucleus frequency without metabolic activation. None of the asphalt fumes studied showed mutagenic activity in Salmonella. No statistically significant differences in DNA damage in buccal leukocytes were detected between the pre- and post-shift samples collected from the road pavers. However, a positive correlation was found between DNA damage and the urinary metabolites of polycyclic aromatic hydrocarbons (PAHs) after work shift, which suggested an association between occupational exposures during road paving and genotoxic effects. Our

  12. Zinc oxide nanoparticles induced cyto- and genotoxicity in kidney epithelial cells.

    PubMed

    Uzar, Neslihan Kılıç; Abudayyak, Mahmut; Akcay, Namik; Algun, Gokhan; Özhan, Gül

    2015-01-01

    The wide uses of zinc oxide nanoparticles (nano-ZnO) in industrial, cosmetics, medicine, food production and electronics associate with increase in occupational and public exposure. Although, toxicity of nano-ZnO has been extensively studied on many different cell types and animal systems, there is a significant lack of toxicological data focus on nephrotoxic potential of nano-ZnO. In this study, the cyto- and genotoxic effects of nano-ZnO on rat kidney epithelial cells (NRK-52E) were investigated by using different assays. Nano-ZnO (10-50 nm of sizes) were synthesized by sol-gel method. For the cytotoxic effect of nano-ZnO, mean of inhibition concentration (IC50) values in cell line was evaluated by MTT, Trypan Blue (TB) and Neutral Red Uptake (NRU) assays at 25.0-100.0 μg/mL exposure concentrations. Nano-ZnO showed cytotoxic activity by acting on different targets in renal cells, with IC50 ≥ 73.05 μg/mL. Comet assay was used to evaluate the genotoxicity of nano-ZnO (12.5-50.0 μg/mL). Nano-ZnO caused statistically significant DNA damage. Our results highlight the important risk of cyto- and genotoxic effects of nano-ZnO over the kidney.

  13. Effects of chemical agent injections on genotoxicity of wastewater in a microfiltration-reverse osmosis membrane process for wastewater reuse.

    PubMed

    Tang, Fang; Hu, Hong-Ying; Wu, Qian-Yuan; Tang, Xin; Sun, Ying-Xue; Shi, Xiao-Lei; Huang, Jing-Jing

    2013-09-15

    With combined microfiltration (MF)/ultrafiltration (UF) and reverse osmosis (RO) process being widely used in municipal wastewater reclamation, RO concentrate with high level genotoxicity is becoming a potential risk to water environment. In this study, wastewater genotoxicity in a MF-RO process for municipal wastewater reclamation and also the effects of chemical agent injections were evaluated by SOS/umu genotoxicity test. The genotoxicity of RO concentrate ranged 500-559 μg 4-NQO (4-nitroquinoline-1-oxide)/L and 12-22 μg 4-NQO/mg DOC, was much higher than that of RO influent. Further research suggested that Kathon biocide was a key chemical agent associated with the genotoxicity increase. Kathon biocide used in RO system was highly genotoxic in vitro and Kathon biocide retained in RO system could contribute to a higher genotoxicity of RO concentrate. Hence, treatments for biocides before discharging are necessary. Chlorination of secondary effluent could significantly decrease the genotoxicity and increasing chlorine dosage could be an efficacious method to decrease the genotoxicity of RO concentrate. According to the result of the experiment, the dosage of chlorine in dual-membrane process could be set to about 2.5 mg Cl₂/L. The effect of antiscalant (2-phosphomobutane-1,2,4-tricarboxylic acid) was also investigated; it turned out to have no effect on genotoxicity.

  14. Nitroxide TEMPO: a genotoxic and oxidative stress inducer in cultured cells.

    PubMed

    Guo, Xiaoqing; Mittelstaedt, Roberta A; Guo, Lei; Shaddock, Joseph G; Heflich, Robert H; Bigger, Anita H; Moore, Martha M; Mei, Nan

    2013-08-01

    2,2,6,6-Tetramethylpiperidine-1-oxyl (TEMPO) is a low molecular weight nitroxide and stable free radical. In this study, we investigated the cytotoxicity and genotoxicity of TEMPO in mammalian cells using the mouse lymphoma assay (MLA) and in vitro micronucleus assay. In the absence of metabolic activation (S9), 3mM TEMPO produced significant cytotoxicity and marginal mutagenicity in the MLA; in the presence of S9, treatment of mouse lymphoma cells with 1-2mM TEMPO resulted in dose-dependent decreases of the relative total growth and increases in mutant frequency. Treatment of TK6 human lymphoblastoid cells with 0.9-2.3mM TEMPO increased the frequency of both micronuclei (a marker for clastogenicity) and hypodiploid nuclei (a marker of aneugenicity) in a dose-dependent manner; greater responses were produced in the presence of S9. Within the dose range tested, TEMPO induced reactive oxygen species and decreased glutathione levels in mouse lymphoma cells. In addition, the majority of TEMPO-induced mutants had loss of heterozygosity at the Tk locus, with allele loss of ⩽34Mbp. These results indicate that TEMPO is mutagenic in the MLA and induces micronuclei and hypodiploid nuclei in TK6 cells. Oxidative stress may account for part of the genotoxicity induced by TEMPO in both cell lines.

  15. Determination of cytotoxic and genotoxic effects of naphthalene, 1-naphthol and 2-naphthol on human lymphocyte culture.

    PubMed

    Kapuci, Mete; Ulker, Zeynep; Gurkan, Sezin; Alpsoy, Lokman

    2014-02-01

    Naphthalene, a bicyclic aromatic hydrocarbon, has toxic effects on animals and humans. Although recent studies stressed on the genotoxic and cytotoxic effects of naphthalene and its metabolites on eukaryotic cells, there is a big controversy among the results of these studies. The aim of this study is to investigate the effects of naphthalene and its metabolites on the cytotoxicity and genotoxicity in the human lymphocytes in the culture. The genotoxic and cytotoxic effects of naphthalene and its metabolites, 1-naphthol and 2-naphthol, were studied using cytotoxicity test (lactate dehydrogenase and cell proliferation (WST-1) assays) and DNA fragmentation assay (terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay). Naphthalene and its metabolites had no significant cytotoxic effect on treated samples when compared with untreated ones. This result was also confirmed by WST-1 assay. In the TUNEL assay, DNA fragmentation was induced significantly by all concentrations of naphthalene and 2-naphthol and 50 and 100 µM concentrations of 1-naphthol (p < 0.05 or 0.001). In the DNA fragmentation, the most effective dose of 2-naphthol (63%) was 100 µM, when compared with negative control group (13%). These results suggest that naphthalene and its metabolites, 1-naphthol and 2-naphthol, may cause DNA damage on human lymphocytes.

  16. Lead-induced genotoxicity to Vicia faba L. roots in relation with metal cell uptake and initial speciation.

    PubMed

    Shahid, M; Pinelli, E; Pourrut, B; Silvestre, J; Dumat, C

    2011-01-01

    Formation of organometallic complexes in soil solution strongly influence metals phytoavailability. However, only few studies deal with the influence of metal speciation both on plant uptake and genotoxicity. In the present study, Vicia faba seedlings were exposed for 6h in controlled hydroponic conditions to 5 μM of lead nitrate alone and chelated to varying degrees by different organic ligands. Ethylenediaminetetraacetic acid and citric acid were, respectively, chosen as models of humic substances and low weight organic acids present in natural soil solutions. Visual Minteq software was used to estimate free lead cations concentration and ultimately to design the experimental layout. For all experimental conditions, both micronucleus test and measure of lead uptake by plants were finally performed. Chelation of Pb by EDTA, a strong chelator, dose-dependently increased the uptake in V. faba roots while its genotoxicity was significantly reduced, suggesting a protective role of EDTA. A weak correlation was observed between total lead concentration absorbed by roots and genotoxicity (r(2)=0.65). In contrast, a strong relationship (r(2)=0.93) exists between Pb(2+) concentration in exposure media and genotoxicity in the experiment performed with EDTA. Citric acid induced labile organometallic complexes did not demonstrate any significant changes in lead genotoxicity or uptake. These results demonstrate that metal speciation knowledge could improve the interpretation of V. faba genotoxicity test performed to test soil quality.

  17. Acute dyskerin depletion triggers cellular senescence and renders osteosarcoma cells resistant to genotoxic stress-induced apoptosis

    SciTech Connect

    Lin, Ping; Mobasher, Maral E.; Alawi, Faizan

    2014-04-18

    Highlights: • Dyskerin depletion triggers cellular senescence in U2OS osteosarcoma cells. • Dyskerin-depleted cells are resistant to apoptosis induced by genotoxic stress. • Chromatin relaxation sensitizes dyskerin-depleted cells to apoptosis. - Abstract: Dyskerin is a conserved, nucleolar RNA-binding protein implicated in an increasing array of fundamental cellular processes. Germline mutation in the dyskerin gene (DKC1) is the cause of X-linked dyskeratosis congenita (DC). Conversely, wild-type dyskerin is overexpressed in sporadic cancers, and high-levels may be associated with poor prognosis. It was previously reported that acute loss of dyskerin function via siRNA-mediated depletion slowed the proliferation of transformed cell lines. However, the mechanisms remained unclear. Using human U2OS osteosarcoma cells, we show that siRNA-mediated dyskerin depletion induced cellular senescence as evidenced by proliferative arrest, senescence-associated heterochromatinization and a senescence-associated molecular profile. Senescence can render cells resistant to apoptosis. Conversely, chromatin relaxation can reverse the repressive effects of senescence-associated heterochromatinization on apoptosis. To this end, genotoxic stress-induced apoptosis was suppressed in dyskerin-depleted cells. In contrast, agents that induce chromatin relaxation, including histone deacetylase inhibitors and the DNA intercalator chloroquine, sensitized dyskerin-depleted cells to apoptosis. Dyskerin is a core component of the telomerase complex and plays an important role in telomere homeostasis. Defective telomere maintenance resulting in premature senescence is thought to primarily underlie the pathogenesis of X-linked DC. Since U2OS cells are telomerase-negative, this leads us to conclude that loss of dyskerin function can also induce cellular senescence via mechanisms independent of telomere shortening.

  18. Mechanistic evaluation of Ginkgo biloba leaf extract-induced genotoxicity in L5178Y cells.

    PubMed

    Lin, Haixia; Guo, Xiaoqing; Zhang, Suhui; Dial, Stacey L; Guo, Lei; Manjanatha, Mugimane G; Moore, Martha M; Mei, Nan

    2014-06-01

    Ginkgo biloba has been used for many thousand years as a traditional herbal remedy and its extract has been consumed for many decades as a dietary supplement. Ginkgo biloba leaf extract is a complex mixture with many constituents, including flavonol glycosides and terpene lactones. The National Toxicology Program 2-year cancer bioassay found that G. biloba leaf extract targets the liver, thyroid gland, and nose of rodents; however, the mechanism of G. biloba leaf extract-associated carcinogenicity remains unclear. In the current study, the in vitro genotoxicity of G. biloba leaf extract and its eight constituents was evaluated using the mouse lymphoma assay (MLA) and Comet assay. The underlying mechanisms of G. biloba leaf extract-associated genotoxicity were explored. Ginkgo biloba leaf extract, quercetin, and kaempferol resulted in a dose-dependent increase in the mutant frequency and DNA double-strand breaks (DSBs). Western blot analysis confirmed that G. biloba leaf extract, quercetin, and kaempferol activated the DNA damage signaling pathway with increased expression of γ-H2AX and phosphorylated Chk2 and Chk1. In addition, G. biloba leaf extract produced reactive oxygen species and decreased glutathione levels in L5178Y cells. Loss of heterozygosity analysis of mutants indicated that G. biloba leaf extract, quercetin, and kaempferol treatments resulted in extensive chromosomal damage. These results indicate that G. biloba leaf extract and its two constituents, quercetin and kaempferol, are mutagenic to the mouse L5178Y cells and induce DSBs. Quercetin and kaempferol likely are major contributors to G. biloba leaf extract-induced genotoxicity.

  19. FOLATE DEFICIENCY ENHANCES ARSENIC-INDUCED GENOTOXICITY IN MICE

    EPA Science Inventory

    Folate deficiency increases background levels of DNA damage and can enhance the mutagenicity of chemical agents. Duplicate experiments were performed to investigate the effect of dietary folate deficiency on arsenic induction of micronuclei (MN) in peripheral blood cells. Male C5...

  20. Long-term exposures to low doses of titanium dioxide nanoparticles induce cell transformation, but not genotoxic damage in BEAS-2B cells.

    PubMed

    Vales, Gerard; Rubio, Laura; Marcos, Ricard

    2015-01-01

    There is a great interest in a better knowledge of the health effects caused by nanomaterials exposures and, in particular to those induced by titanium dioxide nanoparticles (nano-TiO2) due to its high use and increasing presence in the environment. To add new information on its potential genotoxic/carcinogenic risk, we have carried out experiments using chronic exposures (up to 4 weeks), low doses, and the BEAS-2B cell line that, as a human bronchial epithelium cells, can be considered a good cell target. Cell uptake has been assessed by transmission electron microscopy (TEM) and flow cytometry (FC); genotoxicity was evaluated using the comet and the micronucleus (MN) assays; and cell-transforming ability was evaluated using the soft-agar assay to detect anchorage-independent cell growth. Results show an important cell uptake at all the tested doses and sampling times used (except for 1 µg/mL and 24-h exposure). Nevertheless, no genotoxic effects were observed in the comet and in the MN assays. This lack of genotoxic effect agrees with the FC results showing no induction of intracellular reactive oxygen species (ROS), the data from the comet assay with formamidopyrimidine DNA glycosylase (FPG) enzyme showing no induction of oxidized bases, and the lack of induction of expression of heme-oxygenase (HO-1) gene both at the RNA and protein level. On the contrary, significant increases in the number of clones growing in an anchorage-independent way were observed. This study would indicate a potential carcinogenic risk associated to nano-TiO2 exposure, not mediated by a genotoxic mechanism.

  1. Dietary elevated sucrose modulation of diesel-induced genotoxicity in the colon and liver of Big Blue rats.

    PubMed

    Risom, Lotte; Møller, Peter; Hansen, Max; Autrup, Herman; Bornholdt, Jette; Vogel, Ulla; Wallin, Håkan; Poulsen, Henrik E; Dragsted, Lars O; Loft, Steffen

    2003-11-01

    Earlier studies have indicated that sucrose possesses either co-carcinogenic or tumor-promoter effects in colon carcinogenesis induced by genotoxic carcinogens. In this study we investigated the role of sucrose on diesel exhaust particle (DEP)-induced genotoxicity in the colonic mucosa and liver. Big Blue rats were fed with DEP (0.8 ppm in feed) and/or sucrose (3.45% or 6.85% w/w in feed) for 3 weeks. DEP increased both DNA strand breaks and DNA adducts in colon. Interestingly, sucrose also increased the level of bulky DNA adducts in colon. DEP and sucrose had no effect on DNA strand-breaks and DNA adducts in liver. DEP and sucrose treatment did not have any effect on mutation frequency in colon and liver. Oxidative DNA damage detected as 8-oxodG (8-oxo-7,8-dihydro-2'-deoxyguanosine) and endonuclease III or formamidopyrimidine DNA glycosylase sensitive sites was unaltered in colon and liver. The mRNA expression levels of the DNA repair enzymes N-methylpurine DNA glycosylase ( MPG), 8-oxoguanine DNA glycosylase ( OGG1) and ERCC1 (part of the nucleotide excision repair complex) measured by reverse transcription-polymerase chain reaction were increased in liver by DEP feeding. In colon, expression was unaffected by DEP or sucrose feeding. Among biomarkers of oxidative stress, including vitamin C, malondialdehyde and protein oxidations (gamma-glutamyl semialdehyde and 2-amino adipic semialdehyde) in plasma and liver, only malondialdehyde was increased in plasma by sucrose/DEP feeding. In conclusion, sucrose feeding did not increase DEP-induced DNA damage in colon or liver. PMID:12937889

  2. The Genotoxic and Cytotoxic Effects of Bisphenol-A (BPA) in MCF-7 Cell Line and Amniocytes

    PubMed Central

    Aghajanpour-Mir, Seyed Mohsen; Zabihi, Ebrahim; Akhavan-Niaki, Haleh; Keyhani, Elahe; Bagherizadeh, Iman; Biglari, Sajjad; Behjati, Farkhondeh

    2016-01-01

    Bisphenol-A (BPA) is an industrial xenoestrogen used widely in our living environment. Recently, several studies suggested that BPA has destructive effects on DNA and chromosomes in normal body cells via estrogen receptors (ER). Therefore, BPA could be considered as an important mediator in many diseases such as cancer. However, there are still many controversial issues which need clarification. In this study, we investigated the BPA-induced chromosomal damages in MCF-7 cell line, ER-positive and negative amniocyte cells. Cytotoxicity and genotoxicity effects of BPA were also compared between these three cell groups. Expression of estrogen receptors was determined using immunocytochemistry technique. The cell cytotoxicity of BPA was measured by MTT assay. Classic cytogenetic technique was carried out for the investigation of chromosome damage. BPA, in addition to cytotoxicity, had remarkable genotoxicity at concentrations close to the traceable levels in tissues or biological fluids. Although some differences were observed in the amount of damages between ER-positive and negative fetal cells, interestingly, these differences were not significant. The present study showed that BPA could lead to chromosomal aberrations in both ER-dependent and independent pathways at some concentrations or in cell types yet not reported. Also, BPA could probably be considered as a facilitator for some predisposed cells to be cancerous by raising the chromosome instability levels. Finally, estrogen receptor seems to have a different role in cytotoxicity and genotoxicity effects. PMID:27386435

  3. The Genotoxic and Cytotoxic Effects of Bisphenol-A (BPA) in MCF-7 Cell Line and Amniocytes.

    PubMed

    Aghajanpour-Mir, Seyed Mohsen; Zabihi, Ebrahim; Akhavan-Niaki, Haleh; Keyhani, Elahe; Bagherizadeh, Iman; Biglari, Sajjad; Behjati, Farkhondeh

    2016-01-01

    Bisphenol-A (BPA) is an industrial xenoestrogen used widely in our living environment. Recently, several studies suggested that BPA has destructive effects on DNA and chromosomes in normal body cells via estrogen receptors (ER). Therefore, BPA could be considered as an important mediator in many diseases such as cancer. However, there are still many controversial issues which need clarification. In this study, we investigated the BPA-induced chromosomal damages in MCF-7 cell line, ER-positive and negative amniocyte cells. Cytotoxicity and genotoxicity effects of BPA were also compared between these three cell groups. Expression of estrogen receptors was determined using immunocytochemistry technique. The cell cytotoxicity of BPA was measured by MTT assay. Classic cytogenetic technique was carried out for the investigation of chromosome damage. BPA, in addition to cytotoxicity, had remarkable genotoxicity at concentrations close to the traceable levels in tissues or biological fluids. Although some differences were observed in the amount of damages between ER-positive and negative fetal cells, interestingly, these differences were not significant. The present study showed that BPA could lead to chromosomal aberrations in both ER-dependent and independent pathways at some concentrations or in cell types yet not reported. Also, BPA could probably be considered as a facilitator for some predisposed cells to be cancerous by raising the chromosome instability levels. Finally, estrogen receptor seems to have a different role in cytotoxicity and genotoxicity effects. PMID:27386435

  4. The Genotoxic and Cytotoxic Effects of Bisphenol-A (BPA) in MCF-7 Cell Line and Amniocytes.

    PubMed

    Aghajanpour-Mir, Seyed Mohsen; Zabihi, Ebrahim; Akhavan-Niaki, Haleh; Keyhani, Elahe; Bagherizadeh, Iman; Biglari, Sajjad; Behjati, Farkhondeh

    2016-01-01

    Bisphenol-A (BPA) is an industrial xenoestrogen used widely in our living environment. Recently, several studies suggested that BPA has destructive effects on DNA and chromosomes in normal body cells via estrogen receptors (ER). Therefore, BPA could be considered as an important mediator in many diseases such as cancer. However, there are still many controversial issues which need clarification. In this study, we investigated the BPA-induced chromosomal damages in MCF-7 cell line, ER-positive and negative amniocyte cells. Cytotoxicity and genotoxicity effects of BPA were also compared between these three cell groups. Expression of estrogen receptors was determined using immunocytochemistry technique. The cell cytotoxicity of BPA was measured by MTT assay. Classic cytogenetic technique was carried out for the investigation of chromosome damage. BPA, in addition to cytotoxicity, had remarkable genotoxicity at concentrations close to the traceable levels in tissues or biological fluids. Although some differences were observed in the amount of damages between ER-positive and negative fetal cells, interestingly, these differences were not significant. The present study showed that BPA could lead to chromosomal aberrations in both ER-dependent and independent pathways at some concentrations or in cell types yet not reported. Also, BPA could probably be considered as a facilitator for some predisposed cells to be cancerous by raising the chromosome instability levels. Finally, estrogen receptor seems to have a different role in cytotoxicity and genotoxicity effects.

  5. Titanium dioxide nanoparticles induce genotoxicity but not mutagenicity in golden mussel Limnoperna fortunei.

    PubMed

    Girardello, Francine; Custódio Leite, Camila; Vianna Villela, Izabel; da Silva Machado, Miriana; Luiz Mendes Juchem, André; Roesch-Ely, Mariana; Neves Fernandes, Andreia; Salvador, Mirian; Antonio Pêgas Henriques, João

    2016-01-01

    The widespread use of titanium dioxide nanoparticles (TiO2-NP) in consumer products is the cause of its appearance in wastewater and effluents, reaching the aquatic environment. The evaluation of the biological impact of TiO2-NP and the need to understand its ecotoxicological impact to the aquatic ecosystem are of major concern. Bivalve mollusks may represent a target group for nanoparticle toxicity. Limnoperna fortunei (golden mussel), a freshwater bivalve organism that has been employed in biomonitoring environmental conditions. Comet assay, micronucleus test and oxidative damage to lipids and proteins were performed after the golden mussel was exposed to TiO2-NP (1, 5, 10 and 50μgmL(-1)). The results demonstrate that TiO2-NP can damage the DNA of haemocytes after 2h of exposure and the genotoxic activity significantly increased after 4h exposure to TiO2-NP, at all the TiO2-NP concentrations. TiO2-NP was ineffective in causing mutagenicity in the haemolymph cells of golden mussel. The increase in the lipid peroxidation levels and carbonyl proteins after the exposure to TiO2-NP indicates the induction of oxidative stress at 2h exposure with similar results to all TiO2-NP concentrations, but these effects did not occur at 4h exposure. These results demonstrated that, although TiO2-NP is not mutagenic to golden mussel, it does induce DNA damage and oxidative stress in these organisms.

  6. Titanium dioxide nanoparticles induce genotoxicity but not mutagenicity in golden mussel Limnoperna fortunei.

    PubMed

    Girardello, Francine; Custódio Leite, Camila; Vianna Villela, Izabel; da Silva Machado, Miriana; Luiz Mendes Juchem, André; Roesch-Ely, Mariana; Neves Fernandes, Andreia; Salvador, Mirian; Antonio Pêgas Henriques, João

    2016-01-01

    The widespread use of titanium dioxide nanoparticles (TiO2-NP) in consumer products is the cause of its appearance in wastewater and effluents, reaching the aquatic environment. The evaluation of the biological impact of TiO2-NP and the need to understand its ecotoxicological impact to the aquatic ecosystem are of major concern. Bivalve mollusks may represent a target group for nanoparticle toxicity. Limnoperna fortunei (golden mussel), a freshwater bivalve organism that has been employed in biomonitoring environmental conditions. Comet assay, micronucleus test and oxidative damage to lipids and proteins were performed after the golden mussel was exposed to TiO2-NP (1, 5, 10 and 50μgmL(-1)). The results demonstrate that TiO2-NP can damage the DNA of haemocytes after 2h of exposure and the genotoxic activity significantly increased after 4h exposure to TiO2-NP, at all the TiO2-NP concentrations. TiO2-NP was ineffective in causing mutagenicity in the haemolymph cells of golden mussel. The increase in the lipid peroxidation levels and carbonyl proteins after the exposure to TiO2-NP indicates the induction of oxidative stress at 2h exposure with similar results to all TiO2-NP concentrations, but these effects did not occur at 4h exposure. These results demonstrated that, although TiO2-NP is not mutagenic to golden mussel, it does induce DNA damage and oxidative stress in these organisms. PMID:26675368

  7. Mercury heavy-metal-induced physiochemical changes and genotoxic alterations in water hyacinths [Eichhornia crassipes (Mart.)].

    PubMed

    Malar, Srinivasan; Sahi, Shivendra Vikram; Favas, Paulo J C; Venkatachalam, Perumal

    2015-03-01

    Mercury heavy metal pollution has become an important environmental problem worldwide. Accumulation of mercury ions by plants may disrupt many cellular functions and block normal growth and development. To assess mercury heavy metal toxicity, we performed an experiment focusing on the responses of Eichhornia crassipes to mercury-induced oxidative stress. E. crassipes seedlings were exposed to varying concentrations of mercury to investigate the level of mercury ions accumulation, changes in growth patterns, antioxidant defense mechanisms, and DNA damage under hydroponics system. Results showed that plant growth rate was significantly inhibited (52 %) at 50 mg/L treatment. Accumulation of mercury ion level were 1.99 mg/g dry weight, 1.74 mg/g dry weight, and 1.39 mg/g dry weight in root, leaf, and petiole tissues, respectively. There was a decreasing trend for chlorophyll a, b, and carotenoids with increasing the concentration of mercury ions. Both the ascorbate peroxidase and malondialdehyde contents showed increased trend in leaves and roots up to 30 mg/L mercury treatment and slightly decreased at the higher concentrations. There was a positive correlation between heavy metal dose and superoxide dismutase, catalase, and peroxidase antioxidative enzyme activities which could be used as biomarkers to monitor pollution in E. crassipes. Due to heavy metal stress, some of the normal DNA bands were disappeared and additional bands were amplified compared to the control in the random amplified polymorphic DNA (RAPD) profile. Random amplified polymorphic DNA results indicated that genomic template stability was significantly affected by mercury heavy metal treatment. We concluded that DNA changes determined by random amplified polymorphic DNA assay evolved a useful molecular marker for detection of genotoxic effects of mercury heavy metal contamination in plant species.

  8. Influence of Mikania laevigata Extract over the Genotoxicity Induced by Alkylating Agents

    PubMed Central

    Nicolau, Vanessa; de Aguiar Amaral, Patrícia; de Andrade, Vanessa Moraes

    2013-01-01

    Medicinal plants are still widely used worldwide; yet for some species, little or no information is available concerning their biological activity, specially their genotoxic and antimutagenic potential. Mikania laevigata (Asteraceae) is a native plant from South America, and its extracts are largely used to treat respiratory complaints. The aim of the present work was then to evaluate, in vivo, the potential biological activity of M. laevigata on the genotoxicity induced by methyl methanesulfonate (MMS) and cyclophosphamide (CP), using the comet assay. Male CF1 mice were divided into groups of 5-6 animals, received by gavage 0.1 mL/10 g body wt of water, Mikania laevigata extract (MLE), MMS, and CP. Results showed that treatment with 200 mg/kg of the MLE previously to MMS and CP administration, respectively, reduced the damage index (DI) in 52% and 60%, when compared to DI at 24 h. Pretreatment also reduced the damage frequency (DF) in 56% (MMS) and 58% (CP), compared to DF at 24 h. MLE administration has been shown to protect mouse DNA from damage induced by alkylating agents; this corroborates to the biological activities of M. laevigata and points towards the need of plant compounds isolation to proceed with further studies. PMID:23724299

  9. Effect of organic tomato (Lycopersicon esculentum) extract on the genotoxicity of doxorubicin in the Drosophila wing spot test

    PubMed Central

    2009-01-01

    The consumption of organic tomatoes (ORTs) reduces the risk of harmful effects to humans and the environment caused by exposure to toxic agrochemicals. In this study, we used the somatic mutation and recombination test (SMART) of wing spots in Drosophila melanogaster to evaluate the genotoxicity of ORT and the effect of cotreatment with ORT on the genotoxicity of Doxorubicin® (DXR, a cancer chemotherapeutic agent) that is mediated by free radical formation. Standard (ST) cross larvae were treated chronically with solutions containing 25%, 50% or 100% of an aqueous extract of ORT, in the absence and presence of DXR (0.125 mg/mL), and the number of mutant spots on the wings of emergent flies was counted. ORT alone was not genotoxic but enhanced the toxicity of DXR when administered concomitantly with DXR. The ORT-enhanced frequency of spots induced by DXR may have resulted from the interaction of ORT with the enzymatic systems that catalyze the metabolic detoxification of this drug. PMID:21637658

  10. Genotoxic effects of the insecticide cypermethrin on the root meristem cells of sunflowers (Helianthus annuus L.).

    PubMed

    Inceer, Huseyin; Hayirlioglu-Ayaz, Sema; Ozcan, Melahat

    2009-11-01

    In this study, the genotoxic effects of the insecticide cypermethrin on the root meristem cells of sunflowers (Helianthus annuus L.) were investigated. The roots were treated with 10- 25- 50- and 100-ppm concentrations of cypermethrin for 6, 12 and 24 h. The mitotic index and mitotic abnormalities were determined in both control and test groups. The cypermethrin showed a marked mitodepressive action on mitosis. The types of mitotic abnormalities included disturbed metaphase, c-mitosis, stickiness, laggards and chromatid bridges. A pronounced toxic effect was observed at the 50-ppm concentration. Cypermethrin may have genotoxic effects on sunflowers.

  11. Genotoxic damage of benzo[a]pyrene in cultured sea bream (Sparus aurata L.) hepatocytes: harmful effects of chronic exposure.

    PubMed

    Pastore, Anna Selene; Santacroce, Maria Pia; Narracci, Marcella; Cavallo, Rosa Anna; Acquaviva, Maria Immacolata; Casalino, Elisabetta; Colamonaco, Michele; Crescenzo, Giuseppe

    2014-09-01

    The large majority of studies on the genotoxic hazard of PAHs polluted water widely applied the ENA assay as versatile tool in large number of wild and farmed aquatic species. Nuclear abnormalities are commonly considered to be a direct consequence of genotoxic lesions in DNA macromolecule, and such evaluation might be helpful in identifying the genotoxic damage induced by the most harmful PAHs such as B[a]P. Regarding at the fish species subjected to aquaculture, most of the toxicological data come from wild fish and mainly focus on freshwater fish, but very little is known for other marine major aquacultured species. The gilthead sea bream (Sparus aurata L.) is the most economically important sparid species cultured along the Mediterranean costs, and it has been proved a very sensitive species to acute B[a]P exposure. However, further investigation is needed on several other types of genotoxic assessments, especially for chronic effects. This work was totally based on an in vitro model for chronic toxicity, using long-term S. aurata hepatocytes in primary culture, continuously exposed to low levels of BaP, over a prolonged period of time, to provide evidences for latent toxicity response. We aimed to investigate the kind of nuclear damage in gilthead sea bream hepatocytes continuously exposed to B[a]P sublethal doses. Cells were exposed to several B[a]P concentrations (10 μg/mL, 1 μg/mL, 1 ng/mL, 1 pg/mL) for two exposure times (24 and 72 h), and then tested both for apoptosis induction and for nuclear abnormalities by immunofluorescence analysis. The presence of severe nuclear damage, revealed cells progressing towards abnormal genotypes, due to a series of aberrant mitosis followed by unequal distribution of chromosomal content. The nuclear atypia (NA) more frequently observed were: a) micronuclei (MN); b) nuclear buds or blebs (NBUDs); c) notched nuclei; d) lobed nuclei; e) nuclei with nucleoplasmic bridge (NPBs); f) nuclei squashed, with a residual

  12. Effects of paving asphalt fume exposure on genotoxic and mutagenic activities in the rat lung.

    PubMed

    Zhao, H W; Yin, X J; Frazer, D; Barger, M W; Siegel, P D; Millecchia, L; Zhong, B Z; Tomblyn, S; Stone, S; Ma, J K H; Castranova, V; Ma, J Y C

    2004-02-14

    Asphalt fumes are complex mixtures of aerosols and vapors containing various organic compounds, including polycyclic aromatic hydrocarbons (PAHs). Previously, we have demonstrated that inhalation exposure of rats to asphalt fumes resulted in dose-dependent induction of CYP1A1 with concomitant down-regulation of CYP2B1 and increased phase II enzyme quinone reductase activity in the rat lung. In the present study, the potential genotoxic effects of asphalt fume exposure due to altered lung microsomal enzymes were studied. Rats were exposed to air or asphalt fume generated under road paving conditions at various concentrations and sacrificed the next day. Alveolar macrophages (AM) were obtained by bronchoalveolar lavage and examined for DNA damage using the comet assay. To evaluate the systemic genotoxic effect of asphalt fume, micronuclei formation in bone marrow polychromatic erythrocytes (PCEs) was monitored. Lung S9 from various exposure groups was isolated from tissue homogenates and characterized for metabolic activity in activating 2-aminoanthracene (2-AA) and benzo[a]pyrene (BaP) mutagenicity using the Ames test with Salmonella typhimurium YG1024 and YG1029. This study showed that the paving asphalt fumes significantly induced DNA damage in AM, as revealed by DNA migration in the comet assay, in a dose-dependent manner, whereas the micronuclei formation in bone marrow PCEs was not detected even at a very high exposure level (1733 mg h/m3). The conversion of 2-AA to mutagens in the Ames test required lung S9-mediated metabolic activation in a dose-dependent manner. In comparison to the controls, lung S9 from rats exposed to asphalt fume at a total exposure level of 479+/-33 mg h/m3 did not significantly enhance 2-AA mutagenicity with either S. typhimurium YG1024 or YG1029. At a higher total asphalt fume exposure level (1150+/-63 mg h/m3), S9 significantly increased the mutagenicity of 2-AA as compared to the control. However, S9 from asphalt fume-exposed rats

  13. Genotoxic effect of Lythrum salicaria extract determined by the mussel micronucleus test.

    PubMed

    Eck-Varanka, Bettina; Kováts, Nóra; Hubai, Katalin; Paulovits, Gábor; Ferincz, Árpád; Horváth, Eszter

    2015-12-01

    A wide range of aquatic plants have been proven to release allelochemicals, of them phenolics and tannin are considered rather widely distributed. Tannins, however, have been demonstrated to have genotoxic capacity. In our study genotoxic potential of Lythrum salicaria L. (Purple Loosestrife, family Lythraceae) was assessed by the mussel micronucleus test, using Unio pictorum. In parallel, total and hydrolysable tannin contents were determined. Results clearly show that the extract had a high hydrolysable tannin content and significant mutagenic effect. As L. salicaria has been long used in traditional medicine for chronic diarrhoea, dysentery, leucorrhoea and blood-spitting, genotoxic potential of the plant should be evaluated not only with regard to potential effects in the aquatic ecosystem, but also assessing its safe use as a medicinal herb.

  14. Deoxynivalenol induced oxidative stress and genotoxicity in human peripheral blood lymphocytes.

    PubMed

    Yang, Wei; Yu, Miao; Fu, Juan; Bao, Wei; Wang, Di; Hao, Liping; Yao, Ping; Nüssler, Andreas K; Yan, Hong; Liu, Liegang

    2014-02-01

    Deoxynivalenol (DON) is one of the most common mycotoxins. The aim of this study consists in using diverse cellular and molecular assays to evaluate cytotoxicity, genotoxicity as well as oxidative damage and to investigate their mechanisms in human peripheral blood lymphocytes. The human lymphocytes were cultured in eight different doses of DON (0, 6.25, 12.5, 25, 50, 100, 250 and 500 ng/mL) during 6, 12 and 24 h. DON was able to decrease cell viability and cause damage to the membrane, the chromosomes or the DNA at all times of culture. It was also able to induce lipid peroxidation and raise the levels of 8-OHdG and ROS in 6, 12 and 24 h. The results of the RT-PCR and the Western Blot indicated that DON is able to enhance mRNA or protein expressions of DNA repair genes and HO-1 in 6 h and to inhibit these expressions in 24 h. DON potentially triggers genotoxicity in human lymphocytes. This mechanism is probably related to depletion of antioxidase and oxidative damage to the DNA that reduced expression of HO-1, thereby inhibiting the ability of DNA repair.

  15. Silymarin and dimercaptosuccinic acid ameliorate lead-induced nephrotoxicity and genotoxicity in rats.

    PubMed

    Alcaraz-Contreras, Y; Mendoza-Lozano, R P; Martínez-Alcaraz, E R; Martínez-Alfaro, M; Gallegos-Corona, M A; Ramírez-Morales, M A; Vázquez-Guevara, M A

    2016-04-01

    We studied the effect of silymarin and dimercaptosuccinic acid (DMSA), a chelating agent that was administered individually or in combination against lead (Pb) toxicity in rats. Wistar rats (200 ± 20) were randomly divided into five groups. Group A served as a control. Groups B-E were exposed to 2000 ppm of lead acetate in drinking water for 8 weeks. Group B served as a positive control. Group C received silymarin (100 mg kg(-1) orally) for 8 weeks. Group D received DMSA (75 mg kg(-1) orally) once daily for the last 5 days of treatment. Group E received DMSA and silymarin as groups C and D, respectively. The effect of Pb was evaluated and accordingly the treatments on blood lead levels (BLLs), renal system, and genotoxic effects were calculated using comet assay. The BLLs were significantly increased following the exposition of lead acetate. The administration of silymarin and DMSA provided reduction in BLLs. Silymarin and DMSA provided significant protection on the genotoxic effect of Pb. The toxic effect of Pb on kidneys was also studied. Our data suggest that silymarin and DMSA improve the renal histopathological lesions.

  16. Cytotoxicity, oxidative stress and genotoxicity induced by glass fibers on human alveolar epithelial cell line A549.

    PubMed

    Rapisarda, Venerando; Loreto, Carla; Ledda, Caterina; Musumeci, Giuseppe; Bracci, Massimo; Santarelli, Lory; Renis, Marcella; Ferrante, Margherita; Cardile, Venera

    2015-04-01

    Man-made vitreous fibers have been widely used as insulation material as asbestos substitutes; however their morphology and composition raises concerns. In 1988 the International Agency for Research on Cancer classified fiberglass, rock wool, slag wool, and ceramic fibers as Group 2B, i.e. possibly carcinogenic to humans. In 2002 it reassigned fiberglass, rock and slag wool, and continuous glass filaments to Group 3, not classifiable as carcinogenic to humans. The aim of this study was to verify the cytotoxic and genotoxic effects and oxidative stress production induced by in vitro exposure of human alveolar epithelial cells A549 to glass fibers with a predominant diameter <3 μm (97%) and length >5 μm (93%). A549 cells were incubated with 5, 50, or 100 μg/ml (2.1, 21, and 42 μg/cm(2), respectively) of glass fibers for 72 h. Cytotoxicity and DNA damage were tested by the MTT and the Comet assay, respectively. Oxidative stress was determined by measuring inducible nitric oxide synthase (iNOS) expression by Western blotting, production of nitric oxide (NO) with Griess reagent, and concentration of reactive oxygen species by fluorescent quantitative analysis with 2',7'-dichlorofluorescein-diacetate (DCFH-DA). The results showed that glass fiber exposure significantly reduced cell viability and increased DNA damage and oxidative stress production in a concentration-dependent manner, demonstrating that glass fibers exert cytotoxic and genotoxic effects related to increased oxidative stress on the human alveolar cell line A549.

  17. Sam68/KHDRBS1 is critical for colon tumorigenesis by regulating genotoxic stress-induced NF-κB activation

    PubMed Central

    Fu, Kai; Sun, Xin; Wier, Eric M; Hodgson, Andrea; Liu, Yue; Sears, Cynthia L; Wan, Fengyi

    2016-01-01

    Nuclear factor kappa B (NF-κB)-mediated transcription is an important mediator for cellular responses to DNA damage. Genotoxic agents trigger a 'nuclear-to-cytoplasmic' NF-κB activation signaling pathway; however, the early nuclear signaling cascade linking DNA damage and NF-κB activation is poorly understood. Here we report that Src-associated-substrate-during-mitosis-of-68kDa/KH domain containing, RNA binding, signal transduction associated 1 (Sam68/KHDRBS1) is a key NF-κB regulator in genotoxic stress-initiated signaling pathway. Sam68 deficiency abolishes DNA damage-stimulated polymers of ADP-ribose (PAR) production and the PAR-dependent NF-κB transactivation of anti-apoptotic genes. Sam68 deleted cells are hypersensitive to genotoxicity caused by DNA damaging agents. Upregulated Sam68 coincides with elevated PAR production and NF-κB-mediated anti-apoptotic transcription in human and mouse colon cancer. Knockdown of Sam68 sensitizes human colon cancer cells to genotoxic stress-induced apoptosis and genetic deletion of Sam68 dampens colon tumor burden in mice. Together our data reveal a novel function of Sam68 in the genotoxic stress-initiated nuclear signaling, which is crucial for colon tumorigenesis. DOI: http://dx.doi.org/10.7554/eLife.15018.001 PMID:27458801

  18. Effects of iron oxide nanoparticles: cytotoxicity, genotoxicity, developmental toxicity, and neurotoxicity.

    PubMed

    Valdiglesias, Vanessa; Kiliç, Gözde; Costa, Carla; Fernández-Bertólez, Natalia; Pásaro, Eduardo; Teixeira, João Paulo; Laffon, Blanca

    2015-03-01

    Iron oxide nanoparticles (ION) with superparamagnetic properties hold great promise for use in various biomedical applications; specific examples include use as contrast agents for magnetic resonance imaging, in targeted drug delivery, and for induced hyperthermia cancer treatments. Increasing potential applications raise concerns over their potential effects on human health. Nevertheless, very little is currently known about the toxicity associated with exposure to these nanoparticles at different levels of biological organization. This article provides an overview of recent studies evaluating ION cytotoxicity, genotoxicity, developmental toxicity and neurotoxicity. Although the results of these studies are sometimes controversial, they generally indicate that surface coatings and particle size seem to be crucial for the observed ION-induced effects, as they are critical determinants of cellular responses and intensity of effects, and influence potential mechanisms of toxicity. The studies also suggest that some ION are safe for certain biomedical applications, while other uses need to be considered more carefully. Overall, the available studies provide insufficient evidence to fully assess the potential risks for human health related to ION exposure. Additional research in this area is required including studies on potential long-term effects. PMID:25209650

  19. Genotoxic effects of sodium arsenite and sodium arsenate after chronic exposure of Drosophila melanogaster larvae

    SciTech Connect

    Ramos-Morales, P.; Ordaz, M.G.; Munoz, A.

    1995-11-01

    Two arsenic compounds, namely: NaAsO{sub 2} (Sodium Arsenite) and Na{sub 2}HAsO{sub 4} (Sodium Arsenate) were tested for its chronic effect in somatic cells of Drosophila melanogaster. In a previous study in Drosophila we found that both compounds induced SLRL mutations, but failed to induce sex chromosome loss. In the SMART, after acute exposure, only sodium arsenite was positive when cells of the wings were used; however, both were positives in cells of the eyes of Drosophila. The genotoxicity of both compounds localized mainly on somatic cells, in agreement with reports on the carcinogenicity potential of arsenical compounds. The Somatic mutation and recombination test (SMART) was run employing cells of the wing imaginal discs from flr{sup 3}/mwh larvae. First instar larvae (24 {plus_minus} 4 h) were treated during 96 hours with sodium arsenite [0.015-4.0 ppm], and sodium arsenate [0.2-10 ppm], negative control was treated with distilled water. The frequency of spots by wing induced by the two arsenic salts were compared with control according with Frei and Wuergler procedure. Data show that sodium arsenite tested negative at all concentrations, but sodium arsenate tested positive at 0.8, 2 and 10 ppm (P<0.05). This results were consistent with the co-mutagenic role of sodium arsenite, but show that sodium arsenate was mutagenic in Drosophila test system under chronic exposure.

  20. Pirimicarb-based formulation-induced genotoxicity and cytotoxicity in the freshwater fish Cnesterodon decemmaculatus (Jenyns, 1842) (Pisces, Poeciliidae).

    PubMed

    Vera-Candioti, Josefina; Soloneski, Sonia; Larramendy, Marcelo L

    2015-11-01

    We analyzed the aspects of lethality, genotoxicity, and cytotoxicity in the ten spotted live-bearer exposed under laboratory conditions to the pirimicarb-based formulation Patton Flow® (50% active ingredient (a.i.)). Acute effects were evaluated using different end points for lethality, genotoxicity, and cytotoxicity. Median lethal concentration (LC50) estimation was employed as a bioassay for lethality, whereas micronucleus (MN) induction and alterations in erythrocyte/erythroblast frequency were used as end points for genotoxicity and cytotoxicity, respectively. Results demonstrated an LC5096h value of 88 mg/L. Patton Flow® increased the MN frequency in fish erythrocytes after 48 h of exposure at a concentration of 66 mg/L, whereas a concentration range of 22-66 mg/L was able to exert the same genotoxic effect at 96 h of treatment. Furthermore, cytotoxicity was also observed by alterations in erythrocyte/erythroblast frequencies within the concentration range of 22-66 mg/L, regardless of the exposure time. Our current observations provide evidence that Patton Flow® (50% a.i.) should be considered a clear lethal, cytotoxic, and genotoxic agent on Cnesterodon decemmaculatus. Thus, repeated applications of this carbamic insecticide can enter the aquatic environment and exert deleterious effects on aquatic organisms other than the evaluated species C. decemmaculatus.

  1. Subchronic mycotoxicoses in Wistar rats: assessment of the in vivo and in vitro genotoxicity induced by fumonisins and aflatoxin B(1), and oxidative stress biomarkers status.

    PubMed

    Theumer, M G; Cánepa, M C; López, A G; Mary, V S; Dambolena, J S; Rubinstein, H R

    2010-01-31

    Some evidence suggests that fumonisin B(1) (FB(1)), a worldwide toxic contaminant of grains produced by Fusarium verticillioides, exhibits an oxidative stress mediated genotoxicity. We studied the DNA damage (by the alkaline comet and the micronucleus tests) and biomarkers of cellular oxidative stress (malondialdehyde, MDA; catalase, CAT; and superoxide dismutase, SOD) in spleen mononuclear cells of male Wistar rats subchronically (90 days) fed on a control experimental diet (CED) or poisoned with experimental diets contaminated with a culture material containing 100 ppm of FB(1) (FED), with 40 ppb of aflatoxin B(1) (a common toxic co-contaminant in cereals, AFB(1)ED), and with a mixture of both toxins (MED). The DNA damage was found in 13.7%, 81.7%, 98.0% and 99.3% (comet assay) and in 2.8%, 7.0%, 10.8% and 8.8% (micronucleus technique) in groups CED, FED, AFB(1)ED and MED, respectively. The MDA levels as well as the CAT and SOD activities were increased in all the poisoned animals. A similar behavior was observed in cells exposed in vitro to the toxins. These data support the hypothesis of an oxidative stress mediated genotoxicity induced by FB(1). Furthermore, the extent of DNA damage assessed by the comet assay suggests a possible protective effect of the fumonisins-AFB(1) mixtures in vitro against the genotoxicity induced individually by the toxins.

  2. [Methylene blue as a supressor of the genotoxic effect of ultraviolet radiation with a wavelength of 300-400 nm].

    PubMed

    Chistiakov, V A; Sazykina, M A; Kolenko, M A; Cherviakov, G G; Usatov, A V

    2009-03-01

    Ultraviolet radiation with a wavelength of 300-400 nm is characteristic of sunlight at the earth surface and causes DNA damage mediated by energy transfer to O2 with the transformation of the latter in the singlet state. In connection with this, scavengers of reactive oxygen species (ROSs) are potential protectors against the genotoxic effect of this kind of radiation. It was found that the methylene blue dye at doses differing by several orders of magnitude from those that are toxic for humans is able to suppress completely the SOS response induced by UV with a wavelength of 300--400 nm in Escherichia coli.

  3. Emerging Disinfection Byproducts, Halobenzoquinones: Effects of Isomeric Structure and Halogen Substitution on Cytotoxicity, Formation of Reactive Oxygen Species, and Genotoxicity.

    PubMed

    Li, Jinhua; Moe, Birget; Vemula, Sai; Wang, Wei; Li, Xing-Fang

    2016-07-01

    Halobenzoquinones (HBQs) are a structurally diverse class of water disinfection byproducts. Here, we report a systematic study on the effects of isomeric structure and the type and number of halogen substitutions of HBQs on their cytotoxicity, formation of reactive oxygen species (ROS), and genotoxicity. Dynamic responses and IC50 histograms were obtained using real-time cell analysis, clearly ranking the cytotoxicity of the HBQs in Chinese hamster ovary (CHO-K1) cells. Strong isomeric structure effects were shown with 2,5-HBQ isomers inducing greater cytotoxicity than their corresponding 2,6-HBQ isomers (P < 0.05). HBQ-halogen substitution groups also influence cytotoxicity, as cytotoxicity increases across the dihalogenated HBQs: iodo- > bromo- > chloro-HBQs (P < 0.05). Determination of HBQ-induced ROS further supports isomeric structure and halogen substitution effects. HBQ-induced genotoxicity was shown as increased levels of 8-hydroxy-2'-deoxyguanosine and p53 protein. Pearson correlation analysis of the HBQ toxicity measurements with their physicochemical parameters demonstrates that dipole moment and the lowest unoccupied molecular orbital energy are two major structural influences on toxicity (r = -0.721 or -0.766, P < 0.05). Dipole moment also correlates with isomer toxicity. This study suggests that formation and occurrence of highly toxic iodo-HBQs and 2,5-HBQs warrant further investigation to fully assess the impact of HBQs in drinking water. PMID:26812484

  4. Apple juice attenuates genotoxicity and oxidative stress induced by cadmium exposure in multiple organs of rats.

    PubMed

    Gomes de Moura, Carolina Foot; Pidone Ribeiro, Flávia Andressa; Lucke, Gabriela; Boiago Gollucke, Andrea Pitelli; Fujiyama Oshima, Celina Tizuko; Ribeiro, Daniel Araki

    2015-10-01

    The aim of this study was to evaluate the health benefits associated with apple consumption following cadmium exposure. A total of 15 Wistar rats were distributed into three groups (n=5), as follows: control group (non-treated group, CTRL); cadmium group (Cd) and apple juice group (Cd+AJ). The results showed a decrease in the frequency micronucleated cells in bone marrow and hepatocytes in the group exposed to cadmium and treated with apple juice. Apple juice was also able to reduce the 8OHdG levels and to decrease genetic damage in liver and peripheral blood cells. Catalase (CAT) was decreased following apple juice intake. Taken together, our results demonstrate that apple juice seems to be able to prevent genotoxicity and oxidative stress induced by cadmium exposure in multiple organs of Wistar rats.

  5. Genotoxicity and antioxidant enzyme activity induced by hexavalent chromium in Cyprinus carpio after in vivo exposure.

    PubMed

    Kumar, Pavan; Kumar, Ravindra; Nagpure, Naresh S; Nautiyal, Prakash; Kushwaha, Basdeo; Dabas, Anurag

    2013-10-01

    Fish, being an important native of the aquatic ecosystem, are exposed to multipollution states and are therefore considered as model organisms for ecotoxicological studies of aquatic pollutants, including metal toxicity. We investigated oxidative stress (OS) in liver, kidney and gill tissues through antioxidant enzyme activities and genotoxicity induced in whole blood and gill tissues through comet assay and micronucleus (MN) test in Cyprinus carpio after 96-hour in vivo static exposure to potassium dichromate at three sublethal (SL) test concentrations, including SL-I [93.95 mg/L, i.e. one quarter of half-maximal lethal concentration (LC50)], SL-II (187.9 mg/L, i.e. one half of LC50), and SL-III (281.85 mg/L, i.e. three quarters of LC50), along with a control. The 96-hour LC50 value for potassium dichromate was estimated to be 375.8 mg/L in a static system in the test species. Tissues samples were collected at 24, 48, 72 and 96 hours postexposure. Results indicated that the exposed fish experienced OS as characterized by significant (p < 0.05) variation in antioxidant enzyme activities, as compared to the control. Activities of superoxide dismutase and glutathione peroxidase increased, whereas activity of catalase decreased with the progression of the experiment. The mean percent DNA damage in comet tail and MN induction in gills and whole blood showed a concentration-dependent increase up to 96-hour exposure. The findings of this study would be helpful in organ-specific risk assessment of Cr(VI)-induced OS and genotoxicity in fishes.

  6. Soil genotoxicity induced by successive applications of chlorothalonil under greenhouse conditions.

    PubMed

    Jin, Xiangxiang; Cui, Ning; Zhou, Wei; Khorram, Mahdi Safaei; Wang, Donghong; Yu, Yunlong

    2014-05-01

    Greenhouse production of vegetables has been developed rapidly in China. High temperature and humidity inside the greenhouse make this environment more suitable for fast reproduction of fungal diseases. Fungicides are among the chemicals used extensively in the greenhouse to prevent crops from invasive infections by phytopathogens; however, little is known about the accumulation of fungicides in soil and their effect on soil quality under greenhouse conditions. In the present study, the accumulation of the fungicide chlorothalonil (CT) and its toxic metabolite hydroxy-chlorothalonil (HCT) in soil as well as their related soil genotoxicity under greenhouse conditions was investigated. The results indicated that both CT and HCT accumulated in soil with repeated applications of CT, and the accumulation level was strongly correlated to application dosage and its frequency. In addition, soil genotoxicity, which was measured by Vicia faba, also increased with the accumulation of CT and HCT, and the main contributor to this phenomenon was CT rather than HCT. The data demonstrated that successive applications of fungicides may result in their accumulation in soil and thus a decline in soil quality.

  7. ACUTE DYSKERIN DEPLETION TRIGGERS CELLULAR SENESCENCE AND RENDERS OSTEOSARCOMA CELLS RESISTANT TO GENOTOXIC STRESS-INDUCED APOPTOSIS

    PubMed Central

    Lin, Ping; Mobasher, Maral E.; Alawi, Faizan

    2014-01-01

    Dyskerin is a conserved, nucleolar RNA-binding protein implicated in an increasing array of fundamental cellular processes. Germline mutation in the dyskerin gene (DKC1) is the cause of X-linked dyskeratosis congenita. Conversely, wild-type dyskerin is overexpressed in sporadic cancers, and high-levels may be associated with poor prognosis. It was previously reported that acute loss of dyskerin function via siRNA-mediated depletion slowed the proliferation of transformed cell lines. However, the mechanisms remained unclear. Using human U2OS osteosarcoma cells, we show that siRNA-mediated dyskerin depletion induced cellular senescence as evidenced by proliferative arrest, senescence-associated heterochromatinization and a senescence-associated molecular profile. Senescence can render cells resistant to apoptosis. Conversely, chromatin relaxation can reverse the repressive effects of senescence-associated heterochromatinization on apoptosis. To this end, genotoxic stress-induced apoptosis was suppressed in dyskerin-depleted cells. In contrast, agents that induce chromatin relaxation, including histone deacetylase inhibitors and the DNA intercalator chloroquine, sensitized dyskerin-depleted cells to apoptosis. Dyskerin is a core component of the telomerase complex and plays an important role in telomere homeostasis. Defective telomere maintenance resulting in premature senescence is thought to primarily underlie the pathogenesis of X-linked DC. Since U2OS cells are telomerase-negative, this leads us to conclude that loss of dyskerin function can also induce cellular senescence via mechanisms independent of telomere shortening. PMID:24690175

  8. Cytostatic and genotoxic effect of temephos in human lymphocytes and HepG2 cells.

    PubMed

    Benitez-Trinidad, A B; Herrera-Moreno, J F; Vázquez-Estrada, G; Verdín-Betancourt, F A; Sordo, M; Ostrosky-Wegman, P; Bernal-Hernández, Y Y; Medina-Díaz, I M; Barrón-Vivanco, B S; Robledo-Marenco, M L; Salazar, A M; Rojas-García, A E

    2015-06-01

    Temephos is an organophosphorus pesticide that is used in control campaigns against Aedes aegypti mosquitoes, which transmit dengue. In spite of the widespread use of temephos, few studies have examined its genotoxic potential. The aim of this study was to evaluate the cytotoxic, cytostatic and genotoxic effects of temephos in human lymphocytes and hepatoma cells (HepG2). The cytotoxicity was evaluated with simultaneous staining (FDA/EtBr). The cytostatic and genotoxic effects were evaluated using comet assays and the micronucleus technique. We found that temephos was not cytotoxic in either lymphocytes or HepG2 cells. Regarding the cytostatic effect in human lymphocytes, temephos (10 μM) caused a significant decrease in the percentage of binucleated cells and in the nuclear division index as well as an increase in the apoptotic cell frequency, which was not the case for HepG2 cells. The comet assay showed that temephos increased the DNA damage levels in human lymphocytes, but it did not increase the MN frequency. In contrast, in HepG2 cells, temephos increased the tail length, tail moment and MN frequency in HepG2 cells compared to control cells. In conclusion, temephos causes stable DNA damage in HepG2 cells but not in human lymphocytes. These findings suggest the importance of temephos biotransformation in its genotoxic effect.

  9. Cytostatic and genotoxic effect of temephos in human lymphocytes and HepG2 cells.

    PubMed

    Benitez-Trinidad, A B; Herrera-Moreno, J F; Vázquez-Estrada, G; Verdín-Betancourt, F A; Sordo, M; Ostrosky-Wegman, P; Bernal-Hernández, Y Y; Medina-Díaz, I M; Barrón-Vivanco, B S; Robledo-Marenco, M L; Salazar, A M; Rojas-García, A E

    2015-06-01

    Temephos is an organophosphorus pesticide that is used in control campaigns against Aedes aegypti mosquitoes, which transmit dengue. In spite of the widespread use of temephos, few studies have examined its genotoxic potential. The aim of this study was to evaluate the cytotoxic, cytostatic and genotoxic effects of temephos in human lymphocytes and hepatoma cells (HepG2). The cytotoxicity was evaluated with simultaneous staining (FDA/EtBr). The cytostatic and genotoxic effects were evaluated using comet assays and the micronucleus technique. We found that temephos was not cytotoxic in either lymphocytes or HepG2 cells. Regarding the cytostatic effect in human lymphocytes, temephos (10 μM) caused a significant decrease in the percentage of binucleated cells and in the nuclear division index as well as an increase in the apoptotic cell frequency, which was not the case for HepG2 cells. The comet assay showed that temephos increased the DNA damage levels in human lymphocytes, but it did not increase the MN frequency. In contrast, in HepG2 cells, temephos increased the tail length, tail moment and MN frequency in HepG2 cells compared to control cells. In conclusion, temephos causes stable DNA damage in HepG2 cells but not in human lymphocytes. These findings suggest the importance of temephos biotransformation in its genotoxic effect. PMID:25746384

  10. Evidence for the role of nitric oxide in antiapoptotic and genotoxic effect of nicotine on human gingival fibroblasts.

    PubMed

    Argentin, Gabriella; Cicchetti, Rosadele

    2006-11-01

    Resistance to apoptosis is essential for cancer survival and plays a critical role in carcinogenesis. Growing evidence suggests that nicotine can act as a tumor promoter, impairing apoptotic process in certain types of human cancer cell lines. Our previous study revealed in human gingival fibroblasts (HGFs) a concomitant antiapoptotic and genotoxic effect of nicotine, manifested by the attenuation of staurosporine (STP)-induced apoptosis and the increase of micronucleus frequency. The present report provides evidence that nitric oxide (NO) is critically involved in these actions. In vitro treatment with sodium nitroprusside as NO donor showed that NO produced similar effects as those observed with nicotine: it caused DNA damage and partially prevented apoptosis induced by staurosporine. Exposure of HGFs to nicotine, at concentrations similar to those found in the blood of habitual smokers, leads to the production of NO associated with the induction of inducible nitric oxide synthase (iNOS) expression. Experiments using an inhibitor of iNOS, N-monomethyl-L-arginine (NMA), together with nicotine confirmed the involvement of NO in the drug action, abrogating completely cell death and a good part of the genotoxicity. Finally, we show by different approaches that the inhibition of cell death by nicotine through NO release is related to modulation of caspase-1 activation. PMID:16927020

  11. Cyto-genotoxic and oxidative effects of a continuous UV-C treatment of liquid egg products.

    PubMed

    Mendes de Souza, Poliana; Briviba, Karlis; Müller, Alexandra; Fernández, Avelina; Stahl, Mario

    2013-06-01

    UV-C treatment of food is a promising non-thermal processing technology to improve food safety and preservation. Most of the chemical constituents of food absorb UV-C light that can lead to chemical modifications and quality changes. This work investigated the effects of UV-C treatment of liquid egg products on lipid, protein oxidations and potential cyto- and genotoxic effects on intestinal epithelial cells in vitro. Egg preparations (egg white, yolk, liquid whole egg) were treated with UV-C (254 nm, volumetric doses between 0 and 115,619 J L(-1)) using a commercial UV-C processing unit equipped with a Dean Flow reactor. UV-C treatment at high doses (from 32,181 J L(-1), about 2 times higher than that needed to inactivate 5 log of relevant microorganisms) showed an increased lipid oxidation in egg yolk and slight effects in liquid whole eggs; this was confirmed by slightly but not statistically significant increased peroxide values. UV-C induced also slight protein damage, characterised by the total sulfhydryl group reduction. These UV-C-induced oxidative modifications in egg preparations however did not cause any increase in the cyto- or genotoxic (DNA strand breaks) effects in intestinal Caco-2 cells.

  12. Sulforaphane inhibits CYP1A1 activity and promotes genotoxicity induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin in vitro

    SciTech Connect

    Yang, Fangxing; Zhuang, Shulin; Zhang, Chao; Dai, Heping; Liu, Weiping

    2013-06-15

    Increasing environmental pollution by carcinogens such as some of persistent organic pollutants (POPs) has prompted growing interest in searching for chemopreventive compounds which are readily obtainable. Sulforaphane (SFN) is isolated from cruciferous vegetables and has the potentials to reduce carcinogenesis through various pathways. In this study, we studied the effects of SFN on CYP1A1 activity and genotoxicity induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The results showed that SFN inhibited TCDD-induced CYP1A1 activity in H4IIE cells by directly inhibiting CYP1A1 activity, probably through binding to aryl hydrocarbon receptor and/or CYP1A1 revealed by molecular docking. However, SFN promoted TCDD-induced DNA damage in yeast cells and reduced the viability of initiated yeast cells. Besides, it is surprising that SFN also failed to reduce genotoxicity induced by other genotoxic reagents which possess different mechanisms to lead to DNA damage. Currently, it is difficult to predict whether SFN has the potentials to reduce the risk of TCDD based on the conflicting observations in the study. Therefore, further studies should be urgent to reveal the function and mechanism of SFN in the stress of such POPs on human health. - Highlights: • Sulforaphane inhibited TCDD-induced CYP1A1 activity in H4IIE cells. • Sulforaphane may bind to aryl hydrocarbon receptor and/or CYP1A1. • Sulforaphane promoted TCDD-induced DNA damage in yeast cells. • Sulforaphane may promote DNA damage by DNA strand breaks or DNA alkylation.

  13. Methotrexate-induced cytotoxicity and genotoxicity in germ cells of mice: intervention of folic and folinic acid.

    PubMed

    Padmanabhan, S; Tripathi, D N; Vikram, A; Ramarao, P; Jena, G B

    2009-02-19

    Methotrexate (MTX) is an anti-metabolite widely used in the treatment of neoplastic disorders, rheumatoid arthritis and psoriasis. The basis for its therapeutic efficacy is the inhibition of dihydrofolate reductase (DHFR), a key enzyme in the folic acid (FA) metabolism. FA is a water-soluble vitamin which is involved in the synthesis of purines and pyrimidines, the essential precursors of DNA. Folinic acid (FNA) is the reduced form of FA that circumvents the inhibition of DHFR. Folate supplementation during MTX therapy for psoriasis and inflammatory arthritis reduces both toxicity and side effects without compromising the efficacy. Further, FNA supplementation reduces the common side effects of MTX in the treatment of juvenile idiopathic arthritis. FA and FNA are reported to have protective effects on MTX-induced genotoxicity in the somatic cells; however their protective effects on the germ cells have not been much explored. Previously, we evaluated the cytotoxic and genotoxic effects of MTX in the germ cells of mice. In the present study, we have intervened FA and FNA for the protection of germ cell toxicity induced by MTX in male swiss mice. The animals were pre-treated with FA at the doses of 50, 100 and 200 microg/kg for 4 consecutive days per week and on day five; MTX was administered at the dose of 20mg/kg once. FNA was administered at the doses of 2.5, 5 and 10 mg/kg, 6 h (h) after single administration of MTX at the dose of 20 mg/kg. The dosing regimen was continued up to 10 weeks. The germ cell toxicity was evaluated using testes weight (wt), sperm count, sperm head morphology, sperm comet assay, histology, TUNEL and halo assay in testis. The results clearly demonstrate that prior administration of FA and post-treatment with FNA reduces the germ cell toxicity induced by MTX as evident from the decreased sperm head abnormalities, seminiferous tubule damage, sperm DNA damage, TUNEL positive cells and increased sperm counts. In the present study, we report

  14. Potential genotoxic effects of melted snow from an urban area revealed by the Allium cepa test.

    PubMed

    Blagojević, Jelena; Stamenković, Gorana; Vujosević, Mladen

    2009-09-01

    The presence of well-known atmospheric pollutants is regularly screened for in large towns but knowledge about the effects of mixtures of different pollutants and especially their genotoxic potential is largely missing. Since falling snow collects pollutants from the air, melted snow samples could be suitable for evaluating potential genotoxicity. For this purpose the Allium cepa anaphase-telophase test was used to analyse melted snow samples from Belgrade, the capital city of Serbia. Samples of snow were taken at two sites, characterized by differences in pollution intensity, in three successive years. At the more polluted site the analyses showed a very high degree of both toxicity and genotoxicity in the first year of the study corresponding to the effects of the known mutagen used as the positive control. At the other site the situation was much better but not without warning signals. The results showed that standard analyses for the presence of certain contaminants in the air do not give an accurate picture of the possible consequences of urban air pollution because the genotoxic potential remains hidden. The A. cepa test has been demonstrated to be very convenient for evaluation of air pollution through analyses of melted snow samples. PMID:19589556

  15. Evaluation of effects of melatonin and caffeic acid phenethyl ester on acute potassium dichromate toxicity and genotoxicity in rats

    PubMed Central

    Cengiz, Mujgan; Alansal, Nurnisa Oya; Tuncdemir, Matem; Tanriverdi, Gamze; Bayoglu, Burcu

    2016-01-01

    Objective: The aim of this study is to investigate the possible protective effects of melatonin and caffeic acid phenethyl ester (CAPE) on potassium dichromate (K2 Cr2O7)-induced nephrotoxicity and genotoxicity. Methods: A total of 40 Wistar albino rats were divided into five groups: control, K2Cr2O7(K2Cr2O715 mg/kg, one dose, i.p.), K2Cr2O7 + melatonin, K2Cr2O7 + CAPE, and K2Cr2O7 + melatonin + CAPE. Urine and blood samples were collected from rats before scarification. One kidney was collected for histopathological studies, and the other was stored at −80°C for further determination of catalase (CAT), superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), glutathione S-transferase (GST), and glutathione reductase (GR) levels with spectrophotometric method. Comet assay was used to evaluate the genotoxicity. Results: We observed a significant amelioration in genotoxicity by melatonin and simultaneous melatonin + CAPE treatment compared to K2Cr2O7 group (p1, p2< 0.05). SOD, CAT, GSH, GST, and MDA levels did not change when compared with controls. When K2Cr2O7 applied group was treated with melatonin and CAPE, neither melatonin nor CAPE made any changes in kidney GSH, GST, SOD, and MDA levels (P > 0.05). We noted that treatment with CAPE and melatonin + CAPE together caused a significant decrease in renal tissue damage, an upregulation in the kidney CAT levels (P < 0.05) and a slight healing at GR levels when compared with the K2Cr2O7 group. Conclusion: Our results revealed, CAPE and melatonin may have protective effects on K2Cr2O7 induced nephrotoxicity and cellular damage in rats. PMID:27756952

  16. Genotoxic effects of exposure to radiofrequency electromagnetic fields (RF-EMF) in HL-60 cells are not reproducible.

    PubMed

    Speit, Günter; Gminski, Richard; Tauber, Rudolf

    2013-08-15

    Conflicting results have been published regarding the induction of genotoxic effects by exposure to radiofrequency electromagnetic fields (RF-EMF). Various results indicating a genotoxic potential of RF-EMF were reported by the collaborative EU-funded REFLEX (Risk Evaluation of Potential Environmental Hazards From Low Energy Electromagnetic Field Exposure Using Sensitive in vitro Methods) project. There has been a long-lasting scientific debate about the reliability of the reported results and an attempt to reproduce parts of the results obtained with human fibroblasts failed. Another part of the REFLEX study was performed in Berlin with the human lymphoblastoid cell line HL-60; genotoxic effects of RF-EMF were measured by means of the comet assay and the micronucleus test. The plausibility and reliability of these results were also questioned. In order to contribute to a clarification of the biological significance of the reported findings, a repeat study was performed, involving scientists of the original study. Comet-assay experiments and micronucleus tests were performed under the same experimental conditions that had led to genotoxic effects in the REFLEX study. Here we report that the attempts to reproduce the induction of genotoxic effects by RF-EMF in HL-60 cells failed. No genotoxic effects of RF-EMF were measured in the repeat experiments. We could not find an explanation for the conflicting results. However, the negative repeat experiments suggest that the biological significance of genotoxic effects of RF-EMF reported by the REFLEX study should be re-assessed.

  17. Genotoxic effects of environmental estrogen-like compounds in CHO-K1 cells.

    PubMed

    Tayama, Sumiko; Nakagawa, Yoshio; Tayama, Kuniaki

    2008-01-01

    Some environmental estrogen-like compounds, such as bisphenol A (BPA), 4-nonylphenol (NP), 4-octylphenol (OP), propyl p-hydroxybenzoate (P-PHBA), and butyl p-hydroxybenzoate (B-PHBA), synthetic estrogen, diethylstilbestrol (DES), and natural estrogen, 17beta-estradiol (E2), were studied for their genotoxicity in CHO-K1 cells using sister-chromatid exchange (SCE), chromosome aberration (CA), and DNA strand break (comet) assays. Six of the chemicals, excluding E2, caused DNA migration in the comet assay and induced SCEs at one or more of the highest doses. Among the chemicals, OP produced an especially high incidence of SCEs. Structural CA was induced by five of the chemicals, excluding OP and NP, and BPA, E2, and DES also induced aneuploid cells. E2 and DES particularly increased the rate of polyploidy at high doses. The incidence of colchicine-mitosis-like (c-mitotic) figures suggesting spindle disrupting effects was also detected with five of the chemicals, excluding OP and NP, and six of the chemicals, excluding E2, caused endoreduplication (ERD), a form of nuclear polyploidization induced by block of cell cycle at G2 phase, at one or more high doses. Our present results suggest that OP and NP cause repairable DNA damage, including SCEs, and do not result in CA, while the damage caused by DES, BPA, P-PHBA, and B-PHBA results in the induction of CAs together with SCEs probably because of imperfect repair. We are unable to explain the observation that the DNA damage caused by E2 resulted in CA induction but not DNA migration or SCE induction, except for speculating that the DNA damage is different from that caused by DES and the estrogen-like chemicals. Our findings also suggest that E2, DES and BPA have aneuploidogenic properties, and that the former two of chemicals also are polyploidy-inducing agents. PMID:17913570

  18. Nicotine derived genotoxic effects in human primary parotid gland cells as assessed in vitro by comet assay, cytokinesis-block micronucleus test and chromosome aberrations test.

    PubMed

    Ginzkey, Christian; Steussloff, Gudrun; Koehler, Christian; Burghartz, Marc; Scherzed, Agmal; Hackenberg, Stephan; Hagen, Rudolf; Kleinsasser, Norbert H

    2014-08-01

    Genotoxic effects of nicotine were described in different human cells including salivary gland cells. Based on the high nicotine concentration in saliva of smokers or patients using therapeutic nicotine patches, the current study was performed to evaluate the genotoxic potential of nicotine in human salivary gland cells. Therefore, primary salivary gland cells from 10 patients undergoing parotid gland surgery were exposed to nicotine concentrations between 1 μM and 1000 μM for 1 h in the absence of exogenous metabolic activation. The acinar phenotype was proven by immunofluorescent staining of alpha-amylase. Genotoxic effects were evaluated using the Comet assay, the micronucleus test and the chromosome aberration test. Cytotoxicity and apoptosis were determined by trypan blue exclusion test and Caspase-3 assay. Nicotine was able to induce genotoxic effects in all three assays. The chromosome aberration test was the most sensitive and increases in numerical and structural (chromatid-type and chromosome-type) aberrations were seen at ≥1 μM, whereas increases in micronuclei frequency were detected at 10 μM and DNA damage as measured in the Comet assay was noted at >100 μM. No cytotoxic damage or influence of apoptosis could be demonstrated. Nicotine as a possible risk factor for tumor initiation in salivary glands is still discussed controversially. Our results demonstrated the potential of nicotine to induce genotoxic effects in salivary gland cells. These results were observed at saliva nicotine levels similar to those found after oral or transdermal exposure to nicotine and suggest the necessity of careful monitoring of the use of nicotine in humans. PMID:24698733

  19. Evaluation of cytotoxic and genotoxic effects of Benodanil by using Allium and Micronucleus assays.

    PubMed

    Akyıl, Dilek; Özkara, Arzu; Erdoğmuş, S Feyza; Eren, Yasin; Konuk, Muhsin; Sağlam, Esra

    2016-01-01

    The aim of this study was to evaluate the potential cytotoxic effects of Benodanil fungicide by employing both mitotic index (MI) and mitotic phases on the root meristem cells of Allium cepa and genotoxic effects by using in vitro micronucleus assay (MN) in human peripheral blood lymphocyte. In the Allium root growth inhibition test, the EC50 value was first determined as 25 ppm. Then, 2 × EC50 value (50 ppm), EC50 value (25 ppm), and 1/2 × EC50 value (12.5 ppm) were tested with different treatment periods (24, 48, and 72 h). Both negative and positive controls were also used in parallel experiments. We obtained that mitotic index and prophase index decreased when compared with the control in all concentrations. In the micronucleus assay, lymphocytes were treated with various concentrations (250, 500, 750, and 1000 µg/ml) of Benodanil for 24 and 48 h. The results showed that Benodanil did not induce MN frequency in all concentrations of both treatment periods. Additionally, it was determined that this pesticide decreased nuclear division index (NDI) significantly. It was concluded that Benodanil has a cytotoxic effects depending on decreasing of MI and NDI. PMID:26333298

  20. The cytotoxic and genotoxic effects of metalaxy-M on earthworms (Eisenia fetida).

    PubMed

    Liu, Tong; Zhu, Lusheng; Han, Yingnan; Wang, Jinhua; Wang, Jun; Zhao, Yan

    2014-10-01

    As the main optical isomer of metalaxyl, metalaxyl-M has been widely used worldwide in recent years because of its notable effect on the prevention and control of crop diseases. Together with the toxicity and degradation of metalaxyl-M, the chemical has attracted the attention of researchers. The present study examined the toxic effects of metalaxyl-M on earthworms at 0 mg kg(-1) , 0.1 mg kg(-1) , 1 mg kg(-1) , and 3 mg kg(-1) on days 7, 14, 21 and 28 after exposure. The results showed that metalaxyl-M could cause an obvious increase in the production of reactive oxygen species (ROS) when the concentration was higher than 0.1 mg kg(-1) , which led to lipid peroxidation in earthworms. Metalaxyl-M can induce DNA damage in earthworms, and the level of DNA damage markedly increased with increasing the concentration of metalaxyl-M. Metalaxyl-M also has a serious influence on the activities of antioxidant enzymes, which results in irreversible oxidative damage in cells. The changes of these indicators all indicated that metalaxyl-M may cause cytotoxic and genotoxic effects on earthworms.

  1. BisGMA-induced cytotoxicity and genotoxicity in macrophages are attenuated by wogonin via reduction of intrinsic caspase pathway activation.

    PubMed

    Huang, Fu-Mei; Chang, Yu-Chao; Lee, Shiuan-Shinn; Yeh, Chung-Hsin; Lee, Kevin Gee; Huang, Yi-Chun; Chen, Chun-Jung; Chen, Wen-Ying; Pan, Pin-Ho; Kuan, Yu-Hsiang

    2016-02-01

    Bisphenol-A-glycidyldimethacrylate (BisGMA) is a frequently used monomer in dental restorative resins. However, BisGMA could leach from dental restorative resins after polymerization leading to inflammation in the peripheral environment. Wogonin, a natural flavone derivative, has several benefits, such as antioxidative, anti-inflammatory and neuroprotective properties. Pretreatment of macrophage RAW264.7 cells with wogonin inhibited cytotoxicity which is induced by BisGMA in a concentration-dependent manner. BisGMA induced apoptotic responses, such as redistribution of phosphatidylserine from the internal to the external membrane and DNA fragmentation, were decreased by wogonin in a concentration-dependent manner. In addition, BisGMA-induced genotoxicity, which detected by cytokinesis-blocked micronucleus and single-cell gel electrophoresis assays, were inhibited by wogonin in a concentration-dependent manner. Furthermore, wogonin suppressed BisGMA-induced activation of intrinsic caspase pathways, such as caspases-3 and -8. Parallel trends were observed in inhibition of caspase-3 and -8 activities, apoptosis, and genotoxicity. These results indicate wogonin suppressed the BisGMA-induced apoptosis and genotoxicity mainly via intrinsic caspase pathway in macrophages. PMID:26756871

  2. Genotoxicity effect of nitrobenzene on soybean (Glycine max) root tip cells.

    PubMed

    Guo, Donglin; Ma, Jun; Li, Rui; Guo, Changhong

    2010-06-15

    Nitrobenzene is a synthetic compound widely used in industry which can lead to environmental pollution. While the toxicity and carcinogenicity of nitrobenzene on humans and animals have been studied, less is known about its genotoxicity to plants. In this study, the genotoxic effects of nitrobenzene were investigated with growing soybean seedlings in solution culture. Compared with the control, the growth of soybean seedlings (taproot length, longest lateral root length and lateral roots number) decreased and showed statistics difference at nitrobenzene test concentration of 50 and 100mg/L. Micronucleus, chromosomal bridge and others chromosomal aberrations were observed in soybean root tip cells exposed to nitrobenzene. Frequency of chromosomal aberrations increased linearly with nitrobenzene test concentration between 5 and 50mg/L and decreased at 100mg/L which showed significant difference between control and 25mg/L or higher test concentration. Results of the present study suggest that nitrobenzene has genotoxicity on soybean root tip cells. The mechanism of genotoxicity of NB needs further study. It is concluded that high environmental levels of nitrobenzene in rivers, lakes and dam waters are hazardous to aquatic species and to irrigated plants.

  3. Genotoxic and cytostatic effects of 6-pentadecyl salicylic anacardic acid in transformed cell lines and peripheral blood mononuclear cells.

    PubMed

    Alam-Escamilla, David; Estrada-Muñiz, Elizabet; Solís-Villegas, Erik; Elizondo, Guillermo; Vega, Libia

    2015-01-01

    In Mexico, as in many other countries, traditional medicine is used for the treatment of several diseases. In particular, Amphipterygium adstringens infusion is used for gastritis, gastric ulcers, and gastric cancer. Extracts from this tree have microbicidal effects against Helicobacter pylori, an important risk factor for gastric cancer development. Anacardic acids are constituents of A. adstringens, and 6-pentadecyl salicylic acid (6-PSA) is the most abundant. However, there is a lack of information regarding the effects of 6-PSA on cancer cells. Therefore, we investigated whether 6-PSA has differential effects on the induction of genotoxicity, cytostaticity, and apoptosis in normal human peripheral blood mononucleated cells (PBMCs), bone marrow polychromatic erythrocytes of Balb/c mice, and human transformed cell lines derived from both gastric cancer (AGS cells) and leukaemia (K562 cells). Treatment with 6-PSA (30-150 μM) reduced the viability of AGS and K562 cells together with a moderate, but significant, increase in the frequency of micronucleated cells and the induction of DNA breakage (Comet Assay). Moreover, 6-PSA increased the apoptosis rate in both the AGS and K562 cell lines in a caspase 8-dependent manner. In contrast, neither cytotoxicity nor genotoxicity were observed in PBMCs or bone marrow polychromatic erythrocytes of Balb/c mice after treatment with low doses of 6-PSA (0.2-2.0 mg/Kg). Instead, 6-PSA treatment resulted in the inhibition of PBMC proliferation, which was reversible after the compound was removed. Additionally, 6-PSA treatments (2-20 mg/Kg) increased the frequency of mature polychromatic erythrocytes in the bone marrow, suggesting a possible effect on the differentiation process of immune cells. The present results indicate that 6-PSA induces cytotoxicity and moderate genotoxicity, together with an increase in the apoptosis rate, in a caspase 8-dependent manner in gastric cancer cells. In contrast, a low toxicity was observed when

  4. Protective effect of lactofermented beetroot juice against aberrant crypt foci formation and genotoxicity of fecal water in rats.

    PubMed

    Klewicka, Elżbieta; Nowak, Adriana; Zduńczyk, Zenon; Cukrowska, Bożena; Błasiak, Janusz

    2012-09-01

    The aim of the study was to investigate the effects of beetroot juice fermented by Lactobacillus brevis 0944 and Lactobacillus paracasei 0920 (FBJ) on carcinogen induction of aberrant crypt foci (ACF) in rat colon. N-Nitroso-N-methylurea (MNU) was used as carcinogen, which was administrated intragastrically at a dose of 50 mg/kg on the 23rd and 26th day of the experiment. Additionally, we investigated the cytotoxicity and genotoxicity of fecal water from experimental animals in the Caco 2 cell line, evaluated by MTT/NRU tests and the comet assay, respectively, as well as by the count of bacteria adhered to colon epithelium assessed by fluorescence in situ hybridization and DAPI staining. The experimental rats were divided into four groups based on diet type: basal diet, basal diet supplemented with FBJ, basal diet and MNU treatment, and basal diet supplemented with FBJ and MNU treatment. FBJ significantly reduced the number of ACF in MNU-treated rats (from 55±18 to 21±6). Moreover, the number of extensive aberrations (more than 4 crypts in a focus) decreased from 45±21 to 7±4. Fecal water obtained from rats fed with an MNU-containing diet induced pronounced cytotoxic and genotoxic effects in Caco 2 cells, but FBJ supplementation of the diet abolished these effects. The presence of FBJ in the diet significantly increased the count of bacteria, including Lactobacillus/Enterococcus, adhered to colonic epithelium. In conclusion, supplementation of the diet with lactofermented beetroot juice may provide protection against precancerous aberrant crypt formation and reduce the cytotoxic and genotoxic effects of fecal water. PMID:21185162

  5. Evaluation of titanium dioxide nanocrystal-induced genotoxicity by the cytokinesis-block micronucleus assay and the Drosophila wing spot test.

    PubMed

    Reis, Érica de Melo; Rezende, Alexandre Azenha Alves de; Oliveira, Pollyanna Francielli de; Nicolella, Heloiza Diniz; Tavares, Denise Crispim; Silva, Anielle Christine Almeida; Dantas, Noelio Oliveira; Spanó, Mário Antônio

    2016-10-01

    Titanium dioxide nanocrystals (TiO2 NCs) crystalline structures include anatase, rutile and brookite. This study evaluated the genotoxic effects of 3.4 and 6.2 nm anatase TiO2 NCs and 78.0 nm predominantly rutile TiO2 NCs through an in vitro micronucleus (MN) assay using V79 cells and an in vivo somatic mutation and recombination test in Drosophila wings. The MN assay was performed with nontoxic concentrations of TiO2 NCs. Only anatase (3.4 nm) at the highest concentration (120 μM) induced genotoxicity in V79 cells. In the in vivo test, Drosophila melanogaster larvae obtained from standard (ST) or high bioactivation (HB) crosses were treated with TiO2 NCs. In the ST cross, no mutagenic effects were observed. However, in the HB cross, TiO2 NCs (3.4 nm) were mutagenic at 1.5625 and 3.125 mM, while 78.0 nm NCs increased mutant spots at all concentrations tested except 3.125 mM. Only the smallest anatase TiO2 NCs induced mutagenic effects in vitro and in vivo. For rutile TiO2 NCs, no clastogenic/aneugenic effects were observed in the MN assay. However, they were mutagenic in Drosophila. Therefore, both anatase and rutile TiO2 NCs induced mutagenicity. Further research is necessary to clarify the TiO2 NCs genotoxic/mutagenic action mechanisms.

  6. Evaluation of titanium dioxide nanocrystal-induced genotoxicity by the cytokinesis-block micronucleus assay and the Drosophila wing spot test.

    PubMed

    Reis, Érica de Melo; Rezende, Alexandre Azenha Alves de; Oliveira, Pollyanna Francielli de; Nicolella, Heloiza Diniz; Tavares, Denise Crispim; Silva, Anielle Christine Almeida; Dantas, Noelio Oliveira; Spanó, Mário Antônio

    2016-10-01

    Titanium dioxide nanocrystals (TiO2 NCs) crystalline structures include anatase, rutile and brookite. This study evaluated the genotoxic effects of 3.4 and 6.2 nm anatase TiO2 NCs and 78.0 nm predominantly rutile TiO2 NCs through an in vitro micronucleus (MN) assay using V79 cells and an in vivo somatic mutation and recombination test in Drosophila wings. The MN assay was performed with nontoxic concentrations of TiO2 NCs. Only anatase (3.4 nm) at the highest concentration (120 μM) induced genotoxicity in V79 cells. In the in vivo test, Drosophila melanogaster larvae obtained from standard (ST) or high bioactivation (HB) crosses were treated with TiO2 NCs. In the ST cross, no mutagenic effects were observed. However, in the HB cross, TiO2 NCs (3.4 nm) were mutagenic at 1.5625 and 3.125 mM, while 78.0 nm NCs increased mutant spots at all concentrations tested except 3.125 mM. Only the smallest anatase TiO2 NCs induced mutagenic effects in vitro and in vivo. For rutile TiO2 NCs, no clastogenic/aneugenic effects were observed in the MN assay. However, they were mutagenic in Drosophila. Therefore, both anatase and rutile TiO2 NCs induced mutagenicity. Further research is necessary to clarify the TiO2 NCs genotoxic/mutagenic action mechanisms. PMID:27562929

  7. SB202190 affects cell response to hydroxyurea-induced genotoxic stress in root meristems of Vicia faba.

    PubMed

    Winnicki, Konrad; Maszewski, Janusz

    2012-11-01

    Genotoxic stress caused by a variety of chemical and physical agents may lead to DNA breaks and genome instability. Response to DNA damage depends on ATM/ATR sensor kinases and their downstream proteins, which arrange cell cycle checkpoints. Activation of ATM (ataxia-telangiectasia-mutated)/ATR (ATM and Rad 3-related) signaling pathway triggers cell cycle arrest (by keeping cyclin-Cdk complexes inactive), combined with gamma-phosphorylation of histone H2A.X and induction of DNA repair processes. However, genotoxic stress activates also mitogen-activated protein kinases (MAPKs) which may control the functions of checkpoint proteins both directly, by post-translational modifications, or indirectly, by regulation of their expression. Our results indicate that in root meristem cells of Vicia faba, MAP kinase signaling pathway takes part in response to hydroxyurea-induced genotoxic stress. It is shown that SB202190, an inhibitor of p38 MAP kinase, triggers PCC (premature chromosome condensation) more rapidly, but only if cell cycle checkpoints are alleviated by caffeine. Since SB202190 and, independently, caffeine reduces HU-mediated histone H4 Lys5 acetylation, it may be that there is a cooperation of MAP kinase signaling pathways and ATM/ATR-dependent checkpoints during response to genotoxic stress.

  8. Genotoxic effects of 8-hydroxylquinoline in loach (Misgurnus anguillicaudatus) assessed by the micronucleus test, comet assay and RAPD analysis.

    PubMed

    Nan, Ping; Xia, Xiao-hua; Du, Qi-yan; Chen, Jian-jun; Wu, Xiao-hua; Chang, Zhong-jie

    2013-05-01

    This study was a preliminary step in evaluating the genotoxic effects of 8-hydroxylquinoline (8-HOQ) in loach (Misgurnus anguillicaudatus) using the micronucleus, comet and RAPD assays. In the micronucleus test and comet assay, the micronuclei rate (%) and three comet parameters (trailing rate, tail length and tail moment) in treated fish increased with increasing 8-HOQ concentration and treatment time. These results showed that exposure to 8-HOQ significantly induced genetic toxicity in loach blood cells. A subsequent RAPD assay also showed that 8-HOQ induced a genotoxic effect in loach. Among the 23 tested RAPD primers, 11 primers produced unique polymorphic band patterns and generated RAPD profile variations that displayed the band intensity, disappearance of bands and appearance of new bands of amplified DNA in the 8-HOQ-treated genomic DNA samples. In addition, the variation in RAPD profiles was time- and concentration-dependent. These results suggested that 8-HOQ is potentially harmful to fish and may be a toxic contaminant in the aquatic environment.

  9. Anemia and genotoxicity induced by sub-chronic intragastric treatment of rats with titanium dioxide nanoparticles.

    PubMed

    Grissa, Intissar; Elghoul, Jaber; Ezzi, Lobna; Chakroun, Sana; Kerkeni, Emna; Hassine, Mohsen; El Mir, Lassaad; Mehdi, Meriem; Ben Cheikh, Hassen; Haouas, Zohra

    2015-12-01

    Titanium dioxide nanoparticles (TiO2 NPs) are widely used for their whiteness and opacity. We investigated the hematological effects and genotoxicity of anatase TiO2 NPs following sub-chronic oral gavage treatment. TiO2-NPs were characterized by X-ray diffractometry (XRD), X-ray photoelectron spectroscopy (XPS), and transmission electron microscopy (TEM). Wistar rats were treated with anatase TiO2 NPs by intragastric administration for 60 days. Hematological analysis showed a significant decrease in RBC and HCT and a significant increase in MCV, PLT, MPV and WBC at higher doses. Furthermore, abnormally shaped red cells, sometimes containing micronuclei, and hyper-segmented neutrophil nuclei were observed with TiO2 NPs treatment. The micronucleus test revealed damage to chromosomes in rat bone marrow at 100 and 200mg/kg bw; the comet assay showed significant DNA damage at the same doses.

  10. In vitro genoprotective and genotoxic effect of nicotine on human leukocytes evaluated by the comet assay.

    PubMed

    Sobkowiak, Robert; Musidlak, Jakub; Lesicki, Andrzej

    2014-07-01

    The comet assay was used to measure the DNA damage induced in vitro by nicotine in human leukocytes as the extent of DNA migration in the comet head area, tail length, percent DNA in the tail, and Olive tail moment. Samples of whole blood were collected and blood cells were challenged with acute doses of 0.1, 1 and 10 µM of (-)-nicotine for 60 minutes. We found that nicotine treatment had dose-dependent effects on the level of DNA damage. At 1 and 10 µM of nicotine, both Olive tail moment and percent DNA in the tail significantly increased (p < 0.001), compared to the control. In the presence of 10 µM of nicotine, the shortest tail length and the smallest head area were detected. At a concentration of 0.1 µM, surprisingly, DNA damage detected by the comet assay was lower than in the control, which was proved by the observed significantly (p < 0.001) lower Olive tail moment and percent DNA in the tail as well as larger head area. The results suggest that nicotine, at a reasonably low concentration (0.1 µM), comparable to those found in the blood of habitual smokers, may have a protective effect, whereas higher doses of nicotine (1 and 10 µM) are genotoxic. The possible participation of reactive oxygen species in the DNA-damaging potential of nicotine is discussed. PMID:24245828

  11. Genotoxic effect of Bothrops snake venoms and isolated toxins on human lymphocyte DNA.

    PubMed

    Marcussi, Silvana; Stábeli, Rodrigo G; Santos-Filho, Norival A; Menaldo, Danilo L; Silva Pereira, Luciana L; Zuliani, Juliana P; Calderon, Leonardo A; da Silva, Saulo L; Antunes, Lusânia M Greggi; Soares, Andreimar M

    2013-04-01

    In the present study, micronucleus with cytokinesis blocking and comet assays were used to evaluate the genotoxic potential of Bothrops jararacussu, Bothrops atrox, Bothrops moojeni, Bothrops alternatus (Rhinocerophis alternatus) and Bothrops brazili snake venoms, and also of some isolated toxins (MjTX-I, BthTX-I and II myotoxins, BjussuMP-II metalloprotease, and BatxLAAO l-amino acid oxidase) on human lymphocytes. Significant DNA damages were observed, indicating genotoxic potential after exposure of the lymphocytes to the toxins BthTX-I, II and BatxLAAO compared to untreated and Cisplatin-treated controls, which were able to induce greater formation of micronuclei. B. brazili, B. jararacussu and B. atrox crude venoms also presented genotoxic potential, and the latter two induced DNA breakage 5 times more often than in normal environmental conditions (control without treatment). B. jararacussu venom and its isolated toxins, as well as an LAAO from B. atrox, were able to cause lymphocyte DNA breakage in the comet test with more than 85% damage levels. The DNA damage evaluation allows a widening of the toxic-pharmacological characterization of snake venoms and their toxins and also contributes to the understanding of the mechanisms of action of these molecules in several human pathologies. PMID:23333649

  12. Evaluation of genotoxicity and pro-oxidant effect of the azo dyes: acids yellow 17, violet 7 and orange 52, and of their degradation products by Pseudomonas putida mt-2.

    PubMed

    Ben Mansour, Hedi; Corroler, David; Barillier, Daniel; Ghedira, Kamel; Chekir, Leila; Mosrati, Ridha

    2007-09-01

    Acids yellow 17, violet 7 and orange 52, very important commercial azo dyes used in the textile, food, paper and cosmetic industries, were degraded by Pseudomonas putida mt-2 at concentrations up to 100mg/l. The culture media was completely decolorized under static incubation for 60 h, this faster than under continuous shaking incubation. SOS chromotest using Escherichia coli PQ37, with and without metabolic activation (S-9 preparations), was used to assess genotoxicity potential of these dyes before and after biodegradation. None of these dyes or their metabolites was found to be genotoxic in the absence of "Araclor-Induced rat liver microsome" preparations (S-9). However, in presence of the preparation S-9, the genotoxicity of the biodegradation products was highlighted. Metabolites resulting from static cultures were more genotoxic than those obtained in shaken conditions. In addition to genotoxic effects, metabolites have shown a significant ability to induce the formation of superoxide free radical anion (O(2)(*-)). The toxicities generated by the pure azo dyes and the pure azo-reduction products (sulfanilic acid, N,N'-dimethyl-p-phenylenediamine and 4'-aminoacetanilid) were compared. These results suggest that P. putida mt-2 degrades the studied azo dyes in two steps: an azo-reduction followed by an oxygen-dependent metabolization. Some of the derived metabolites would be responsible of genotoxicity and metabolic toxicity.

  13. In-Vitro Carbofuran Induced Genotoxicity in Human Lymphocytes and Its Mitigation by Vitamins C and E

    PubMed Central

    Sharma, Ratnesh Kumar; Sharma, Bechan

    2012-01-01

    Various efforts have been made in past in order to predict the underlying mechanism of pesticide-induced toxicity using in vitro and animal models, however, these predictions may or may not be directly correlated with humans. The present study was designed to investigate the carbofuran induced genotoxicity and its amelioration by vitamins C and E by treating human peripheral blood lymphocytes (PBLs) with different concentrations (0, 0.5, 1.25, 2.5, 3.75 and 5.0 μM) of this compound. The treatment of PBLs with carbofuran displayed significant DNA damage in concentration dependent manner. The carbofuran induced genotoxicity could be ameliorated to considerable extent by pretreatment of PBLs with equimolar (10 μM) concentration of each of the vitamins C and E; the magnitude of protection by vitamin E being higher than by vitamin C. Also, it was found that the level of protection by these vitamins was higher when PBLs were treated with lower concentrations of pesticide. The significant DNA damage as observed by H2O2, a positive control in the present study, and its amelioration by natural antioxidants (vitamins C and E) lend an evidence to suggest that carbofuran would have caused genotoxicity via pesticide induced oxidative stress. PMID:22377731

  14. In-vitro carbofuran induced genotoxicity in human lymphocytes and its mitigation by vitamins C and E.

    PubMed

    Sharma, Ratnesh Kumar; Sharma, Bechan

    2012-01-01

    Various efforts have been made in past in order to predict the underlying mechanism of pesticide-induced toxicity using in vitro and animal models, however, these predictions may or may not be directly correlated with humans. The present study was designed to investigate the carbofuran induced genotoxicity and its amelioration by vitamins C and E by treating human peripheral blood lymphocytes (PBLs) with different concentrations (0, 0.5, 1.25, 2.5, 3.75 and 5.0 μM) of this compound. The treatment of PBLs with carbofuran displayed significant DNA damage in concentration dependent manner. The carbofuran induced genotoxicity could be ameliorated to considerable extent by pretreatment of PBLs with equimolar (10 μM) concentration of each of the vitamins C and E; the magnitude of protection by vitamin E being higher than by vitamin C. Also, it was found that the level of protection by these vitamins was higher when PBLs were treated with lower concentrations of pesticide. The significant DNA damage as observed by H_{2}O_{2}, a positive control in the present study, and its amelioration by natural antioxidants (vitamins C and E) lend an evidence to suggest that carbofuran would have caused genotoxicity via pesticide induced oxidative stress.

  15. Pluchea lanceolata attenuates cadmium chloride induced oxidative stress and genotoxicity in Swiss albino mice.

    PubMed

    Jahangir, Tamanna; Khan, Tajdar Husain; Prasad, Lakshmi; Sultana, Sarwat

    2005-09-01

    Cadmium intoxication induces lipid peroxidation and causes oxidative damage to various tissues by altering antioxidant defence system enzymes. At 24 h after treatment with a single intraperitoneal dose of cadmium chloride (5 mg kg-1), Swiss albino mice showed a significant increase in the levels of malanodialdehyde and xanthine oxidase (P<0.001), and a concomitant depletion of renal glutathione, catalase (P<0.001) and other antioxidant enzymes. CdCl2 also led to a simultaneous increase in micronuclei formation (P<0.001) and chromosomal aberrations (P<0.05) in mouse bone marrow cells. Oral pre-treatment with Pluchea lanceolata extract at doses of 100 and 200 mg kg-1 for 7 consecutive days before CdCl2 intoxication caused a significant reduction in malanodialdehyde formation and xanthine oxidase activity (P<0.001). A significant restoration of the activity of antioxidant defence system enzymes such as catalase, glutathione peroxidase (P<0.05), glutathione-S-transferase and glutathione reductase (P<0.001) was observed. A significant dose-dependent decrease in chromosomal aberrations and micronuclei formation was also observed (P<0.05). The results indicate that pre-treatment with P. lanceolata attenuates cadmium chloride induced oxidative stress and genotoxicity by altering antioxidant enzymes and reducing chromatid breaks and micronuclei formation. PMID:16105241

  16. Assessment of in vitro genotoxic and cytotoxic effects of flurbiprofen on human cultured lymphocytes.

    PubMed

    Timocin, Taygun; Ila, Hasan Basri; Dordu, Tuba; Husunet, Mehmet Tahir; Tazehkand, Mostafa Norizadeh; Valipour, Ebrahim; Topaktas, Mehmet

    2016-01-01

    Flurbiprofen is non-steroidal anti-inflammatory drug which is commonly used for its analgesic, antipyretic, and anti-inflammatory effects. The purpose of the study was to explore the genotoxic and cytotoxic effects of flurbiprofen in human cultured lymphocytes by sister chromatid exchange, chromosome aberration, and cytokinesis-blocked micronucleus tests. 10, 20, 30, and 40 μg/mL concentrations of flurbiprofen (solvent is DMSO) were used to treatment of human cultured lymphocytes at two different treatment periods (24 and 48 h). Flurbiprofen had no significant genotoxic effect in any of these tests. But exposing to flurbiprofen for 24 and 48 h led to significant decrease on proliferation index, mitotic index, and nuclear division index (NDI). Also, all decreases were concentration-dependent (except NDI at 24 h treatment period). Consequently, the findings of this research showed that flurbiprofen had cytotoxic effects in human blood lymphocytes.

  17. Determination of genotoxic effects of Imazethapyr herbicide in Allium cepa root cells by mitotic activity, chromosome aberration, and comet assay.

    PubMed

    Liman, Recep; Ciğerci, İbrahim Hakkı; Öztürk, Nur Serap

    2015-02-01

    Imazethapyr (IM) is an imidazolinone herbicide that is currently used for broad-spectrum weed control in soybean and other legume crops. In this study, cytotoxic and genotoxic effects of IM were investigated by using mitotic index (MI), mitotic phases, chromosomal abnormalities (CAs) and DNA damage on the root meristem cells of Allium cepa. In Allium root growth inhibition test, EC50 value was determined as 20 ppm, and 0.5xEC50, EC50 and 2xEC50 concentrations of IM herbicide were introduced to onion tuber roots. Distilled water and methyl methane sulfonate (MMS, 10 mg/L) were used as a negative and positive control, respectively. As A. cepa cell cycle is 24 hours, so, application process was carried out for 24, 48, 72 and 96 hours. All the applied doses decreased MIs compared to control group and these declines were found to be statistically meaningful. Analysis of the chromosomes showed that 10 ppm IM except for 48 h induced CAs but 40 ppm IM except for 72 h decreased CAs. DNA damage was found significantly higher in 20 and 40 ppm of IM compared to the control in comet assay. These results indicated that IM herbicide exhibits cytotoxic activity but not genotoxic activity (except 10 ppm) and induced DNA damage in a dose dependent manner in A. cepa root meristematic cells. PMID:25752428

  18. Cytotoxic and genotoxic effects of high concentrations of the immunosuppressive drugs cyclosporine and tacrolimus in MRC-5 cells.

    PubMed

    Cilião, H L; Ribeiro, D L; Camargo-Godoy, R B O; Specian, A F L; Serpeloni, J M; Cólus, I M S

    2015-02-01

    Immunosuppressive drugs are used to suppress immune system activity in transplant patients and reduce the risk of organ rejection. The present study evaluated the potential cytotoxic, genotoxic and mutagenic of the immunosuppressive drugs cyclosporine (CsA) and tacrolimus (FK-506) on normal human fibroblasts (MRC-5 cells). Based on plasma concentrations of the immunosuppressive drugs, which were obtained from the records of kidney transplant patients at the Kidney Institute of Londrina, Brazil, 11 concentrations of each immunosuppressive were chosen to evaluate cell viability using the MTT assay. From these results, CsA and FK-506 concentrations of 135, 300, 675, and 1520 ng/ml and 8, 16, 24, and 32 ng/ml, respectively, were evaluated using (i) the comet assay, (ii) the nuclear division index (NDI), (iii) the micronucleus test (CBMN) and (iv) cell proliferation curves generated by quantifying cell numbers and protein levels. In this study, 1520 to 3420 ng/ml CsA decreased cell viability after 48 h of exposure. Genotoxic effects were observed only with a concentration of 1520 ng/ml after 3h of exposure and with concentrations of 675 and 1520 ng/ml after 24h of exposure. Mutagenic effects were observed only for the concentration of 1520 ng/ml. FK-506 decreased cell viability after 72 h of exposure for concentrations up to 20 ng/ml; genotoxic effects were observed with concentrations up to 8 ng/ml for both treatment times (3 and 24h) and mutagenic effects were observed with concentrations of 24 and 32 ng/ml after 24h of treatment. The cell proliferation curves demonstrated the absence of cytostatic effects of these drugs, and these data were confirmed by the NDI analysis. Our results suggest that concentrations lower than 300 ng/ml of CsA and 16 ng/ml of FK-506 are safe for use, as they did not induce genotoxic and mutagenic damage or affect MRC-5 cell viability and proliferation.

  19. Single and combined genotoxicity effects of six pollutants on THP-1 cells.

    PubMed

    Xiao, Dan; Wang, Haiyan; Han, Daxiong

    2016-09-01

    The objective of this study was to evaluate the single and combined genotoxic effects of six food pollutants (Chrysoidine G, Sudan I, acid orange II, malachite green, acrylamide, and potassium bromate) on THP-1 cells through comet assay. The results of the single tests indicated that the pollutants increased the percentage of tail DNA (% tail DNA) in a dose-dependent manner. Moreover, the % tail DNA values induced by synthetic colorants (Chrysoidine G, Sudan I, acid orange II, and malachite green) were significantly higher than those by acrylamide or potassium bromate at most concentrations. In the combined tests, Chrysoidine G (422 μmol/L) or acrylamide (400 μmol/L) was mixed with different concentrations of the other five pollutants respectively. In the first combined tests, most mixtures significantly increased the % tail DNA values with the exception of Chrysoidine G and acid orange II. In the second tests, there were no significant differences in the % tail DNA values between the single and combined tests at most cases. PMID:27375233

  20. Effects of boric acid and borax on titanium dioxide genotoxicity.

    PubMed

    Turkez, Hasan

    2008-07-01

    Titanium dioxide (TiO(2)) is a potential carcinogenic/mutagenic agent although it is used in many areas including medical industries and cosmetics. Boron (as boric acid and borax) has also well-described biological effects and therapeutic benefits. In a previous study, sister-chromatid exchanges (SCEs) and micronuclei (MN) rates were assessed in control and TiO(2)-treated (1, 2, 3, 5, 7.5 and 10 microm) human whole blood cultures. The results showed that the rates of SCE (at 2, 3, 5, 7.5 and 10 microm) and MN (at 5, 7.5 and 10 microm) formation in peripheral lymphocytes were increased significantly by TiO(2) compared with the controls. The present study also investigated the genetic effects of boric acid and borax (2.5, 5 and 10 microm) on cultures with and without TiO(2) addition. No significant increase in SCE and MN frequencies were observed at all concentrations of boron compounds. However, TiO(2)-induced SCE and MN could be reduced significantly by the presence of boric acid and borax. In conclusion, this study indicated for the first time that boric acid and borax led to an increased resistance of DNA to damage induced by TiO(2).

  1. Evaluation of the genotoxic effects of the boron neutron capture reaction in human melanoma cells using the cytokinesis block micronucleus assay.

    PubMed

    Oliveira, N G; Castro, M; Rodrigues, A S; Gonçalves, I C; Cassapo, R; Fernandes, A P; Chaveca, T; Toscano-Rico, J M; Rueff, J

    2001-09-01

    The present work reports on the genotoxicity of the boron neutron capture (BNC) reaction in human metastatic melanoma cells (A2058) assessed by the cytokinesis block micronucleus assay (CBMN) using p-borono-L-phenylalanine (BPA) as the boron delivery agent. Different concentrations of BPA (0.48, 1.2 and 2.4 mM) and different fluences of thermal neutrons were studied. Substantial genotoxic potential of alpha and lithium particles generated inside or near the malignant cell by the BNC reaction was observed in a dose-response manner as measured by the frequency of micronucleated binucleated melanoma cells and by the number of micronuclei (MN) per binucleated cell. The distribution of the number of MN per micronucleated binucleated cell was also studied. The BNC reaction clearly modifies this distribution, increasing the frequency of micronucleated cells with 2 and, especially, > or =3 MN and conversely decreasing the frequency of micronucleated cells with 1 MN. A decrease in cell proliferation was also observed which correlated with MN formation. A discrete genotoxic and anti-proliferative contribution from both thermal neutron irradiation and BPA was observed and should be considered secondary. Additionally, V79 Chinese hamster cells (chromosomal aberrations assay) and human lymphocytes (CBMN assay) incubated with different concentrations of BPA alone did not show any evidence of genotoxicity. The presented results reinforce the usefulness of the CBMN assay as an alternative method for assessment of the deleterious effects induced by high LET radiation produced by the BNC reaction in human melanoma cells.

  2. Genotoxic effects of eugenol, isoeugenol and safrole in the wing spot test of Drosophila melanogaster.

    PubMed

    Munerato, Maria Cristina; Sinigaglia, Marialva; Reguly, Maria Luíza; de Andrade, Heloísa Helena Rodrigues

    2005-04-01

    In the present study, the phenolic compounds eugenol, isoeugenol and safrole were investigated for genotoxicity in the wing spot test of Drosophila melanogaster. The Drosophila wing somatic mutation and recombination test (SMART) provides a rapid means to evaluate agents able to induce gene mutations and chromosome aberrations, as well as rearrangements related to mitotic recombination. We applied the SMART in its standard version with normal bioactivation and in its variant with increased cytochrome P450-dependent biotransformation capacity. Eugenol and safrole produced a positive recombinagenic response only in the improved assay, which was related to a high CYP450-dependent activation capacity. This suggests, as previously reported, the involvement of this family of enzymes in the activation of eugenol and safrole rather than in its detoxification. On the contrary, isoeugenol was clearly non-genotoxic at the same millimolar concentrations as used for eugenol in both the crosses. The responsiveness of SMART assays to recombinagenic compounds, as well as the reactive metabolites from eugenol and safrole were considered responsible for the genotoxicity observed.

  3. Genotoxic Effects of Superconducting Static Magnetic Fields (SMFs) on Wheat (Triticum aestivum) Pollen Mother Cells (PMCs)

    NASA Astrophysics Data System (ADS)

    Zhang, Pingping; Yin, Ruochun; Chen, Zhiyou; Wu, Lifang; Yu, Zengliang

    2007-04-01

    The effects of superconducting static magnetic fields (SMFs) on the pollen mother cells (PMCs) of wheat were investigated in order to evaluate the possible genotoxic effect of such non-ionizing radiation. The seeds of wheat were exposed to static magnetic fields with either different magnetic flux densities (0, 1, 3, 5 and 7 Tesla) for 5 h or different durations (1, 3 and 5 h) at a magnetic flux density of 7 Tesla. The seeds were germinated at 23oC after exposure and the seedlings were transplanted into the field. The PMCs from young wheat ears were taken and slides were made following the conventional method. The genotoxic effect was evaluated in terms of micronucleus (MN), chromosomal bridge, lagging chromosome and fragments in PMCs. Although the exposed groups of a low field intensity (below 5 Tesla) showed no statistically significant difference in the aberration frequency compared with the unexposed control groups and sham exposed groups, a significant increase in the chromosomal bridge, lagging chromosome, triple-polar segregation or micronucleus was observed at a field strength of 5 Tesla or 7 Tesla, respectively. The analysis of dose-effect relationships indicated that the increased frequency of meiotic abnormal cells correlated with the flux density of the magnetic field and duration, but no linear relationship was observed. Such statistically significant differences indicated a potential genotoxic effect of high static magnetic fields above 5 T.

  4. Genotoxic effects of water from São Francisco River, Brazil, in Astyanax paranae.

    PubMed

    Ribeiro, Diego Luis; Barcelos, Gustavo Rafael Mazzaron; d'Arce, Luciana Paula Grégio

    2014-09-01

    Aquatic monitoring is an important tool for identifying potential compounds in rivers that may damage the environment. Here, we evaluate the potential genotoxic effects of water samples from São Francisco River (Brazil) using the micronuclei (MN) assay in resident species, Astyanax paranae. Four seasonal collections occurred between the years 2009 and 2010, at three locations between two nearby cities in the region. It was clearly observed an increase of MN frequency in fish caught in the river. This result is most likely due to the sewage contamination from the treatment plant, the waste pesticides from crops and the lack of riparian vegetation along the river, especially during the winter when there was a significant increase in the frequencies of MN. These results indicate that compounds in waters from São Francisco River may have genotoxic effects and consequently, cause damage to the environment as well as to human health. PMID:24849712

  5. Genotoxic effects of water from São Francisco River, Brazil, in Astyanax paranae.

    PubMed

    Ribeiro, Diego Luis; Barcelos, Gustavo Rafael Mazzaron; d'Arce, Luciana Paula Grégio

    2014-09-01

    Aquatic monitoring is an important tool for identifying potential compounds in rivers that may damage the environment. Here, we evaluate the potential genotoxic effects of water samples from São Francisco River (Brazil) using the micronuclei (MN) assay in resident species, Astyanax paranae. Four seasonal collections occurred between the years 2009 and 2010, at three locations between two nearby cities in the region. It was clearly observed an increase of MN frequency in fish caught in the river. This result is most likely due to the sewage contamination from the treatment plant, the waste pesticides from crops and the lack of riparian vegetation along the river, especially during the winter when there was a significant increase in the frequencies of MN. These results indicate that compounds in waters from São Francisco River may have genotoxic effects and consequently, cause damage to the environment as well as to human health.

  6. A review of the genotoxic and carcinogenic effects of aspartame: does it safe or not?

    PubMed

    Yılmaz, Serkan; Uçar, Aslı

    2014-12-01

    The objective of this article is to review genotoxicologic and carcinogenic profile of the artificial sweetener aspartame. Aspartame is a synthetic dipeptide, nearly 180-200 times sweeter than sucrose. It is the most widely used artificial sweetener especially in carbonated and powdered soft drinks, beverages, drugs and hygiene products. There is a discussion ongoing for many years whether aspartame posses genotoxic and carcinogenic risk for humans. This question led to many studies to specify the adverse effects of aspartame. Therefore, we aimed to review the oldest to latest works published in major indices to gather information within this article. With respect to published data, genotoxicity and carcinogenicity of aspartame is still confusing. So, consumers should be aware of the potential side effects of aspartame before they consume it.

  7. The Combined Toxic and Genotoxic Effects of Cd and As to Plant Bioindicator Trifolium repens L

    PubMed Central

    Ghiani, Alessandra; Fumagalli, Pietro; Nguyen Van, Tho; Gentili, Rodolfo; Citterio, Sandra

    2014-01-01

    This study was undertaken to investigate combined toxic and genotoxic effects of cadmium (Cd) and arsenic (As) on white clover, a pollutant sensitive plant frequently used as environmental bioindicator. Plants were exposed to soil spiked with increasing concentrations of cadmium sulfate (20, 40 and 60 mg Kg−1) or sodium arsenite (5, 10 and 20 mg Kg−1) as well as with their combinations. Metal(loid) bioavailability was assessed after soil contamination, whereas plant growth, metal(loid) concentration in plant organs and DNA damage were measured at the end of plant exposition. Results showed that individual and joint toxicity and genotoxicity were related to the concentration of Cd and As measured in plant organs, and that As concentration was the most relevant variable. Joint effects on plant growth were additive or synergistic, whereas joint genotoxic effects were additive or antagonistic. The interaction between Cd and As occurred at both soil and plant level. In soil the presence of As limited the bioavailability of Cd, whereas the presence of Cd increased the bioavailability of As. Nevertheless only As biovailability determined the amount of As absorbed by plants. The amount of Cd absorbed by plant was not linearly correlated with the fraction of bioavailable Cd in soil suggesting the involvement of additional factors, such as plant uptake mechanisms. These results reveal that the simultaneous presence in soil of Cd and As, although producing an additive or synergistic toxic effect on Trifolium repens L. growth, generates a lower DNA damage. PMID:24914541

  8. The genotoxic effects of benzo[a]pyrene and methamidophos on black porgy evaluated by comet assay

    NASA Astrophysics Data System (ADS)

    Liu, Rixian; Hong, Huasheng; Wang, Xinhong; Wang, Kejian; Wang, Chunguang

    2005-12-01

    In this study, two common pollutants (benzo[a]pyrene and methamidophos) in marine environment were tested by comet assay for their inducement of in vivo genotoxic effect to the blood cells of black porgy ( Acanthopagrus schlegeli). The fish was exposed to 2 μg/L of benzo[a]pyrene (BaP) and methamidophos, and their mixture. The assay was performed on whole blood at 2 h, 5 h, 24 h and 96 h exposure intervals. A significant increase in DNA damage was observed in each treatment with the pollutants. Additive effect of BaP and methamidophos was also found in the experiment. However, the decrease ratios of DNA damage for 5 h and 96 h exposure interals compared with 2 h and 24 h exposure ones, respectively, were noticed. This phenomenon may be explained by the function of repairing process via enzyme cytochrome P450 in the animal. Evidence of the genotoxicity of organophosphorus pesticides (OPs) and polynuclear aromatic hydrocarbons (PAHs) on marine fish are discussed in this paper.

  9. Control and target gene selection for studies on UV-induced genotoxicity in whales

    PubMed Central

    2013-01-01

    on the capacity of wildlife to resolve or limit UV-induced damage. The proposed target genes are HSP70, P53 and KIN, known to be involved in genotoxic stress pathways, and whose expression patterns can be accurately assessed by using two stable control genes, RPL4 and RPS18. PMID:23837727

  10. Genotoxic effects of water pollution on two fish species living in Karasu River, Erzurum, Turkey.

    PubMed

    Yazıcı, Zehra; Sişman, Turgay

    2014-11-01

    Karasu River, which is the only river in the Erzurum plain, is the source of the Euphrates River (Eastern Anatolia of Turkey). The river is in a serious environmental situation as a result of pollution by agricultural and industrial sewage and domestic discharges. The present study aims to evaluate genotoxic effects of toxic metals in chub, Leuciscus cephalus, and transcaucasian barb, Capoeta capoeta, collected from contaminated site of the Karasu River, in comparison with fish from an unpolluted reference site. Heavy metal concentrations in surface water of the river were determined. The condition factor (CF) was taken as a general biomarker of the health of the fish, and genotoxicity assays such as micronucleus (MN) and other nuclear abnormalities (NA) were carried out on the fish species studied. MN and NA such as kidney-shaped nucleus, notched nucleus, binucleated, lobed nucleus, and blebbed nucleus were assessed in peripheral blood erythrocytes, gill epithelial cells, and liver cells of the fish. A significant decrease in CF values associated with a significant elevation in MN and NA frequencies was observed in fish collected from the polluted sites compared with those from the reference site. Results of the current study show the significance of integrating a set of biomarkers to identify the effects of anthropogenic pollution. High concentrations of heavy metals have a potential genotoxic effects, and the toxicity is possibly related to industrial, agricultural, and domestic activities.

  11. Helicobacter pylori infection and antioxidants can modulate the genotoxic effects of heterocyclic amines in gastric mucosa cells.

    PubMed

    Poplawski, Tomasz; Chojnacki, Cezary; Czubatka, Anna; Klupinska, Grazyna; Chojnacki, Jan; Blasiak, Janusz

    2013-08-01

    Helicobacter pylori (H. pylori) infection plays an important role in gastric carcinogenesis. This bacterium may induce cancer transformation and change the susceptibility of gastric mucosa cells to various exogenous dietary irritants. The aim of the study was to evaluate the influence of H. pylori infection on the reaction of the stomach cells to a genotoxic effect of heterocyclic amines (HCAs). These well-known mutagens are formed during cooking of protein-rich foods, primarily meat. Taking into account that persons consuming a mixed-western diet are exposed to these compound nearly an entire lifetime and more than half of human population is infected with H. pylori, it is important to assess the combined effect of H. pylori infection and HCAs in the context of DNA damage in gastric mucosa cells, which is a prerequisite to cancer transformation. We employed 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,8-dimethyl-imidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) because these substances are present in a great amount in cooked and fried meat. Using alkaline comet assay, we showed that the extent of the DNA damage induced by HCAs was significantly higher in H. pylori infected gastric mucosa cells than in non-infected counterparts. We did not observed any difference in the efficiency of repair of DNA lesions induced by HCAs in both type of cells. Vitamin C reduced the genotoxic effects of HCAs in H. pylori infected and non-infected gastric mucosa cells. Melatonin more effectively decreased DNA damage caused by HCAs in H. pylori infected gastric mucosa cells as compared with control. Our results suggest that H. pylori infection may influence the susceptibility of gastric mucosa cells to HCAs and dietary antioxidative substances, including vitamin C and melatonin may inhibit the genotoxic effects of HCAs on gastric mucosa cells and may reduce the risk of carcinogenesis caused by food borne mutagens and H. pylori

  12. Genotoxic effects of linear alkyl benzene sulfonate, sodium pentachlorophenate and dichromate on Tetrahymena pyriformis.

    PubMed

    Wu, Y; Shen, Y

    1992-01-01

    DNA in macro- and micronuclei of Tetrahymena pyriformis treated with linear alkyl benzene sulfonate (LAS) and sodium pentachlorophenate (PCP-Na) were determined by microspectrophotometry. The effects on rate of formation of macronuclear DNA extrusion bodies were also studied. We found DNA content of micronuclei in 0.14 ppm LAS and 0.9 ppb PCP-Na was lower than in that of the control, and LAS was able to increase the formation rate of macronuclear DNA extrusion bodies (the formation rate was 54% in 11.3 ppm LAS and 25.6% in 16.7 ppm dichromate). We concluded that 0.14 ppm LAS (below the maximum acceptable toxicant concentration) was genotoxic, whereas 0.014 ppm LAS was not. Dichromate 0.05 ppm and 0.9 ppb PCP-Na, equal to and below the maximum acceptable toxicant concentration, respectively, were potentially genotoxic.

  13. In vitro evaluation of genotoxic effects under magnetic resonant coupling wireless power transfer.

    PubMed

    Mizuno, Kohei; Shinohara, Naoki; Miyakoshi, Junji

    2015-04-01

    Wireless power transfer (WPT) technology using the resonant coupling phenomenon has been widely studied, but there are very few studies concerning the possible relationship between WPT exposure and human health. In this study, we investigated whether exposure to magnetic resonant coupling WPT has genotoxic effects on WI38VA13 subcloned 2RA human fibroblast cells. WPT exposure was performed using a helical coil-based exposure system designed to transfer power with 85.4% efficiency at a 12.5-MHz resonant frequency. The magnetic field at the positions of the cell culture dishes is approximately twice the reference level for occupational exposure as stated in the International Commission on Non-Ionizing Radiation Protection (ICNIRP) guidelines. The specific absorption rate at the positions of the cell culture dishes matches the respective reference levels stated in the ICNIRP guidelines. For assessment of genotoxicity, we studied cell growth, cell cycle distribution, DNA strand breaks using the comet assay, micronucleus formation, and hypoxanthine-guanine phosphoribosyltransferase (HPRT) gene mutation, and did not detect any significant effects between the WPT-exposed cells and control cells. Our results suggest that WPT exposure under the conditions of the ICNIRP guidelines does not cause detectable cellular genotoxicity. PMID:25853218

  14. In Vitro Evaluation of Genotoxic Effects under Magnetic Resonant Coupling Wireless Power Transfer

    PubMed Central

    Mizuno, Kohei; Shinohara, Naoki; Miyakoshi, Junji

    2015-01-01

    Wireless power transfer (WPT) technology using the resonant coupling phenomenon has been widely studied, but there are very few studies concerning the possible relationship between WPT exposure and human health. In this study, we investigated whether exposure to magnetic resonant coupling WPT has genotoxic effects on WI38VA13 subcloned 2RA human fibroblast cells. WPT exposure was performed using a helical coil-based exposure system designed to transfer power with 85.4% efficiency at a 12.5-MHz resonant frequency. The magnetic field at the positions of the cell culture dishes is approximately twice the reference level for occupational exposure as stated in the International Commission on Non-Ionizing Radiation Protection (ICNIRP) guidelines. The specific absorption rate at the positions of the cell culture dishes matches the respective reference levels stated in the ICNIRP guidelines. For assessment of genotoxicity, we studied cell growth, cell cycle distribution, DNA strand breaks using the comet assay, micronucleus formation, and hypoxanthine-guanine phosphoribosyltransferase (HPRT) gene mutation, and did not detect any significant effects between the WPT-exposed cells and control cells. Our results suggest that WPT exposure under the conditions of the ICNIRP guidelines does not cause detectable cellular genotoxicity. PMID:25853218

  15. Genotoxic effects of commercial formulations of Chlorpyrifos and Tebuconazole on green algae.

    PubMed

    Martinez, Ricardo Santiago; Di Marzio, Walter Darío; Sáenz, María Elena

    2015-01-01

    The alkaline single-cell gel electrophoresis assay (comet assay) was used for the study of the genotoxic effects of insecticide Chlorpyrifos and fungicide Tebuconazole (commercial formulations) on two freshwater green algae species, Pseudokirchneriella subcapitata and Nannocloris oculata, after 24 h of exposure. The percentage of DNA in tail of migrating nucleoids was taken as an endpoint of DNA impairment. Cell viability was measured by fluorometric detection of chlorophyll "a" in vivo and the determination of cell auto-fluorescence. Only the higher concentration of Chlorpyrifos tested resulted to affect significantly the cell viability of P. subcapitata, whereas cells of N. oculata were not affected. Tebuconazole assayed concentrations (3 and 6 mg/l) did not affect cell viability of both species. The results of comet assay on P. subcapitata showed that Chlorpyrifos concentration evaluated (0.8 mg/l) exerted a genotoxic effects; while for the other specie a concentration of 10 mg/l was needed. Tebuconazole was genotoxic at 3 and 6 mg/l for both species. The comet assay evidenced damage at the level of DNA simple strains molecule at pesticide concentrations were cytotoxicity was not evident, demonstrating that algae are models to take into account in ecological risk assessments for aquatic environments. PMID:25230876

  16. Bioaccumulation of nickel and its biochemical and genotoxic effects on juveniles of the neotropical fish Prochilodus lineatus.

    PubMed

    Palermo, Francine F; Risso, Wagner E; Simonato, Juliana D; Martinez, Claudia B R

    2015-06-01

    Juveniles of the freshwater fish Prochilodus lineatus were exposed to three concentrations of nickel (Ni): 25, 250 and 2500 µg L(-1) or water only for periods of 24 and 96 h to test for Ni bioaccumulation, its effects on antioxidant defenses and metallothioneins, and the occurrence of DNA damage. After exposure, the fish were sampled and tissue removed from the gills, liver, kidney and muscle to test for Ni accumulation and conduct biochemical (gills and liver) and genotoxic (blood cells and gills) analyses. The results showed that Ni accumulates in the organs in different proportions (kidney>liver>gills>muscle) and accumulation varied according to exposure time. Metallothionein (MT) levels increased in the liver and gills after exposure to Ni, implying that the presence of Ni in these tissues could induce MT synthesis. We also observed that Ni exposure affected antioxidant defenses, increasing lipid peroxidation in the liver of fish exposed to Ni for 96 h at the highest concentration tested. DNA damage increased in both blood cells and gills of fish exposed to all Ni concentrations, indicating the genotoxic potential of Ni on fish. We therefore concluded that Ni accumulates in various tissues and results in oxidative and DNA damage in P. lineatus, and that the maximum permitted Ni concentration set in Brazilian legislation (25 µg L(-1)) for freshwaters is not safe for this species. PMID:25744913

  17. In vivo and in vitro exposures for the evaluation of the genotoxic effects of lead on the Neotropical freshwater fish Prochilodus lineatus.

    PubMed

    Monteiro, V; Cavalcante, D G S M; Viléla, M B F A; Sofia, S H; Martinez, C B R

    2011-08-01

    In the present study, in vivo and in vitro exposures were used to assess the genotoxicity of lead (Pb) to the freshwater fish Prochilodus lineatus. The comet assay using blood, liver and gill cells, and the occurrence of micronuclei (MN) and other erythrocytic nuclear abnormalities (ENA) were used to assess the genotoxic potential of lead in vivo. Metallothionein content (MT) was measured in fish liver in order to evaluate the protection of fish against Pb toxicity. Fish erythrocytes were exposed to Pb in vitro (1, 3 and 6 h) and the number of viable cells, DNA integrity, using the comet assay, and lysosomal membrane stability, measured by the neutral red retention assay (NRRA) were analyzed. The results of the comet assay after in vivo toxicity tests (6, 24 and 96 h) showed that Pb was genotoxic for all the three tissues analyzed after 96 h exposure. A significant increase in liver MT content was observed after 6 and 24 h of Pb exposure. MN frequency did not increase after Pb exposures, but the frequency of the other ENA, such as kidney-shaped nuclei, segmented nuclei and lobed nuclei, showed a significant increase after 24 and 96 h, indicating that ENA is a better biomarker for Pb exposure than MN alone after short-term exposures. The results of the comet assay performed with erythrocytes in vitro exposed to lead confirmed its genotoxic effect and showed that DNA damage increased with increasing exposure time. Moreover, the NRRA clearly indicated that Pb induces a destabilization of the lysosomal membrane. These results demonstrate the potential genotoxicity and cytotoxicity of lead after acute exposures.

  18. Further evidence against a direct genotoxic mode of action for arsenic-induced cancer

    SciTech Connect

    Klein, Catherine B.; Leszczynska, Joanna; Hickey, Christina; Rossman, Toby G.

    2007-08-01

    Arsenic in drinking water, a mixture of arsenite and arsenate, is associated with increased skin and other cancers in Asia and Latin America, but not the United States. Arsenite alone in drinking water does not cause skin cancers in experimental animals; therefore, it is not a complete carcinogen in skin. We recently showed that low concentrations of arsenite enhanced the tumorigenicity of solar UV irradiation in hairless mice, suggesting arsenic cocarcinogenesis with sunlight in skin cancer and perhaps with different carcinogenic partners for lung and bladder tumors. Cocarcinogenic mechanisms could include blocking DNA repair, stimulating angiogenesis, altering DNA methylation patterns, dysregulating cell cycle control, induction of aneuploidy and blocking apoptosis. Arsenicals are documented clastogens but not strong mutagens, with weak mutagenic activity reported at highly toxic concentrations of inorganic arsenic. Previously, we showed that arsenite, but not monomethylarsonous acid (MMA[III]), induced delayed mutagenesis in HOS cells. Here, we report new data on the mutagenicity of the trivalent methylated arsenic metabolites MMA(III) and dimethylarsinous acid [DMA(III)] at the gpt locus in Chinese hamster G12 cells. Both methylated arsenicals seemed mutagenic with apparent sublinear dose responses. However, significant mutagenesis occurred only at highly toxic concentrations of MMA(III). Most mutants induced by MMA(III) and DMA(III) exhibited transgene deletions. Some non-deletion mutants exhibited altered DNA methylation. A critical discussion of cell survival leads us to conclude that clastogenesis occurs primarily at highly cytotoxic arsenic concentrations, casting further doubt as to whether a genotoxic mode of action (MOA) for arsenicals is supportable.

  19. Hospital waste incinerator bottom ash leachate induced cyto-genotoxicity in Allium cepa and reproductive toxicity in mice.

    PubMed

    Akinbola, Temitayo I; Adeyemi, Adetutu; Morenikeji, Olajumoke A; Bakare, Adekunle A; Alimba, Chibuisi G

    2011-07-01

    The potentials of hospital incinerator bottom ash leachate (HIBAL) to induce cyto-genotoxicity in Allium cepa and reproductive anomalies in the mouse were investigated. The leachate obtained from simulation of the bottom ash was analyzed for some physico-chemical parameters. The A. cepa, mouse sperm morphology and histopathological tests were carried out at concentrations ranging from 1% to 50% of the leachate sample. In A. cepa, HIBAL caused significant (p < 0.05) inhibition of root growth and induction of chromosomal aberrations. In the animal assays, there was 100% mortality at the 50% concentrations. The leachate caused insignificant (p > 0.05) concentration-dependent induction of various types of sperm morphology. There was accumulation of fluid in the seminiferous tubule lumen and necrosis of stem cells in the testes. These effects were believed to be provoked by the somatic and germ cell genotoxins, particularly the heavy metals in the leachate. Our finding is of environmental and public health significance. PMID:21343229

  20. Genetic toxicology of phthalate esters: mutagenic and other genotoxic effects.

    PubMed Central

    Douglas, G R; Hugenholtz, A P; Blakey, D H

    1986-01-01

    The effects of DEHP on sperm morphology and on peripheral blood micronuclei were studied for 12 weeks following five subacute IP injections of DEHP at 1/6, 1/12, and 1/60 of the LD50 per day. Sperm morphology was examined in both adult mice and rats, while peripheral blood micronuclei were scored in mice up to 4 weeks after treatment. In mice, DEHP at 1/6 LD50 significantly depressed body weight gain for up to 12 weeks after treatment, and reduced epididymal sperm number by 4 weeks. Numbers of morphologically abnormal sperm did not differ from controls in the 12 weeks following treatment. In addition, DEHP did not increase the numbers of peripheral blood micronuclei. Studies in the rat indicated that exposure to doses of 1/6 and 1/12 of the LD50 per day of DEHP resulted in a reduced gain in body weight compared to controls. Testis weight, sperm number, and numbers of morphologically abnormal sperm were unaffected by DEHP following treatment. In separate experiments, DEHP did not induce sister chromatid exchange (SCE) or DNA damage in Chinese hamster ovary (CHO) cells. Although DEHP is known to cause testicular atrophy in rats and to a lesser extent in mice, it did not cause an increase in abnormal sperm in either species. Together with the CHO and micronucleus data, these findings suggest that DEHP has a low probability of causing genetic damage capable of being transmitted through the male germ line. PMID:3709450

  1. Genotoxicity of aspartame.

    PubMed

    Rencüzoğullari, Eyyüp; Tüylü, Berrin Ayaz; Topaktaş, Mehmet; Ila, Hasan Basri; Kayraldiz, Ahmet; Arslan, Mehmet; Diler, Songül Budak

    2004-08-01

    In the present study, the genotoxic effects of the low-calorie sweetener aspartame (ASP), which is a dipeptide derivative, was investigated using chromosome aberration (CA) test, sister chromatid exchange (SCE) test, micronucleus test in human lymphocytes and also Ames/Salmonella/ microsome test. ASP induced CAs at all concentrations (500, 1000 and 2000 microg/ml) and treatment periods (24 and 48 h) dose-dependently, while it did not induce SCEs. On the other hand, ASP decreased the replication index (RI) only at the highest concentration for 48 h treatment period. However, ASP decreased the mitotic index (MI) at all concentrations and treatment periods dose-dependently. In addition, ASP induced micronuclei at the highest concentrations only. This induction was also dose-dependent for 48 hours treatment period. ASP was not mutagenic for Salmonella typhimurium TA98 and TA100 strains in the absence and presence of S9 mix.

  2. Genotoxic effects of catmint (Nepeta meyeri Benth.) essential oils on some weed and crop plants.

    PubMed

    Kekeç, Güzin; Mutlu, Salih; Alpsoy, Lokman; Sakçali, M Serdal; Atici, Ökkes

    2013-07-01

    This study investigates the genotoxicity of the essential oils extracted from the aerial parts of catmint (Nepeta meyeri Benth.) against two weeds (Bromus danthoniae and Lactuca serriola) and two crop plants (Brassica napus and Zea mays). The essential oils of N. meyeri analyzed by gas chromatography-mass spectrometry contained 14 compounds, with 4aα, 7α, 7aβ-nepetalactone (83.4%), 4aα, 7α, and 7aα-nepetalactone (8.83%) as the major components. The oils were diluted (25, 50, 100, and 150 ppm) and the solutions were applied to seeds or leaves of these plants. The study compared the germination percentage and random amplified polymorphic DNA (RAPD) results with the control group. The results showed that the oils had a strong inhibitory activity and caused a change in RAPD profiles in terms of variation in band intensity, loss of bands, and appearance of new bands compared with the control group. The results suggested that RAPD analysis could be applied as a suitable biomarker assay for the detection of genotoxic effects of plant allelochemicals. This study indicates the genotoxical potential of N. meyeri essential oils on weed and crop plants.

  3. Genotoxic effects of catmint (Nepeta meyeri Benth.) essential oils on some weed and crop plants.

    PubMed

    Kekeç, Güzin; Mutlu, Salih; Alpsoy, Lokman; Sakçali, M Serdal; Atici, Ökkes

    2013-07-01

    This study investigates the genotoxicity of the essential oils extracted from the aerial parts of catmint (Nepeta meyeri Benth.) against two weeds (Bromus danthoniae and Lactuca serriola) and two crop plants (Brassica napus and Zea mays). The essential oils of N. meyeri analyzed by gas chromatography-mass spectrometry contained 14 compounds, with 4aα, 7α, 7aβ-nepetalactone (83.4%), 4aα, 7α, and 7aα-nepetalactone (8.83%) as the major components. The oils were diluted (25, 50, 100, and 150 ppm) and the solutions were applied to seeds or leaves of these plants. The study compared the germination percentage and random amplified polymorphic DNA (RAPD) results with the control group. The results showed that the oils had a strong inhibitory activity and caused a change in RAPD profiles in terms of variation in band intensity, loss of bands, and appearance of new bands compared with the control group. The results suggested that RAPD analysis could be applied as a suitable biomarker assay for the detection of genotoxic effects of plant allelochemicals. This study indicates the genotoxical potential of N. meyeri essential oils on weed and crop plants. PMID:22434692

  4. Dose-Response for Multiple Biomarkers of Exposure and Genotoxic Effect Following Repeated Treatment of Rats with the Alkylating Agents, MMS and MNU.

    PubMed

    Ji, Zhiying; LeBaron, Matthew J; Schisler, Melissa R; Zhang, Fagen; Bartels, Michael J; Gollapudi, B Bhaskar; Pottenger, Lynn H

    2016-05-01

    The nature of the dose-response relationship for various in vivo endpoints of exposure and effect were investigated using the alkylating agents, methyl methanesulfonate (MMS) and methylnitrosourea (MNU). Six male F344 rats/group were dosed orally with 0, 0.5, 1, 5, 25 or 50mg/kg bw/day (mkd) of MMS, or 0, 0.01, 0.1, 1, 5, 10, 25 or 50 mkd of MNU, for 4 consecutive days and sacrificed 24h after the last dose. The dose-responses for multiple biomarkers of exposure and genotoxic effect were investigated. In MMS-treated rats, the hemoglobin adduct level, a systemic exposure biomarker, increased linearly with dose (r (2) = 0.9990, P < 0.05), indicating the systemic availability of MMS; however, the N7MeG DNA adduct, a target exposure biomarker, exhibited a non-linear dose-response in blood and liver tissues. Blood reticulocyte micronuclei (MN), a genotoxic effect biomarker, exhibited a clear no-observed-genotoxic-effect-level (NOGEL) of 5 mkd as a point of departure (PoD) for MMS. Two separate dose-response models, the Lutz and Lutz model and the stepwise approach using PROC REG both supported a bilinear/threshold dose-response for MN induction. Liver gene expression, a mechanistic endpoint, also exhibited a bilinear dose-response. Similarly, in MNU-treated rats, hepatic DNA adducts, gene expression changes and MN all exhibited clear PoDs, with a NOGEL of 1 mkd for MN induction, although dose-response modeling of the MNU-induced MN data showed a better statistical fit for a linear dose-response. In summary, these results provide in vivo data that support the existence of clear non-linear dose-responses for a number of biologically significant events along the pathway for genotoxicity induced by DNA-reactive agents.

  5. Chronic dietary exposure of zebrafish to PAH mixtures results in carcinogenic but not genotoxic effects.

    PubMed

    Larcher, T; Perrichon, P; Vignet, C; Ledevin, M; Le Menach, K; Lyphout, L; Landi, L; Clerandeau, C; Lebihanic, F; Ménard, D; Burgeot, T; Budzinski, H; Akcha, F; Cachot, J; Cousin, X

    2014-12-01

    Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous contaminants that can be present at high levels as mixtures in polluted aquatic environments. Many PAHs are potent mutagens and several are well-known carcinogens. Despite numerous studies on individual compounds, little is known about the toxicity of PAHs mixtures that are encountered in environmental situations. In the present work, zebrafish were continuously fed from 5 days post-fertilisation to 14 months post-fertilisation (mpf) with a diet spiked with fractions of either pyrolytic (PY), petrogenic light oil (LO), or petrogenic heavy oil (HO) origin at three concentrations. A decrease in survival was identified after 3 mpf in fish fed with the highest concentration of HO or LO, but not for PY. All PAH fractions caused preneoplastic and neoplastic disorders in long-term-exposed animals. Target tissues were almost exclusively of epithelial origin, with the bile duct epithelium being the most susceptible to chronic exposure to all PAH fractions, and with germ cells being the second most responsive cells. Significantly higher incidences of neoplasms were observed with increasing PAH concentration and exposure duration. The most severe carcinogenic effects were induced by dietary exposure to HO compared to exposure to LO or PY (45, 30 and 7 %, respectively, after 9 to 10 months of exposure to an intermediate concentration of PAHs). In contrast, earliest carcinogenic effects were detected as soon as 3 mpf after exposure to LO, including the lowest concentration, or to PY. PAH bioactivation and genotoxicity in blood was assessed by ethoxyresorufin-O-deethylase activity quantification and comet and micronuclei assays, respectively, but none of these were positive. Chronic dietary exposure of zebrafish to PAH mixtures results in carcinogenotoxic events that impair survival and physiology of exposed fish.

  6. The in vitro genotoxic effects of a commercial formulation of alpha-cypermethrin in human peripheral blood lymphocytes.

    PubMed

    Kocaman, Ayşe Yavuz; Topaktaş, Mehmet

    2009-01-01

    alpha-Cypermethrin, a highly active pyrethroid insecticide, is effective against a wide range of insects encountered in agriculture and animal husbandry. The potential genotoxicity of a commercial formulation of alpha-cypermethrin (Fastac 100 EC, containing 10% alpha-cypermethrin as the active ingredient) on human peripheral lymphocytes was examined in vitro by sister chromatid exchange (SCE), chromosomal aberrations (CAs), and micronucleus (MN) tests. The human lymphocytes were treated with 5, 10, 15, and 20 microg/ml of alpha-cypermethrin for 24- and 48-hr. alpha-Cypermethrin induced SCEs and CAs significantly at all concentrations and treatment times and MN formation was significantly induced at 5 and 10 microg/ml of alpha-cypermethrin when compared with both the control and solvent control. Binuclear cells could not be detected sufficiently in the highest two concentration of alpha-cypermethrin (15 and 20 microg/ml) for both the 24- and 48-hr treatment times. alpha-Cypermethrin decreased the proliferation index (PI) at three high concentrations (10, 15, and 20 microg/ml) for both treatment periods as compared with the control groups. In addition, alpha-cypermethrin reduced both the mitotic index (MI) and nuclear division index (NDI) significantly at all concentrations for two treatment periods. The PI and MI were reduced by alpha-cypermethrin in a concentration-dependent manner during both treatment times. In general, alpha-cypermethrin showed higher cytotoxic and cytostatic effects than positive control (MMC) at the two highest concentrations for the 24- and 48-hr treatment periods. The present study is the first to report the genotoxic and cytotoxic effects of commercial formulation of alpha-cypermethrin in peripheral blood lymphocytes.

  7. Comparative study of the hepatotoxic, genotoxic and carcinogenic effects of praziquantel distocide & the natural myrrh extract Mirazid on adult male albino rats.

    PubMed

    Omar, Ahmed; Elmesallamy, Ghada El-Said; Eassa, Shereen

    2005-04-01

    Praziquantel (PZQ) is widely and effectively used in the control of bilharziasis which constitutes a major endemic health problem in Egypt. However, recent studies recommended that the drug must be re-evaluated because of its potential carcinogenicity and genotoxicity. Mirazid is a new natural anti-schistosomal drug formed of myrrh extract and considered to be a safe drug. This work was conducted to evaluate and compare hepatotoxic, genotoxic and carcinogenic effects of PZQ and Mirazid on adult male albino rats by assessment of serum levels of ALT, AST and bilirubin, histopathological study of the liver and cytogenetic study of bone marrow cells. 100 adult male albino rats were equally divided into 4 groups: (I): negative control, (II): control rats received distilled water, (III): received weekly single oral dose of PZQ (1500 mg/kg) for 6 weeks, (IV): received daily oral dose of Mirazid (500 mg/kg) for 6 weeks. At the end of the study 10 rats of each group were investigated by assessment of the levels of AST, ALT, & Bilirubin. After scarification, liver sections were examined by light microscopy. Another 10 rats of each group were submitted to cytogenetic examination. It was found that praziquantel induced a significant increase in the mean values of AST, ALT and bilirubin with areas of hyaline degeneration, fatty changes, dysplasia and necrosis in the liver sections. It also induced a significant increase in the incidence of chromosomal aberrations as polyploidy, fragment, deletion and ring chromosome as compared with control group. Mirazid induced a non significant increase in the mean values of AST, ALT and bilirubin, with a normal hepatic tissue, and a non significant increase in the incidence of chromosomal aberrations, as compared with the control group. On comparing both drugs, praziquantel induced a significant hepatotoxic, genotoxic and carcinogenic effects. It was concluded that, Praziquantel is considered to be a hepatotoxic, genotoxic and carcinogenic

  8. Effects of light on the cytotoxicity and genotoxicity of benzo(a)pyrene and an oil refinery effluent in the newt

    SciTech Connect

    Fernandez, M.; l`Haridon, J.

    1994-12-31

    The genotoxicity and/or toxicity of benzo(a)pyrene (BaP) were evaluated under different lighting conditions in larvae and embryos of the newt Pleurodeles waltl. Visible light alone, UVA alone, or BaP alone had no toxic effects on the larvae. Conversely, toxic effects were observed in animals exposed to BaP + daylight, or BaP + UVA. The genotoxicity of BaP (50 ppb) was halved by its previous exposure to UVA, and was abolished at the lowest concentration (12.5 ppb). In other experiments, the larvae were exposed alternatively to BaP or Irr BaP (18 hours in dark) and UVA (6 hr in water), every day for 8 days. All animals that had accumulated non-irradiated BaP (50 ppb) showed signs of severe toxicity, and 90% died before the end of the test. On the other hand, irradiated BaP (50 ppb) was a 4-fold less toxic and half as genotoxic as non-irradiated BaP. In addition, exposure of the animals to UVA alone for 4 days prior to treatment with BaP did not affect the genotoxicity or toxicity of this hydrocarbon. In the dark, the embryotoxicity of BaP was markedly attenuated by the presence of the jelly coats. Although UVA alone did not affect growth of the embryos, the toxicity of BaP was enhanced by the combined action of the two agents together or in succession (BaP + UVA or BaP then UVA). Larvae were treated with an oil refinery effluent (EF). At 125 ml/l, EF was not found to be genotoxic in the dark. However, in animals exposed to both EF and UVA, there was a progressive increase in level of micronucleated erythrocytes with increasing duration of daily exposure to UVA. Moreover, the genotoxic potential of irradiated EF + UVA was systematically below that of non-irradiated EF + UVA for all durations of exposure to ultraviolet light. Irradiation of this type of effluent might help reduce its harmful effects on aquatic species. Our results also suggest that metabolic activation is not necessary for hydrocarbons to induce toxic effects. 51 refs., 5 tabs., 3 figs.

  9. The effect of gamma radiation on the Common carp (Cyprinus carpio): In vivo genotoxicity assessment with the micronucleus and comet assays.

    PubMed

    M K, Praveen Kumar; Soorambail K, Shyama; Bhagatsingh Harisingh, Sonaye; D'costa, Avelyno; Ramesh Chandra, Chaubey

    2015-10-01

    Radioactive wastes may be leached into freshwater, either accidentally or in industrial effluents. We have studied gamma radiation-induced DNA damage in the freshwater fish Cyprinus carpio. Fish were irradiated with 2-10Gy gamma radiation and genotoxic effects in blood cells were studied with the micronucleus (MN) and comet assays. Micronuclei and a dose-dependent increase in comet-tail DNA were seen in dose- and time-dependent studies. The highest % tail DNA was observed at 24h, declining until 72h, which may indicate the repair of radiation-induced DNA single-strand breaks after gamma radiation. However, double-stranded DNA damage may not have been repaired, as indicated by increased micronuclei at later periods. A positive correlation was observed between the comet and micronucleus assay results. This study confirms the mutagenic/genotoxic potential of gamma radiation in the Common carp, as well as the possible combined use of the micronucleus and comet assays for in vivo laboratory studies with fresh-water fish for screening the genotoxic potential of radioactive pollution. PMID:26433258

  10. Genotoxicity and Cytotoxicity Evaluation of the Neolignan Analogue 2-(4-Nitrophenoxy)-1Phenylethanone and its Protective Effect Against DNA Damage

    PubMed Central

    Hanusch, Alex Lucas; de Oliveira, Guilherme Roberto; de Sabóia-Morais, Simone Maria Teixeira; Machado, Rafael Cosme; dos Anjos, Murilo Machado; Chen Chen, Lee

    2015-01-01

    Neolignans are secondary metabolites found in various groups of Angiosperms. They belong to a class of natural compounds with great diversity of chemical structures and pharmacological activities. These compounds are formed by linking two phenylpropanoid units. Several compounds that have ability to prevent genetic damage have been isolated from plants, and can be used to prevent or delay the development of tumor cells. Genetic toxicology evaluation is widely used in risk assessment of new drugs in preclinical screening tests. In this study, we evaluated the genotoxicity and cytotoxicity of the neolignan analogue 2-(4-nitrophenoxy)-1-phenylethanone (4NF) and its protective effect against DNA damage using the mouse bone marrow micronucleus test and the comet assay in mouse peripheral blood. Our results showed that this neolignan analogue had no genotoxic activity and was able to reduce induced damage both in mouse bone marrow and peripheral blood. Although the neolignan analogue 4NF was cytotoxic, it reduced cyclophosphamide-induced cytotoxicity. In conclusion, it showed no genotoxic action, but exhibited cytotoxic, antigenotoxic, and anticytotoxic activities. PMID:26554835

  11. [Research Progress in Genotoxic Effects of Degradation Products, Cobalt, Chromium Ions and Nanoparticles from Metal-on-metal Prostheses on Cells].

    PubMed

    Zhou, Hao; Han, Qinglin; Liu, Fan

    2015-04-01

    Cobalt or chromium alloys are the most common clinical materials of prosthesis and there have been some investigators at home and abroad have done related researches about the genotoxic effects of cobalt and chromium ions and nanoparticles. People have certain understanding about the mechanism of production of ions as well as their influence on cells. However, chromium or cobalt nanoparticles genotoxicity related research is still in its preliminary stage. In each stage, the mechanisms, from creating of the particles, through entering cells, until finally causing genotoxic, are still contained many problems to be solved. This article reviews the research progress in mechanisms of production and genotoxic effects of cobalt, chromium ions and nanoparticles.

  12. Long-term exposure to cypermethrin and piperonyl butoxide cause liver and kidney inflammation and induce genotoxicity in New Zealand white male rabbits.

    PubMed

    Vardavas, Alexander I; Stivaktakis, Polychronis D; Tzatzarakis, Manolis N; Fragkiadaki, Persefoni; Vasilaki, Fotini; Tzardi, Maria; Datseri, Galateia; Tsiaoussis, John; Alegakis, Athanasios K; Tsitsimpikou, Christina; Rakitskii, Valerii N; Carvalho, Félix; Tsatsakis, Aristidis M

    2016-08-01

    Cypermethrin (CY) is a frequently used class II pyrethroid pesticide, while piperonyl butoxide (PBO) plays a major role in the pesticide formulation of synthetic pyrethroids. Synthetic pyrethroids are metabolized in mammals via oxidation and ester hydrolysis. PBO can prevent the metabolism of CY and enhances its pesticide effect. While this potentiation effect reduces the amount of pesticide required to eliminate insects, it is not clear how this mixture affects mammals. In our in vivo experiment, New Zealand white male rabbits were exposed to low and high doses of CY, PBO, and their combinations, for 4 months. Genotoxicity and cytotoxicity were monitored by measuring binucleated cells with micronuclei (BNMN), micronuclei (MN) and the cytokinesis block proliferation index (CBPI) in lymphocytes. After two months of exposure, a statistically significant increase in the frequency of BNMN was observed for all exposed animals (p < 0.001) in a dose-dependent way. MN were significantly elevated compared to controls (p < 0.001), with high dose groups reaching a 442% increase when co-exposed. BNMN and MN continued to increase after four months. Histopathological examination of lesions showed damage involving inflammation, attaining lymphoplasmatocytic infiltration in the high dose groups. Both CY and PBO cause liver and kidney inflammation and induce genotoxicity. PMID:27321377

  13. High-throughput genotoxicity assay identifies antioxidants as inducers of DNA damage response and cell death

    EPA Science Inventory

    Human ATAD5 is an excellent biomarker for identifying genotoxic compounds because ATADS protein levels increase post-transcriptionally following exposure to a variety of DNA damaging agents. Here we report a novel quantitative high-throughput ATAD5-Iuciferase assay that can moni...

  14. Genotoxic effects in occupational exposure to formaldehyde: A study in anatomy and pathology laboratories and formaldehyde-resins production

    PubMed Central

    2010-01-01

    Background According to the Report on Carcinogens, formaldehyde ranks 25th in the overall U.S. chemical production, with more than 5 million tons produced each year. Given its economic importance and widespread use, many people are exposed to formaldehyde environmentally and/or occupationally. Presently, the International Agency for Research on Cancer classifies formaldehyde as carcinogenic to humans (Group 1), based on sufficient evidence in humans and in experimental animals. Manyfold in vitro studies clearly indicated that formaldehyde can induce genotoxic effects in proliferating cultured mammalian cells. Furthermore, some in vivo studies have found changes in epithelial cells and in peripheral blood lymphocytes related to formaldehyde exposure. Methods A study was carried out in Portugal, using 80 workers occupationally exposed to formaldehyde vapours: 30 workers from formaldehyde and formaldehyde-based resins production factory and 50 from 10 pathology and anatomy laboratories. A control group of 85 non-exposed subjects was considered. Exposure assessment was performed by applying simultaneously two techniques of air monitoring: NIOSH Method 2541 and Photo Ionization Detection equipment with simultaneously video recording. Evaluation of genotoxic effects was performed by application of micronucleus test in exfoliated epithelial cells from buccal mucosa and peripheral blood lymphocytes. Results Time-weighted average concentrations not exceeded the reference value (0.75 ppm) in the two occupational settings studied. Ceiling concentrations, on the other hand, were higher than reference value (0.3 ppm) in both. The frequency of micronucleus in peripheral blood lymphocytes and in epithelial cells was significantly higher in both exposed groups than in the control group (p < 0.001). Moreover, the frequency of micronucleus in peripheral blood lymphocytes was significantly higher in the laboratories group than in the factory workers (p < 0.05). A moderate positive

  15. Cytogenetic and genotoxic effects of zinc oxide nanoparticles on root cells of Allium cepa.

    PubMed

    Kumari, Mamta; Khan, S Sudheer; Pakrashi, Sunandan; Mukherjee, Amitava; Chandrasekaran, Natarajan

    2011-06-15

    Increasing use of zinc oxide nanoparticles (ZnO NP) in consumer products may enhance its release into the environment. Phytotoxicity study is important to understand its possible environmental impact. Allium cepa (Onion bulb) is the best model organism to study genetic toxicology of nanoparticles. Here we have reported cytogenetic and genotoxic effects of ZnO NPs on the root cells of A. cepa. The effects of ZnO NPs on the mitotic index (MI), micronuclei index (MN index), chromosomal aberration index, and lipid peroxidation were determined through the hydroponic culturing of A. cepa. A. cepa roots were treated with the dispersions of ZnO NPs at four different concentrations (25, 50, 75, and 100 μg ml(-1)). With the increasing concentrations of ZnO NPs MI decreased with the increase of pycnotic cells, on the other hand MN and chromosomal aberration index increased. The frequency of micronucleated cells was higher in ZnO NPs treated cells as compared to control (deionized distilled water). The number of cells in each mitotic phase changed upon ZnO NPs treatment. The effect of ZnO NPs on lipid peroxidation as examined by measuring TBARS concentration was evident at all the concentrations compared to bulk ZnO. The TEM image showed internalization of ZnO NPs like particles. SEM image of treated A. cepa demonstrated that the internalized nanoparticles agglomerated depending on the physico-chemical environment inside the cell. Our results demonstrated that ZnO NPs can be a clastogenic/genotoxic and cytotoxic agent. In conclusion, the A. cepa cytogenetic test can be used for the genotoxicity monitoring of novel nanomaterials like ZnO NPs, which is used in many consumer products.

  16. Synergistic and antagonistic effects on genotoxicity of chemicals commonly found in hazardous waste sites

    SciTech Connect

    Ma, T.H.; Sandhu, S.S.; Peng, Y.; Chen, T.D.; Kim, T.W.

    1992-01-01

    Synergistic and antagonistic effects on genotoxicity of mixtures of four chemicals; i.e., lead tetraacetate (LTA), arsenic trioxide (ATO), dieldrin (DED), and tetrachloroethylene (TCE), were evaluated by the Tradescantia-micronucleus (Trad-MCN) assay. The chemicals were mixed in ratios of 1:1, 1:2 and 2:1 for mixtures of two chemicals and 1:1:1 each for three chemicals. The concentration of stock solution of these chemicals was around the minimum effective dose (MED) or below the MED for these chemicals as reported by Sandhu et al. (1989). Treatments were applied to plant cuttings by hydroponic uptake of the mixed solutions through the stems of the plant for 30 h followed by fixation of the flower buds in aceto-alcohol (1:3 ratio) without a recovery period. Microslides were prepared for scoring MCN frequencies. Results of two series of repeated experiments indicated that all mixtures of LTA/ATO exhibited antagonistic effects. On the other hand, all mixtures of TCE and DED exhibited synergistic effect. These data indicate that for evaluating biological hazards at chemical waste sites, it is prudent to evaluate the genotoxicity of complex chemical mixtures as these exist in nature because the biological effects based on evaluating individual chemicals may not be true predictors of the interactive effects of the pollutants.

  17. Lack of genotoxic effect of food dyes amaranth, sunset yellow and tartrazine and their metabolites in the gut micronucleus assay in mice.

    PubMed

    Poul, Martine; Jarry, Gérard; Elhkim, Mostafa Ould; Poul, Jean-Michel

    2009-02-01

    The food dyes amaranth, sunset yellow and tartrazine were administered twice, at 24h intervals, by oral gavage to mice and assessed in the in vivo gut micronucleus test for genotoxic effects (frequency of micronucleated cells) and toxicity (apoptotic and mitotic cells). The concentrations of each compound and their main metabolites (sulfanilic acid and naphthionic acid) were measured in faeces during a 24-h period after single oral administrations of the food dyes to mice. Parent dye compounds and their main aromatic amine metabolites were detected in significant amounts in the environment of colonic cells. Acute oral exposure to food dye additives amaranth, sunset yellow and tartrazine did not induce genotoxic effect in the micronucleus gut assay in mice at doses up to 2000 mg/kg b.w. Food dyes administration increased the mitotic cells at all dose levels when compared to controls. These results suggest that the transient DNA damages previously observed in the colon of mice treated by amaranth and tartrazine by the in vivo comet assay [Sasaki, Y.F., Kawaguchi, S., Kamaya, A., Ohshita, M., Kabasawa, K., Iwama, K., Taniguchi, K., Tsuda, S., 2002. The comet assay with 8 mouse organs: results with 39 currently used food additives. Mutat. Res. 519, 103-119] are unable to be fixed in stable genotoxic lesions and might be partly explained by local cytotoxicity of the dyes.

  18. The genotoxic effects of the imidacloprid-based insecticide formulation Glacoxan Imida on Montevideo tree frog Hypsiboas pulchellus tadpoles (Anura, Hylidae).

    PubMed

    Pérez-Iglesias, J M; Ruiz de Arcaute, C; Nikoloff, N; Dury, L; Soloneski, S; Natale, G S; Larramendy, M L

    2014-06-01

    The neonicotinoid insecticide imidacloprid (IMI) affects the insect central nervous system and is successfully applied to control pests for a variety of agricultural crops. In the current study, acute toxicity and genotoxicity of the IMI-containing commercial formulation insecticide Glacoxan Imida (35 percent IMI) was evaluated on Hypsiboas pulchellus (Anura: Hylidae) tadpoles exposed under laboratory conditions. A lethal effect was evaluated as the end point for lethality, whereas micronucleus (MN) frequency and DNA single-strand breaks evaluated by the single cell gel electrophoresis (SCGE) assay were employed as end points for genotoxicity. Sublethal end points were assayed within the 12.5-37.5mg/L IMI concentration range. Experiments were performed on tadpoles at stage 36 (range, 35-37) according to the classification proposed by Gosner. Lethality studies revealed an LC50 96h value of 52.622mg/L IMI. Increased frequency of MNs was only observed when 25.0mg/L was assayed for 96h, whereas no other nuclear abnormalities were induced. Increase of the genetic damage index was observed at 48h of treatment within the 12.5-37.5mg/L concentration range, whereas an increased frequency of DNA damage was observed only in tadpoles treated with 37.5mg/L IMI for 96h. This study represents the first evidence of the acute lethal and genotoxic effects exerted by IMI on tadpoles of an amphibian species native to Argentina under laboratory conditions.

  19. Genotoxic effects of deoxynivalenol in broiler chickens fed low-protein feeds.

    PubMed

    Awad, W A; Ghareeb, K; Dadak, A; Gille, L; Staniek, K; Hess, M; Böhm, J

    2012-03-01

    Deoxynivalenol (DON) is one of the most abundant and important trichothecenes in food and feed, and it is a significant contaminant due to its frequent occurrence at toxicologically relevant concentrations worldwide. Deoxynivalenol has negative influences on the health and performance of chicks. However, there is little information available regarding the effect of DON on DNA fragmentation in blood lymphocytes. In addition, the effects of Mycofix select (Biomin GmbH, Herzogenburg, Austria) supplementation to DON-contaminated broiler diets on lymphocyte DNA have not yet been demonstrated. Therefore, the aim of the present study was to establish the effect of DON on lipid peroxidation and lymphocyte DNA fragmentation in broilers and to evaluate the potential of Mycofix select in the prevention of toxin-mediated changes. Thirty-two 1-d-old (Ross 308 male) broiler chicks were randomly divided into 4 groups. The control group was fed a noncontaminated diet, and a second group was fed the same diet but supplemented with Mycofix select (0.25%). A third group of broilers was fed a diet artificially contaminated with 10 mg of feed-grade DON/kg of diet, and a fourth group was fed a DON-contaminated diet supplemented with Mycofix select. At the end of the feeding trial, blood was collected and the degree of lymphocyte DNA damage was measured in the plasma by comet assay. Deoxynivalenol increased (P = 0.016) the amount of DNA damage in chicken lymphocytes by 46.8%. Mycofix select protected lymphocyte DNA from the DON effects. To our knowledge, these are the first data on genotoxic effects of a moderate dose of DON on chicken lymphocytes. However, the thiobarbituric acid reactive substances level in liver and liver enzyme activity did not differ among the groups. In conclusion, the present study demonstrated that the diets contaminated with the mycotoxin DON at moderate levels in combination with low-protein feed are able to induce lymphocyte DNA damage in chickens

  20. Antiproliferative and genotoxic effects of nature identical and artificial synthetic food additives of aroma and flavor.

    PubMed

    Nunes, R D M; Sales, I M S; Silva, S I O; Sousa, J M C; Peron, A P

    2016-07-25

    This study aimed to analyze the antiproliferative and genotoxic potential of synthetic food flavorings, nature identical passion fruit and artificial vanilla. This assessment used root meristem cells of Allium cepa L., in exposure times of 24 and 48 hours and using doses of 0.2; 0.4 and 0.6 mL. Roots were fixed in Carnoy's solution, hydrolyzed in hydrochloric acid, stained with acetic orcein and analyzed with optical microscope at 400× magnification, 5,000 cells for each treatment. For data analysis, it was used Chi-square test at 5%. Doses of 0.2 mL at ET 48 h; 0.4 and 0.6 mL at ET 24 and 48 h of passion fruit flavor, and the three doses of the vanilla flavor at ET 24 and 48 h significantly reduced the cell division rate in the meristems of roots, proving to be cytotoxic. Doses of 0.2; 0.4 and 0.6 mL of the passion fruit additive, and the three doses of vanilla tested, in the two exposure times, induced mitotic spindle changes and micronuclei formation in the cells of the test organism used, proving to be genotoxic. Therefore, under the studied conditions, flavoring solutions of vanilla and passion fruit, marketed nationally and internationally, significantly altered the functioning of the cell cycle in root meristem cells of A. cepa.

  1. Antiproliferative and genotoxic effects of nature identical and artificial synthetic food additives of aroma and flavor.

    PubMed

    Nunes, R D M; Sales, I M S; Silva, S I O; Sousa, J M C; Peron, A P

    2016-07-25

    This study aimed to analyze the antiproliferative and genotoxic potential of synthetic food flavorings, nature identical passion fruit and artificial vanilla. This assessment used root meristem cells of Allium cepa L., in exposure times of 24 and 48 hours and using doses of 0.2; 0.4 and 0.6 mL. Roots were fixed in Carnoy's solution, hydrolyzed in hydrochloric acid, stained with acetic orcein and analyzed with optical microscope at 400× magnification, 5,000 cells for each treatment. For data analysis, it was used Chi-square test at 5%. Doses of 0.2 mL at ET 48 h; 0.4 and 0.6 mL at ET 24 and 48 h of passion fruit flavor, and the three doses of the vanilla flavor at ET 24 and 48 h significantly reduced the cell division rate in the meristems of roots, proving to be cytotoxic. Doses of 0.2; 0.4 and 0.6 mL of the passion fruit additive, and the three doses of vanilla tested, in the two exposure times, induced mitotic spindle changes and micronuclei formation in the cells of the test organism used, proving to be genotoxic. Therefore, under the studied conditions, flavoring solutions of vanilla and passion fruit, marketed nationally and internationally, significantly altered the functioning of the cell cycle in root meristem cells of A. cepa. PMID:27463833

  2. Genotoxic effects and induction of phytochelatins in the presence of cadmium in Vicia faba roots.

    PubMed

    Béraud, Eric; Cotelle, Sylvie; Leroy, Pierre; Férard, Jean-François

    2007-10-01

    This study investigates different effects in roots of Vicia faba (broad bean) after exposure to cadmium. Genotoxic effects were assessed by use of the well-known Vicia root tip micronucleus assay. Cytotoxic effects were evaluated by determining the mitotic index in root tip cells. Finally, molecular induction mechanisms were evaluated by measuring phytochelatins with HPLC. After hydroponical exposure of V. faba roots to a range of cadmium concentrations and during different exposure times, the results of this approach showed large variations, according to the endpoint measured: after 48 h of exposure, genotoxic effects were found between 7.5 x 10(-8) and 5 x 10(-7)M CdCl(2), and cytotoxic effects were observed between 2.5 x 10(-7) and 5 x 10(-7)M CdCl(2). Statistically significant phytochelatin (PC) concentrations were measured at >or=10(-6)M CdCl(2) for PC(2), and at >or=10(-5)M CdCl(2) for PC3 and PC4. PMID:17689137

  3. Genotoxic effects and induction of phytochelatins in the presence of cadmium in Vicia faba roots.

    PubMed

    Béraud, Eric; Cotelle, Sylvie; Leroy, Pierre; Férard, Jean-François

    2007-10-01

    This study investigates different effects in roots of Vicia faba (broad bean) after exposure to cadmium. Genotoxic effects were assessed by use of the well-known Vicia root tip micronucleus assay. Cytotoxic effects were evaluated by determining the mitotic index in root tip cells. Finally, molecular induction mechanisms were evaluated by measuring phytochelatins with HPLC. After hydroponical exposure of V. faba roots to a range of cadmium concentrations and during different exposure times, the results of this approach showed large variations, according to the endpoint measured: after 48 h of exposure, genotoxic effects were found between 7.5 x 10(-8) and 5 x 10(-7)M CdCl(2), and cytotoxic effects were observed between 2.5 x 10(-7) and 5 x 10(-7)M CdCl(2). Statistically significant phytochelatin (PC) concentrations were measured at >or=10(-6)M CdCl(2) for PC(2), and at >or=10(-5)M CdCl(2) for PC3 and PC4.

  4. Integrated analysis of the ecotoxicological and genotoxic effects of the antimicrobial peptide melittin on Daphnia magna and Pseudokirchneriella subcapitata.

    PubMed

    Galdiero, Emilia; Maselli, Valeria; Falanga, Annarita; Gesuele, Renato; Galdiero, Stefania; Fulgione, Domenico; Guida, Marco

    2015-08-01

    Melittin is a major constituent of the bee venom of Apis mellifera with a broad spectrum of activities. Melittin therapeutical potential is subject to its toxicity and the assessment of ecotoxicity and genotoxicity is of particular interest for therapeutic use. Here we analyzed the biological effects of melittin on two aquatic species, which are representative of two different levels of the aquatic trophic chain: the invertebrate Daphnia magna and the unicellular microalgae Pseudokirchneriella subcapitata. The attention was focused on the determination of: i) ecotoxicity; ii) genotoxicity; iii) antigenotoxicity. Our main finding is that melittin is detrimental to D. magna reproduction and its sub-lethal concentrations create an accumulation dependent on exposition times and a negative effect on DNA. We also observed that melittin significantly delayed time to first eggs. Moreover, results showed that melittin exerted its toxic and genotoxic effects in both species, being a bit more aggressive towards P. subcapitata.

  5. Determination of genotoxic effects of boron and zinc on Zea mays using protein and random amplification of polymorphic DNA analyses.

    PubMed

    Erturk, Filiz Aygun; Nardemir, Gokce; Hilal, A Y; Arslan, Esra; Agar, Guleray

    2015-11-01

    In this research, we aimed to determine genotoxic effects of boron (B) and zinc (Zn) on Zea mays by using total soluble protein content and random amplification of polymorphic DNA (RAPD) analyses. For the RAPD analysis, 16 RAPD primers were found to produce unique polymorphic band profiles on treated maize seedlings. With increased Zn and B concentrations, increased polymorphism rate was observed, while genomic template stability and total soluble protein content decreased. The treatment with Zn was more effective than that of B groups on the levels of total proteins. The obtained results from this study revealed that the total soluble protein levels and RAPD profiles were performed as endpoints of genotoxicity and these analyses can offer useful biomarker assays for the evaluation of genotoxic effects on Zn and B polluted plants.

  6. Integrated analysis of the ecotoxicological and genotoxic effects of the antimicrobial peptide melittin on Daphnia magna and Pseudokirchneriella subcapitata.

    PubMed

    Galdiero, Emilia; Maselli, Valeria; Falanga, Annarita; Gesuele, Renato; Galdiero, Stefania; Fulgione, Domenico; Guida, Marco

    2015-08-01

    Melittin is a major constituent of the bee venom of Apis mellifera with a broad spectrum of activities. Melittin therapeutical potential is subject to its toxicity and the assessment of ecotoxicity and genotoxicity is of particular interest for therapeutic use. Here we analyzed the biological effects of melittin on two aquatic species, which are representative of two different levels of the aquatic trophic chain: the invertebrate Daphnia magna and the unicellular microalgae Pseudokirchneriella subcapitata. The attention was focused on the determination of: i) ecotoxicity; ii) genotoxicity; iii) antigenotoxicity. Our main finding is that melittin is detrimental to D. magna reproduction and its sub-lethal concentrations create an accumulation dependent on exposition times and a negative effect on DNA. We also observed that melittin significantly delayed time to first eggs. Moreover, results showed that melittin exerted its toxic and genotoxic effects in both species, being a bit more aggressive towards P. subcapitata. PMID:25884346

  7. CDC42 Gtpase Activation Affects Hela Cell DNA Repair and Proliferation Following UV Radiation-Induced Genotoxic Stress.

    PubMed

    Ascer, Liv G; Magalhaes, Yuli T; Espinha, Gisele; Osaki, Juliana H; Souza, Renan C; Forti, Fabio L

    2015-09-01

    Cell division control protein 42 (CDC42) homolog is a small Rho GTPase enzyme that participates in such processes as cell cycle progression, migration, polarity, adhesion, and transcription. Recent studies suggest that CDC42 is a potent tumor suppressor in different tissues and is related to aging processes. Although DNA damage is crucial in aging, a potential role for CDC42 in genotoxic stress remains to be explored. Migration, survival/proliferation and DNA damage/repair experiments were performed to demonstrate CDC42 involvement in the recovery of HeLa cells exposed to ultraviolet radiation-induced stress. Sub-lines of HeLa cells ectopically expressing the constitutively active CDC42-V12 mutant were generated to examine whether different CDC42-GTP backgrounds might reflect different sensitivities to UV radiation. Our results show that CDC42 constitutive activation does not interfere with HeLa cell migration after UV radiation. However, the minor DNA damage exhibited by the CDC42-V12 mutant exposed to UV radiation most likely results in cell cycle arrest at the G2/M checkpoint and reduced proliferation and survival. HeLa cells and Mock clones, which express endogenous wild-type CDC42 and show normal activity, are more resistant to UV radiation. None of these effects are altered by pharmacological CDC42 inhibition. Finally, the phosphorylation status of the DNA damage response proteins γ-H2AX and p-Chk1 was found to be delayed and attenuated, respectively, in CDC42-V12 clones. In conclusion, the sensitivity of HeLa cells to ultraviolet radiation increases with CDC42 over-activation due to inadequate DNA repair signaling, culminating in G2/M cell accumulation, which is translated into reduced cellular proliferation and survival.

  8. Estimation of TiO₂ nanoparticle-induced genotoxicity persistence and possible chronic gastritis-induction in mice.

    PubMed

    Mohamed, Hanan Ramadan Hamad

    2015-09-01

    Titanium dioxide (TiO2) nanoparticles are widely used as a food additive and coloring agent in many consumer products however limited data is available on the nano-TiO2 induced genotoxicity persistence. Thus, this study investigated the persistence of nano-TiO2 induced genotoxicity and possible induction of chronic gastritis in mice. The mice were orally administered 5, 50 or 500 mg/kg body weight nano-TiO2 for five consecutive days, and then mice from each dosage group were sacrificed 24 h or one or two weeks after the last treatment. The administration of nano-TiO2 resulted in persistent apoptotic DNA fragmentation and mutations in p53 exons (5-8) as well as significant persistent elevations in malondialdehyde and nitric oxide levels and decreases in the reduced glutathione level and catalase activity compared with the control mice in a dose- and time-dependent manner. Necrosis and inflammation were evident upon histological examination. These findings could be attributed to the persistent accumulation of nano-TiO2 at the tested doses at all three time points. Based on these findings, we conclude that the administration of nano-TiO2, even at low doses, leads to persistent accumulation of nano-TiO2 in mice, resulting in persistent inflammation, apoptosis and oxidative stress, ultimately leading to the induction of chronic gastritis.

  9. In vitro evaluation of the cytotoxic and genotoxic effects of artemether, an antimalarial drug, in a gastric cancer cell line (PG100).

    PubMed

    Alcântara, Diego Di Felipe Ávila; Ribeiro, Helem Ferreira; Cardoso, Plínio Cerqueira Dos Santos; Araújo, Taíssa Maíra Thomaz; Burbano, Rommel Rodriguez; Guimarães, Adriana Costa; Khayat, André Salim; de Oliveira Bahia, Marcelo

    2013-02-01

    Artemisinin is a sesquiterpene lactone endoperoxide, obtained from Artemisia annua, and extensively used as an antimalarial drug. Many studies have reported the genotoxic and cytotoxic effects of artemisinins; however, there are no studies that compare such effects between cancer cell lines and normal human cells after treatment with artemether, an artemisinin derivative. Gastric cancer is the fourth most frequent type of cancer and the second highest cause of cancer mortality worldwide. Thus, the aim of this study was to evaluate the in vitro genotoxic and cytotoxic effects induced by artemether in gastric cancer cell line (PG100) and compare them with the results obtained in human lymphocytes exposed to the same conditions. We used MTT (3-(4,5-methylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide) assay, comet assay and ethidium bromide/acridine orange viability staining to evaluate the cytotoxic and genotoxic effects of artemether in PG100. MTT assay showed a decrease in the survival percentages for both cell types treated with different concentrations of artemether (P < 0.05). PG100 also showed a significant dose-dependent increase in DNA damage index at concentrations of 119.4 and 238.8 µg ml(-1) (P < 0.05). Our results showed that artemether induced necrosis in PG100 at concentrations of 238.8 and 477.6 µg ml(-1), for all the tested harvest times (P < 0.05). In lymphocytes, artemether induced both apoptosis and necrosis at concentrations of 238.8 and 477.6 µg ml(-1), for all the tested harvest times (P < 0.05). In conclusion, human lymphocytes were more sensitive to the cytotoxic effects of the antimalarial drug than the gastric cancer cell line PG100. PMID:21953315

  10. Benzophenone guttiferone A from Garcinia achachairu Rusby (Clusiaceae) Presents Genotoxic Effects in Different Cells of Mice

    PubMed Central

    Terrazas, Peterson Menezes; de Souza Marques, Eduardo; Mariano, Luisa Nathália Bolda; Cechinel-Filho, Valdir; Niero, Rivaldo; Andrade, Sergio Faloni; Maistro, Edson Luis

    2013-01-01

    Benzophenones from natural sources and those of synthetic analogues present several reports of potent biological properties, and Guttiferone A represents a promising medicinal natural compound with analgesic and gastroprotective profiles. Considering that there are no reports that assess the genetic toxicity of Guttiferone A, the present study was undertaken to investigate the genotoxic potential of this benzophenone isolated from seeds of Garcinia achachairu in terms of DNA damage in different cells of Swiss albino mice using the comet assay, and its clastogenic/aneugenic effects in bone marrow cells in vivo by the micronucleus test. Cytotoxicity was assessed by scoring polychromatic (PCE) and normochromatic (NCE) erythrocytes ratio. Guttiferone A was administered by oral gavage at doses of 15, 30 and 60 mg/kg. The results showed that Guttiferone A produced genotoxic effects in leukocytes, liver, bone marrow, brain and testicle cells and clastogenic/aneugenic effects in bone marrow erythrocytes of mice. The PCE/NCE ratio indicated no cytotoxicity. Since guttiferone A is harmful to the genetic material we suggest caution in its use by humans. PMID:24250785

  11. [Genotoxic effects of pesticide-treated vegetable extracts using the Allium cepa chromosome aberration and micronucleus tests].

    PubMed

    Biscardi, D; De Fusco, R; Feretti, D; Zerbini, I; Izzo, C; Esposito, V; Nardi, G; Monarca, S

    2003-01-01

    The presence of chemical residues in vegetables and fruit is a source of human exposure to toxic and genotoxic chemicals. The mutagenic and carcinogenic action of herbicides, insecticides and fungicides on experimental animals is already known. Several studies have shown that chronic exposure to low levels of pesticides can cause adverse health effects and that many pesticides are mutagenic/carcinogenic. In the present research we monitored concurrently the presence of pesticides and genotoxic compounds extracted from 21 treated vegetables and 8 types of grapes sampled from the markets of a region in Southern Italy. The extracts were analysed for pesticides by gas-chromatography and HPLC, and for genotoxicity with two plant tests in Allium cepa roots: the micronucleus test and the chromosomal aberration test. We found 33 pesticides, some of which are outlawed. Genotoxicity was found in some of the vegetables and grapes tested. Allium cepa tests were sensitive for monitoring genotoxicity in food extracts. The micronucleus test in interphase cells gave much higher mutagenicity than the chromosomal aberration test in anaphase-telophase cells. PMID:15049565

  12. Assessment of genotoxic effects of lead in occupationally exposed workers.

    PubMed

    Chinde, Srinivas; Kumari, Monika; Devi, Kanapuram Rudrama; Murty, Upadhyayula Suryanarayana; Rahman, Mohammed Fazlur; Kumari, Srinivas Indu; Mahboob, Mohammed; Grover, Paramjit

    2014-10-01

    The genotoxicological effects in 200 lead acid storage battery recycling and manufacturing industry workers in Hyderabad along with matched 200 controls were studied. The genetic damage was determined by comet, micronucleus (MN), and chromosomal aberration (CA) test in peripheral blood lymphocytes (PBL). The MN test was also carried out in buccal epithelial cells (BECs). Pb in ambient air, blood Pb (B-Pb) concentrations, and hematological parameters were measured. The superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), glutathione peroxidase (GPx), and malondialdehyde (MDA) formed were also studied. The results of the present study showed that there was a statistically significant (P < 0.01) increase in mean percent tail DNA, frequency of CA, and MN in PBL as well as in BEC as compared to controls. Pb in ambient air and B-Pb concentrations were found to be significantly higher (P < 0.01). The hematocrit, hemoglobin, and red blood cell values were significantly lowered in Pb-exposed workers in comparison to controls. SOD, GPx, and CAT levels were significantly decreased while GSH and MDA levels increased in exposed group when compared to control group. The present study suggests that environmental health standards should be enforced to control Pb contamination from battery industries to reduce human health risk.

  13. Genotoxic effect of cadmium in okra seedlings: comparative investigation with population parameters and molecular markers.

    PubMed

    Aydin, Semra Soydam; Basaran, Esin; Cansaran-Duman, Demet; Aras, Sümer

    2013-11-01

    Plants are considered as good bioindicators because of their significant role in food chain transfer. They are also easy to grow, adaptable to environmental stresses and can be used for assaying a range of environmental conditions in different habitats. Thus, many plant species have been used as bioindicators. In order to evaluate the genotoxic effect of cadmium, okra (Abelmoschus esculontus L.) seedlings were treated with different concentrations (30, 60, 120 mg I(-1)) of cadmium and investigated for their population parameters such as inhibition of root growth; total soluble protein content, dry weight and also the impact of metal on the genetic material by RAPD analysis. Root growth and total soluble protein content in okra seedlings were reduced with increased Cd concentrations. RAPD analysis indicated formation of new bands mostly at 60 and 120 mg I(-1) Cd treatments. Altered DNA band patterns and population parameters after Cd treatments suggest that okra could be used as an indicator to reveal the effects of genotoxic agents.

  14. Genotoxic effect of cadmium in okra seedlings: comparative investigation with population parameters and molecular markers.

    PubMed

    Aydin, Semra Soydam; Basaran, Esin; Cansaran-Duman, Demet; Aras, Sümer

    2013-11-01

    Plants are considered as good bioindicators because of their significant role in food chain transfer. They are also easy to grow, adaptable to environmental stresses and can be used for assaying a range of environmental conditions in different habitats. Thus, many plant species have been used as bioindicators. In order to evaluate the genotoxic effect of cadmium, okra (Abelmoschus esculontus L.) seedlings were treated with different concentrations (30, 60, 120 mg I(-1)) of cadmium and investigated for their population parameters such as inhibition of root growth; total soluble protein content, dry weight and also the impact of metal on the genetic material by RAPD analysis. Root growth and total soluble protein content in okra seedlings were reduced with increased Cd concentrations. RAPD analysis indicated formation of new bands mostly at 60 and 120 mg I(-1) Cd treatments. Altered DNA band patterns and population parameters after Cd treatments suggest that okra could be used as an indicator to reveal the effects of genotoxic agents. PMID:24555326

  15. Investigations on cytotoxic and genotoxic effects of laser printer emissions in human epithelial A549 lung cells using an air/liquid exposure system.

    PubMed

    Tang, Tao; Gminski, Richard; Könczöl, Mathias; Modest, Christoph; Armbruster, Benedikt; Mersch-Sundermann, Volker

    2012-03-01

    Exposure to emissions from laser printers during the printing process is commonplace worldwide, both in the home and workplace environment. In the present study, cytotoxic and genotoxic effects of the emission from five low to medium-throughput laser printers were investigated with respect to the release of ozone (O(3) ), volatile organic compounds (VOC), particulate matter (PM), and submicrometer particles (SMP) during standby and operation. Experiments were conducted in a 1 m(3) emission chamber connected to a Vitrocell® exposure system. Cytotoxicity was determined by the WST-1 assay and genotoxicity by the micronucleus test in human A549 lung cells. The five laser printers emitted varying but generally small amounts of O(3) , VOC, and PM. VOC emissions included 13 compounds with total VOC concentrations ranging from 95 to 280 μg/m(3) (e.g., 2-butanone, hexanal, m,p-xylene, and o-xylene). Mean PM concentrations were below 2.4 μg/m(3). SMP number concentration levels during standby ranged from 9 to 26 particles/cm(3). However, three of the printers generated a 90 to 16 × 10(3) -fold increase of SMP during the printing process (maximum 294,460 particles/cm(3)). Whereas none of the printer emissions were found to cause cytotoxicity, emissions from two printers induced formation of micronuclei (P < 0.001), thus providing evidence for genotoxicity. As yet, differences in biological activity cannot be explained on the basis of the specific emission characteristics of the different printers. Because laser printing technology is widely used, studies with additional cytogenetic endpoints are necessary to confirm the DNA-damaging potency and to identify emission components responsible for genotoxicity.

  16. In vivo systemic chlorogenic acid therapy under diabetic conditions: Wound healing effects and cytotoxicity/genotoxicity profile.

    PubMed

    Bagdas, Deniz; Etoz, Betul Cam; Gul, Zulfiye; Ziyanok, Sedef; Inan, Sevda; Turacozen, Ozge; Gul, Nihal Yasar; Topal, Ayse; Cinkilic, Nilufer; Tas, Sibel; Ozyigit, Musa Ozgur; Gurun, Mine Sibel

    2015-07-01

    Oxidative stress occurs following the impairment of pro-oxidant/antioxidant balance in chronic wounds and leads to harmful delays in healing progress. A fine balance between oxidative stress and endogenous antioxidant defense system may be beneficial for wound healing under redox control. This study tested the hypothesis that oxidative stress in wound area can be controlled with systemic antioxidant therapy and therefore wound healing can be accelerated. We used chlorogenic acid (CGA), a dietary antioxidant, in experimental diabetic wounds that are characterized by delayed healing. Additionally, we aimed to understand possible side effects of CGA on pivotal organs and bone marrow during therapy. Wounds were created on backs of streptozotocin-induced diabetic rats. CGA (50 mg/kg/day) was injected intraperitoneally. Animals were sacrificed on different days. Biochemical and histopathological examinations were performed. Side effects of chronic antioxidant treatment were tested. CGA accelerated wound healing, enhanced hydroxyproline content, decreased malondialdehyde/nitric oxide levels, elevated reduced-glutathione, and did not affect superoxide dismutase/catalase levels in wound bed. While CGA induced side effects such as cyto/genotoxicity, 15 days of treatment attenuated blood glucose levels. CGA decreased lipid peroxidation levels of main organs. This study provides a better understanding for antioxidant intake on diabetic wound repair and possible pro-oxidative effects.

  17. Genotoxic and cytotoxic effects of Sunset Yellow and Brilliant Blue, colorant food additives, on human blood lymphocytes.

    PubMed

    Kus, Esra; Eroglu, Halil Erhan

    2015-01-01

    The synthetic dyes over fifty are used in many areas including the food industry around the world. Sunset Yellow FCF and Brilliant Blue FCF are used as colorant food additives in many food products. The present study investigated the genotoxic and cytotoxic effects of Sunset Yellow and Brilliant Blue. Genotoxic and cytotoxic activities of the food additives were evaluated in lymphocyte cell cultures using mitotic index, replication index and micronucleus assay. Mitotic index frequencies and replication index values were decreased and micronucleus frequency was increased with increasing concentrations of Sunset Yellow and Brilliant Blue. The changes in mitotic index and micronucleus are statistically significant (p<0.05). The results show that the Sunset Yellow and Brilliant Blue can have cytotoxic and genotoxic potential. It care must be taken when using these materials as a food additive.

  18. Determination of the genotoxic effects of Convolvulus arvensis extracts on corn (Zea mays L.) seeds.

    PubMed

    Sunar, Serap; Yildirim, Nalan; Aksakal, Ozkan; Agar, Guleray

    2013-06-01

    In this research, the methanolic extracts of Convolvulus arvensis were tested for genotoxic and inhibitor activity on the total soluble protein content and the genomic template stability against corn Zea mays L. seed. The methanol extracts of leaf, stem and root of C. arvensis were diluted to 50, 75 and 100 μl concentrations and applied to corn seed. The total soluble protein and genomic template stability results were compared with the control. The results showed that especially 100 μl extracts of diluted leaf, stem and root had a strong inhibitory activity on the genomic template stability. The changes occurred in random amplification of polymorphic DNA (RAPD) profiles of C. arvensis extract treatment included variation in band intensity, loss of bands and appearance of new bands compared with control. Also, the results obtained from this study revealed that the increase in the concentrations of C. arvensis extract increased the total soluble protein content in maize. The results suggested that RAPD analysis and total protein analysis could be applied as a suitable biomarker assay for the detection of genotoxic effects of plant allelochemicals.

  19. Genotoxic biomonitoring of tobacco farmers: Biomarkers of exposure, of early biological effects and of susceptibility.

    PubMed

    Da Silva, Fernanda Rabaioli; Da Silva, Juliana; Allgayer, Mariangela da C; Simon, Caroline F; Dias, Johnny F; dos Santos, Carla E I; Salvador, Mirian; Branco, Catia; Schneider, Nayê Balzan; Kahl, Vivian; Rohr, Paula; Kvitko, Kátia

    2012-07-30

    Tobacco farming presents several hazards to those who cultivate and harvest the plant. The genotoxic and mutagenic effects in tobacco farmers were investigated. In order to verify the relationship between genetic susceptibility and biomarkers GSTT1, GSTM1, GSTP1, CYP2A6, PON, OGG1, RAD51, XRCC1, and XRCC4 genes polymorphism were evaluated. Oxidative stress markers and trace elements content were determined. Peripheral blood cells samples were collected from 111 agricultural workers during pesticides application and leaf harvest, and 56 non-exposed subjects. Results show that farmers are exposed to mixture of substances with genotoxic and cytotoxic potential. Only GSTM1 null and CYP2A6*9 showed significant associations with cytokinesis-blocked micronuclei assay results. In pesticide application an increase in trace elements content was observed. The results indicated that exposure to pesticides and nicotine can influence antioxidant enzymes activity. Our study drives the attention once more to the need for occupational training on safe work environment for farm workers. PMID:22614024

  20. Indian spice curcumin may be an effective strategy to combat the genotoxicity of arsenic in Swiss albino mice.

    PubMed

    Biswas, Jaydip; Roy, Soumi; Mukherjee, Sutapa; Sinha, Dona; Roy, Madhumita

    2010-01-01

    Inorganic arsenic (As) is considered as a human carcinogen because it is associated with cancers of skin, lung, liver and bladder in exposed population. Consumption of As contaminated ground water for long term causes oxidative stress. Generation of reactive oxygen species (ROS), beyond the body's endogenous antioxidant balance results severe imbalance of the cellular antioxidant defense mechanism. The present study was conducted to investigate the antioxidative effect of curcumin against sodium arsenite (As III) induced oxidative damage in Swiss albino mice. Bio-monitoring with comet assay and micronucleus assay revealed that the increase in genotoxicity caused by As III was counteracted when mice were orally administered with 5, 10 and 15 mg curcumin kg-1 bw (body weight) daily. ROS generation, lipid peroxidation and protein carbonyl content, which were elevated by As III, were reduced when treated with curcumin. Curcumin also exhibited protective action against the As III induced depletion of antioxidants like catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST) and glutathione (GSH) in mice liver tissue. Thus the present work provides a direct evidence for the involvement of curcumin in reducing As III induced oxidative stress in Swiss albino mice by virtue of its antioxidant potential and trapping of free radicals. PMID:20593964

  1. Indian spice curcumin may be an effective strategy to combat the genotoxicity of arsenic in Swiss albino mice.

    PubMed

    Biswas, Jaydip; Roy, Soumi; Mukherjee, Sutapa; Sinha, Dona; Roy, Madhumita

    2010-01-01

    Inorganic arsenic (As) is considered as a human carcinogen because it is associated with cancers of skin, lung, liver and bladder in exposed population. Consumption of As contaminated ground water for long term causes oxidative stress. Generation of reactive oxygen species (ROS), beyond the body's endogenous antioxidant balance results severe imbalance of the cellular antioxidant defense mechanism. The present study was conducted to investigate the antioxidative effect of curcumin against sodium arsenite (As III) induced oxidative damage in Swiss albino mice. Bio-monitoring with comet assay and micronucleus assay revealed that the increase in genotoxicity caused by As III was counteracted when mice were orally administered with 5, 10 and 15 mg curcumin kg-1 bw (body weight) daily. ROS generation, lipid peroxidation and protein carbonyl content, which were elevated by As III, were reduced when treated with curcumin. Curcumin also exhibited protective action against the As III induced depletion of antioxidants like catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST) and glutathione (GSH) in mice liver tissue. Thus the present work provides a direct evidence for the involvement of curcumin in reducing As III induced oxidative stress in Swiss albino mice by virtue of its antioxidant potential and trapping of free radicals.

  2. Pyruvate remediation of cell stress and genotoxicity induced by haloacetic acid drinking water disinfection by-products.

    PubMed

    Dad, Azra; Jeong, Clara H; Pals, Justin A; Wagner, Elizabeth D; Plewa, Michael J

    2013-10-01

    Monohaloacetic acids (monoHAAs) are a major class of drinking water disinfection by-products (DBPs) and are cytotoxic, genotoxic, mutagenic, and teratogenic. We propose a model of toxic action based on monoHAA-mediated inhibition of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as a target cytosolic enzyme. This model predicts that GAPDH inhibition by the monoHAAs will lead to a severe reduction of cellular ATP levels and repress the generation of pyruvate. A loss of pyruvate will lead to mitochondrial stress and genomic DNA damage. We found a concentration-dependent reduction of ATP in Chinese hamster ovary cells after monoHAA treatment. ATP reduction per pmol monoHAA followed the pattern of iodoacetic acid (IAA) > bromoacetic acid (BAA) > chloroacetic acid (CAA), which is the pattern of potency observed with many toxicological endpoints. Exogenous supplementation with pyruvate enhanced ATP levels and attenuated monoHAA-induced genomic DNA damage as measured with single cell gel electrophoresis. These data were highly correlated with the SN 2 alkylating potentials of the monoHAAs and with the induction of toxicity. The results from this study strongly support the hypothesis that GAPDH inhibition and the possible subsequent generation of reactive oxygen species is linked with the cytotoxicity, genotoxicity, teratogenicity, and neurotoxicity of these DBPs.

  3. Pyruvate Remediation of Cell Stress and Genotoxicity Induced by Haloacetic Acid Drinking Water Disinfection By-Products

    PubMed Central

    Dad, Azra; Jeong, Clara H.; Pals, Justin A.; Wagner, Elizabeth D.; Plewa, Michael J.

    2014-01-01

    Monohaloacetic acids (monoHAAs) are a major class of drinking water disinfection by-products (DBPs) and are cytotoxic, genotoxic, mutagenic, and teratogenic. We propose a model of toxic action based on monoHAA-mediated inhibition of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as a target cytosolic enzyme. This model predicts that GAPDH inhibition by the monoHAAs will lead to a severe reduction of cellular ATP levels and repress the generation of pyruvate. A loss of pyruvate will lead to mitochondrial stress and genomic DNA damage. We found a concentration-dependent reduction of ATP in Chinese hamster ovary cells after monoHAA treatment. ATP reduction per pmol monoHAA followed the pattern of iodoacetic acid (IAA) > bromoacetic acid (BAA) >> chloroacetic acid (CAA), which is the pattern of potency observed with many toxicological endpoints. Exogenous supplementation with pyruvate enhanced ATP levels and attenuated monoHAA-induced genomic DNA damage as measured with single cell gel electrophoresis. These data were highly correlated with the SN2 alkylating potentials of the monoHAAs and with the induction of toxicity. The results from this study strongly support the hypothesis that GAPDH inhibition and the possible subsequent generation of reactive oxygen species is linked with the cytotoxicity, genotoxicity, teratogenicity, and neurotoxicity of these DBPs. PMID:23893730

  4. Effect of afobazole on genotoxic effects of tobacco smoke in the placenta and embryonic tissues of rats.

    PubMed

    Durnev, A D; Solomina, A S; Zhanataev, A K; Zhukov, V N; Seredenin, S B

    2010-09-01

    The DNA comet assay was used to evaluate the severity of genotoxic changes in embryonic tissues and placenta of rats daily exposed to tobacco smoke per se or in combination with an anxiolytic agent afobazole. The exposure to tobacco smoke (4 cigarettes containing 13 mg tar and 1 mg nicotine per 72 dm(3)) for 20 min on days 1-13 of pregnancy increased the degree of DNA damage and elevation of apoptotic DNA comets in cells of the placenta and embryo from pregnant rats. Afobazole (1 and 10 mg/kg orally) reduced the genotoxic effect of tobacco smoke and decreased the amount of apoptotic DNA comets in placental tissue and embryonic tissue from rats. PMID:21246089

  5. Differential effects of Glycyrrhiza species on genotoxic estrogen metabolism: licochalcone A downregulates P450 1B1 whereas isoliquiritigenin stimulates

    PubMed Central

    Dunlap, Tareisha L.; Wang, Shuai; Simmler, Charlotte; Chen, Shao-Nong; Pauli, Guido F.; Dietz, Birgit M.; Bolton, Judy L.

    2015-01-01

    Estrogen chemical carcinogenesis involves 4-hydroxylation of estrone/estradiol (E1/E2) by P450 1B1, generating catechol and quinone genotoxic metabolites that cause DNA mutations and initiate/promote breast cancer. Inflammation enhances this effect by up-regulating P450 1B1. The present study tested the three authenticated medicinal species of licorice, [Glycyrrhiza glabra (GG), G. uralensis (GU), and G. inflata (GI)], used by women as dietary supplements, for their anti-inflammatory activities and their ability to modulate estrogen metabolism. The pure compounds, liquiritigenin (LigF), its chalcone isomer isoliquiritigenin (LigC), and the GI specific licochalcone A (LicA) were also tested. The licorice extracts and compounds were evaluated for anti-inflammatory activity by measuring inhibition of iNOS activity in macrophage cells: GI > GG > GU and LigC ≅ LicA > LigF. The Michael acceptor chalcone LicA, is likely responsible for the anti-inflammatory activity of GI. A sensitive LC-MS/MS assay was employed to quantify estrogen metabolism by measuring 2-MeOE1 as non-toxic and 4-MeOE1 as genotoxic biomarkers in the non-tumorigenic human mammary epithelial cell line, MCF-10A. GG, GU, and LigC increased 4-MeOE1, whereas GI and LicA inhibited 2- and 4-MeOE1 levels. GG, GU (5 μg/mL), and LigC (1 μM) also enhanced P450 1B1 expression and activities, which was further increased by inflammatory cytokines (TNF-α and IFN-γ). LicA (1 μM, 10 μM) decreased cytokine- and TCDD-induced, P450 1B1 gene expression and TCDD-induced xenobiotic response element luciferase reporter (IC50=12.3 μM), suggesting an antagonistic effect on the aryl hydrocarbon receptor, which regulates P450 1B1. Similarly, GI (5 μg/mL) reduced cytokine- and TCDD-induced P450 1B1 gene expression. Collectively, these data suggest that of the three licorice species that are used in botanical supplements, GI represents the most promising chemopreventive licorice extract for women’s health. Additionally

  6. Toxic and genotoxic effects of the 2,4-dichlorophenoxyacetic acid (2,4-D)-based herbicide on the Neotropical fish Cnesterodon decemmaculatus.

    PubMed

    Ruiz de Arcaute, C; Soloneski, S; Larramendy, M L

    2016-06-01

    Acute toxicity and genotoxicity of the 54.8% 2,4-D-based commercial herbicide DMA® were assayed on Cnesterodon decemmaculatus (Pisces, Poeciliidae). Whereas lethal effect was used as the end point for mortality, frequency of micronuclei (MNs), other nuclear abnormalities and primary DNA damage evaluated by the single cell gel electrophoresis (SCGE) assay were employed as end points for genotoxicity. Mortality studies demonstrated an LC50 96 h value of 1008 mg/L (range, 929-1070) of 2,4-D. Behavioral changes, e.g., gathering at the bottom of the aquarium, slowness in motion, slow reaction and abnormal swimming were observed. Exposure to 2,4-D within the 252-756 mg/L range increased the frequency of MNs in fish exposed for both 48 and 96 h. Whereas blebbed nuclei were induced in treatments lasting for 48 and 96 h, notched nuclei were only induced in fish exposed for 96 h. Regardless of both concentration and exposure time, 2,4-D did not induce lobed nuclei and binucleated erythrocytes. In addition, we found that exposure to 2,4-D within the 252-756 mg/L range increased the genetic damage index in treatments lasting for either 48 and 96 h. The results represent the first experimental evidence of the lethal and several sublethal effects, including behavioral alterations and two genotoxic properties namely the induction of MNs and primary DNA strand breaks, exerted by 2,4-D on an endemic organism as C. decemmaculatus.

  7. In Vivo Effects of Vanadium Pentoxide and Antioxidants (Ascorbic Acid and Alpha-Tocopherol) on Apoptotic, Cytotoxic, and Genotoxic Damage in Peripheral Blood of Mice.

    PubMed

    García-Rodríguez, María Del Carmen; Hernández-Cortés, Lourdes Montserrat; Altamirano-Lozano, Mario Agustín

    2016-01-01

    This study was conducted to investigate the effects of vanadium pentoxide (V2O5), ascorbic acid (AA), and alpha-tocopherol (α-TOH) on apoptotic, cytotoxic, and genotoxic activity. Groups of five Hsd:ICR mice were treated with the following: (a) vehicle, distilled water; (b) vehicle, corn oil; (c) AA, 100 mg/kg intraperitoneally (ip); (d) α-TOH, 20 mg/kg by gavage; (e) V2O5, 40 mg/kg by ip injection; (f) AA + V2O5; and (g) α-TOH + V2O5. Genotoxic damage was evaluated by examining micronucleated polychromatic erythrocytes (MN-PCE) obtained from the caudal vein at 0, 24, 48, and 72 h after treatments. Induction of apoptosis and cell viability were assessed at 48 h after treatment in nucleated cells of peripheral blood. Treatment with AA alone reduced basal MN-PCE, while V2O5 treatment marginally increased MN-PCE at all times after injection. Antioxidants treatments prior to V2O5 administration decreased MN-PCE compared to the V2O5 group, with the most significant effect in the AA + V2O5 group. The apoptotic cells increased with all treatments, suggesting that this process may contribute to the elimination of the cells with V2O5-induced DNA damage (MN-PCE). The necrotic cells only increased in the V2O5 group. Therefore, antioxidants such as AA and α-TOH can be used effectively to protect or reduce the genotoxic effects induced by vanadium compounds like V2O5. PMID:27413422

  8. In Vivo Effects of Vanadium Pentoxide and Antioxidants (Ascorbic Acid and Alpha-Tocopherol) on Apoptotic, Cytotoxic, and Genotoxic Damage in Peripheral Blood of Mice

    PubMed Central

    García-Rodríguez, María del Carmen; Hernández-Cortés, Lourdes Montserrat; Altamirano-Lozano, Mario Agustín

    2016-01-01

    This study was conducted to investigate the effects of vanadium pentoxide (V2O5), ascorbic acid (AA), and alpha-tocopherol (α-TOH) on apoptotic, cytotoxic, and genotoxic activity. Groups of five Hsd:ICR mice were treated with the following: (a) vehicle, distilled water; (b) vehicle, corn oil; (c) AA, 100 mg/kg intraperitoneally (ip); (d) α-TOH, 20 mg/kg by gavage; (e) V2O5, 40 mg/kg by ip injection; (f) AA + V2O5; and (g) α-TOH + V2O5. Genotoxic damage was evaluated by examining micronucleated polychromatic erythrocytes (MN-PCE) obtained from the caudal vein at 0, 24, 48, and 72 h after treatments. Induction of apoptosis and cell viability were assessed at 48 h after treatment in nucleated cells of peripheral blood. Treatment with AA alone reduced basal MN-PCE, while V2O5 treatment marginally increased MN-PCE at all times after injection. Antioxidants treatments prior to V2O5 administration decreased MN-PCE compared to the V2O5 group, with the most significant effect in the AA + V2O5 group. The apoptotic cells increased with all treatments, suggesting that this process may contribute to the elimination of the cells with V2O5-induced DNA damage (MN-PCE). The necrotic cells only increased in the V2O5 group. Therefore, antioxidants such as AA and α-TOH can be used effectively to protect or reduce the genotoxic effects induced by vanadium compounds like V2O5. PMID:27413422

  9. Evaluation of genotoxic effects of surface waters using a battery of bioassays indicating different mode of action.

    PubMed

    Han, Yingnan; Li, Na; Oda, Yoshimitsu; Ma, Mei; Rao, Kaifeng; Wang, Zijian; Jin, Wei; Hong, Gang; Li, Zhiguo; Luo, Yi

    2016-11-01

    With the burgeoning contamination of surface waters threatening human health, the genotoxic effects of surface waters have received much attention. Because mutagenic and carcinogenic compounds in water cause tumors by different mechanisms, a battery of bioassays that each indicate a different mode of action (MOA) is required to evaluate the genotoxic effects of contaminants in water samples. In this study, 15 water samples from two source water reservoirs and surrounding rivers in Shijiazhuang city of China were evaluated for genotoxic effects. Target chemical analyses of 14 genotoxic pollutants were performed according to the Environmental quality standards for surface water of China. Then, the in vitro cytokinesis-block micronucleus (CBMN) assay, based on a high-content screening technique, was used to detect the effect of chromosome damage. The SOS/umu test using strain TA1535/pSK1002 was used to detect effects on SOS repair of gene expression. Additionally, two other strains, NM2009 and NM3009, which are highly sensitive to aromatic amines and nitroarenes, respectively, were used in the SOS/umu test to avoid false negative results. In the water samples, only two of the genotoxic chemicals listed in the water standards were detected in a few samples, with concentrations that were below water quality standards. However, positive results for the CBMN assay were observed in two river samples, and positive results for the induction of umuC gene expression in TA1535/pSK1002 were observed in seven river samples. Moreover, positive results were observed for NM2009 with S9 and NM3009 without S9 in some samples that had negative results using the strain TA1535/pSK1002. Based on the results with NM2009 and NM3009, some unknown or undetected aromatic amines and nitroarenes were likely in the source water reservoirs and the surrounding rivers. Furthermore, these compounds were most likely the causative pollutants for the genotoxic effect of these water samples. Therefore

  10. Cell-Based Genotoxicity Testing

    NASA Astrophysics Data System (ADS)

    Reifferscheid, Georg; Buchinger, Sebastian

    Genotoxicity test systems that are based on bacteria display an important role in the detection and assessment of DNA damaging chemicals. They belong to the basic line of test systems due to their easy realization, rapidness, broad applicability, high sensitivity and good reproducibility. Since the development of the Salmonella microsomal mutagenicity assay by Ames and coworkers in the early 1970s, significant development in bacterial genotoxicity assays was achieved and is still a subject matter of research. The basic principle of the mutagenicity assay is a reversion of a growth inhibited bacterial strain, e.g., due to auxotrophy, back to a fast growing phenotype (regain of prototrophy). Deeper knowledge of the ­mutation events allows a mechanistic understanding of the induced DNA-damage by the utilization of base specific tester strains. Collections of such specific tester strains were extended by genetic engineering. Beside the reversion assays, test systems utilizing the bacterial SOS-response were invented. These methods are based on the fusion of various SOS-responsive promoters with a broad variety of reporter genes facilitating numerous methods of signal detection. A very important aspect of genotoxicity testing is the bioactivation of ­xenobiotics to DNA-damaging compounds. Most widely used is the extracellular metabolic activation by making use of rodent liver homogenates. Again, genetic engineering allows the construction of highly sophisticated bacterial tester strains with significantly enhanced sensitivity due to overexpression of enzymes that are involved in the metabolism of xenobiotics. This provides mechanistic insights into the toxification and detoxification pathways of xenobiotics and helps explaining the chemical nature of hazardous substances in unknown mixtures. In summary, beginning with "natural" tester strains the rational design of bacteria led to highly specific and sensitive tools for a rapid, reliable and cost effective ­genotoxicity

  11. ASSESSING HUMAN EXPOSURE AND GENOTOXIC EFFECTS IN HUMAN EXFOLIATED EPITHELIA FROM INDIVDUALS IVING IN AN ENDEMIC REGION IN INNER MONGOLAI

    EPA Science Inventory

    A pilot study was conducted to characterize arsenic exposure and genotoxic effects in Ba Men located in West Central Inner Mongolia in an attempt to identify biomarkers useful for assessing health risk resulting from chronic arsenic exposure. The study subjects included 19 high ...

  12. Analysis of the Genotoxic Effects of Mobile Phone Radiation using Buccal Micronucleus Assay: A Comparative Evaluation

    PubMed Central

    Singh, Narendra Nath; Sreedhar, Gadiputi; Mukherjee, Saikat

    2016-01-01

    Introduction Micronucleus (MN) is considered to be a reliable marker for genotoxic damage and it determines the presence and the extent of the chromosomal damage. The MN is formed due to DNA damage or chromosomal disarrangements. The MN has a close association with cancer incidences. In the new era, mobile phones are constantly gaining popularity specifically in the young generation, but this device uses radiofrequency radiation that may have a possible carcinogenic effect. The available reports related to the carcinogenic effect of mobile radiation on oral mucosa are contradictory. Aim To explore the effects of mobile phone radiation on the MN frequency in oral mucosal cells. Materials and Methods The subjects were divided into two major groups: low mobile phone users and high mobile phone users. Subjects who used their mobile phone since less than five years and less than three hours a week comprised of the first group and those who used their mobile since more than five years and more than 10 hours a week comprised of the second group. Net surfing and text messaging was not considered in this study. Exfoliated buccal mucosal cells were collected from both the groups and the cells were stained with DNA-specific stain acridine orange. Thousand exfoliated buccal mucosal cells were screened and the cells which were positive for micronuclei were counted. The micronucleus frequency was represented as mean±SD, and unpaired Student t-test was used for intergroup comparisons. Results The number of micronucleated cells/ 1000 exfoliated buccal mucosal cells was found to be significantly increased in high mobile phone users group than the low mobile phone users group. The use of mobile phone with the associated complaint of warmth around the ear showed a maximum increase in the number of micronucleated cells /1000 exfoliated buccal mucosal cells. Conclusion Mobile phone radiation even in the permissible range when used for longer duration causes significant genotoxicity

  13. Human mesenchymal stem cells are resistant to cytotoxic and genotoxic effects of cisplatin in vitro

    PubMed Central

    Bellagamba, Bruno Corrêa; de Abreu, Bianca Regina Ribas; Grivicich, Ivana; Markarian, Carolina Franke; Chem, Eduardo; Camassola, Melissa; Nardi, Nance Beyer; Dihl, Rafael Rodrigues

    2016-01-01

    Abstract Mesenchymal stem cells (MSCs) are known for their important properties involving multilineage differentiation potential., trophic factor secretion and localization along various organs and tissues. On the dark side, MSCs play a distinguished role in tumor microenvironments by differentiating into tumor-associated fibroblasts or supporting tumor growth via distinct mechanisms. Cisplatin (CIS) is a drug widely applied in the treatment of a large number of cancers and is known for its cytotoxic and genotoxic effects, both in vitro and in vivo. Here we assessed the effects of CIS on MSCs and the ovarian cancer cell line OVCAR-3, by MTT and comet assays. Our results demonstrated the resistance of MSCs to cell death and DNA damage induction by CIS, which was not observed when OVCAR-3 cells were exposed to this drug. PMID:27007906

  14. Studies on the genotoxic effect of beryllium chloride and the possible protective role of selenium/vitamins A, C and E.

    PubMed

    Fahmy, Maha A; Hassan, Nagwa H A; Farghaly, Ayman A; Hassan, Entesar E S

    2008-04-30

    The genotoxic potential of beryllium chloride (BeCl2) was evaluated in vivo in mice using different endpoints. Chromosomal aberrations in bone marrow cells and in spermatocytes as well as sperm abnormalities were determined in the tested mice. The protective role of an orally administered drug consisting of selenium and vitamins A, C and E (selenium-ACE) was also studied. For analysis of chromosomal aberrations, both single and repeated oral treatments for a period of 3 weeks were performed. The doses used were 93.75, 187.50, 375, and 750 mg BeCl2/kg bw, which corresponds to 1/16, 1/8, 1/4, and 1/2 of the experimental LD50. BeCl2 induced a statistically significant increase in the percentage of chromosomal aberrations in both somatic and germ cells, with a dose- and time-response. The percentage of induced chromosomal aberrations was significantly reduced in all BeCl2-treated groups after oral administration of selenium-ACE. Beryllium chloride also induced a significant increase in the percentage of abnormal sperm. This percentage reached values of 9.62 +/- 0.32 and 5.56 +/- 0.31 in mice treated with the highest test dose of BeCl2 and with BeCl2+selenium-ACE, respectively, compared with 1.96 +/- 0.14 for the control. In conclusion, the results demonstrate the genotoxic effect of beryllium chloride and confirm the protective role of selenium-ACE against the genotoxicity of beryllium chloride.

  15. Determination of chemical composition and genotoxic effects of essential oil obtained from Nepeta nuda on Zea mays seedlings.

    PubMed

    Bozari, Sedat; Agar, Guleray; Aksakal, Ozkan; Erturk, Filiz A; Yanmis, Derya

    2013-05-01

    We aimed to determine the genotoxic potential of essential oil (EO) obtained from Nepeta nuda. The chemical content of EO was measured via gas chromatography/mass spectrometry. The most abundant contents were 4aα,7β,7aα-nepetalactone (18.10%), germacrene (15.68%) and elemol (14.38%). For genotoxic effects of EO, Zea mays' seeds were exposed to four different concentrations of this oil. Inhibition of root and stem growth were observed with an increase in EO concentrations. Randomly amplified polymorphic DNA (RAPD) method was used to determine the genotoxic effects of EO. Some changes occurred in RAPD profiles of germinated EO-treated seeds. Even though total soluble protein quantity vary, the data observed from the protein profiles of sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) showed that there was a little differentiation between band profiles of treated samples and control group. We concluded that the basis of interactions between plants, like allelopathy, may be related with genotoxic effects of EO.

  16. Determination of chemical composition and genotoxic effects of essential oil obtained from Nepeta nuda on Zea mays seedlings.

    PubMed

    Bozari, Sedat; Agar, Guleray; Aksakal, Ozkan; Erturk, Filiz A; Yanmis, Derya

    2013-05-01

    We aimed to determine the genotoxic potential of essential oil (EO) obtained from Nepeta nuda. The chemical content of EO was measured via gas chromatography/mass spectrometry. The most abundant contents were 4aα,7β,7aα-nepetalactone (18.10%), germacrene (15.68%) and elemol (14.38%). For genotoxic effects of EO, Zea mays' seeds were exposed to four different concentrations of this oil. Inhibition of root and stem growth were observed with an increase in EO concentrations. Randomly amplified polymorphic DNA (RAPD) method was used to determine the genotoxic effects of EO. Some changes occurred in RAPD profiles of germinated EO-treated seeds. Even though total soluble protein quantity vary, the data observed from the protein profiles of sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) showed that there was a little differentiation between band profiles of treated samples and control group. We concluded that the basis of interactions between plants, like allelopathy, may be related with genotoxic effects of EO. PMID:22312034

  17. Cytotoxic and genotoxic effects of tambjamine D, an alkaloid isolated from the nudibranch Tambja eliora, on Chinese hamster lung fibroblasts.

    PubMed

    Cavalcanti, Bruno C; Júnior, Hélio V N; Seleghim, Mirna H R; Berlinck, Roberto G S; Cunha, Geanne M A; Moraes, Manoel O; Pessoa, Claudia

    2008-08-11

    Marine organisms have been shown to be potential sources of bioactive compounds with pharmaceutical applications. Previous chemical investigation of the nudibranch Tambja eliora led to the isolation of the alkaloid tambjamine D. Tambjamines have been isolated from marine sources and belong to the family of 4-methoxypyrrolic-derived natural products, which display promising immunosuppressive and cytotoxic properties. Their ability to intercalate DNA and their pro-oxidant activity may be related to some of the biological effects of the 4-methoxypyrrolic alkaloids. The aim of the present investigation was to determine the cytotoxic, pro-oxidant and genotoxic properties of tambjamine D in V79 Chinese hamster lung fibroblast cells. Tambjamine D displayed a potent cytotoxic effect in V79 cells (IC50 1.2 microg/mL) evaluated by the MTT assay. Based on the MTT result, V79 cells were treated with different concentrations of tambjamine D (0.6, 1.2, 2.4 and 4.8 microg/mL). After 24h, tambjamine D reduced the number of viable cells in a concentration-dependent way at all concentrations tested, assessed by the trypan blue dye exclusion test. The hemolytic assay showed that the cytotoxic activity of tambjamine D was not related to membrane disruption (EC50>100 microg/mL). Tambjamine D increased the number of apoptotic cells in a concentration-dependent manner at all concentrations tested according to acridine orange/ethidium bromide staining, showing that the alkaloid cytotoxic effect was related to the induction of apoptosis. MTT reduction was stimulated by tambjamine D, which may indicate the generation of reactive oxygen species. Accordingly, treatment of cells with tambjamine D increased nitrite/nitrate at all concentrations and TBARS production starting at the concentration corresponding to the IC50. Tambjamine D, also, induced DNA strand breaks and increased the micronucleus cell frequency as evaluated by comet and micronucleus tests, respectively, at all concentrations

  18. Cobalt and antimony: genotoxicity and carcinogenicity.

    PubMed

    De Boeck, Marlies; Kirsch-Volders, Micheline; Lison, Dominique

    2003-12-10

    The purpose of this review is to summarise the data concerning genotoxicity and carcinogenicity of Co and Sb. Both metals have multiple industrial and/or therapeutical applications, depending on the considered species. Cobalt is used for the production of alloys and hard metal (cemented carbide), diamond polishing, drying agents, pigments and catalysts. Occupational exposure to cobalt may result in adverse health effects in different organs or tissues. Antimony trioxide is primarily used as a flame retardant in rubber, plastics, pigments, adhesives, textiles, and paper. Antimony potassium tartrate has been used worldwide as an anti-shistosomal drug. Pentavalent antimony compounds have been used for the treatment of leishmaniasis. Co(II) ions are genotoxic in vitro and in vivo, and carcinogenic in rodents. Co metal is genotoxic in vitro. Hard metal dust, of which occupational exposure is linked to an increased lung cancer risk, is proven to be genotoxic in vitro and in vivo. Possibly, production of active oxygen species and/or DNA repair inhibition are mechanisms involved. Given the recently provided proof for in vitro and in vivo genotoxic potential of hard metal dust, the mechanistic evidence of elevated production of active oxygen species and the epidemiological data on increased cancer risk, it may be advisable to consider the possibility of a new evaluation by IARC. Both trivalent and pentavalent antimony compounds are generally negative in non-mammalian genotoxicity tests, while mammalian test systems usually give positive results for Sb(III) and negative results for Sb(V) compounds. Assessment of the in vivo potential of Sb2O3 to induce chromosome aberrations (CA) gave conflicting results. Animal carcinogenicity data were concluded sufficient for Sb2O3 by IARC. Human carcinogenicity data is difficult to evaluate given the frequent co-exposure to arsenic. Possible mechanisms of action, including potential to produce active oxygen species and to interfere with

  19. In Vivo and In Vitro Genotoxic and Epigenetic Effects of Two Types of Cola Beverages and Caffeine: A Multiassay Approach.

    PubMed

    Mateo-Fernández, Marcos; Merinas-Amo, Tania; Moreno-Millán, Miguel; Alonso-Moraga, Ángeles; Demyda-Peyrás, Sebastián

    2016-01-01

    The aim of this work was to assess the biological and food safety of two different beverages: Classic Coca Cola™ (CCC) and Caffeine-Free Coca Cola (CFCC). To this end, we determined the genotoxicological and biological effects of different doses of lyophilised CCC and CFCC and Caffeine (CAF), the main distinctive constituent. Their toxic/antitoxic, genotoxic/antigenotoxic, and chronic toxicity (lifespan assay) effects were determined in vivo using the Drosophila model. Their cytotoxic activities were determined using the HL-60 in vitro cancer model. In addition, clastogenic DNA toxicity was measured using internucleosomal fragmentation and SCGE assays. Their epigenetic effects were assessed on the HL-60 methylation status using some repetitive elements. The experimental results showed a slight chemopreventive effect of the two cola beverages against HL-60 leukaemia cells, probably mediated by nonapoptotic mechanisms. Finally, CCC and CAF induced a global genome hypomethylation evaluated in LINE-1 and Alu M1 repetitive elements. Overall, we demonstrated for the first time the safety of this famous beverage in in vivo and in vitro models.

  20. In Vivo and In Vitro Genotoxic and Epigenetic Effects of Two Types of Cola Beverages and Caffeine: A Multiassay Approach

    PubMed Central

    Merinas-Amo, Tania; Moreno-Millán, Miguel; Alonso-Moraga, Ángeles; Demyda-Peyrás, Sebastián

    2016-01-01

    The aim of this work was to assess the biological and food safety of two different beverages: Classic Coca Cola™ (CCC) and Caffeine-Free Coca Cola (CFCC). To this end, we determined the genotoxicological and biological effects of different doses of lyophilised CCC and CFCC and Caffeine (CAF), the main distinctive constituent. Their toxic/antitoxic, genotoxic/antigenotoxic, and chronic toxicity (lifespan assay) effects were determined in vivo using the Drosophila model. Their cytotoxic activities were determined using the HL-60 in vitro cancer model. In addition, clastogenic DNA toxicity was measured using internucleosomal fragmentation and SCGE assays. Their epigenetic effects were assessed on the HL-60 methylation status using some repetitive elements. The experimental results showed a slight chemopreventive effect of the two cola beverages against HL-60 leukaemia cells, probably mediated by nonapoptotic mechanisms. Finally, CCC and CAF induced a global genome hypomethylation evaluated in LINE-1 and Alu M1 repetitive elements. Overall, we demonstrated for the first time the safety of this famous beverage in in vivo and in vitro models. PMID:27471731

  1. In Vivo and In Vitro Genotoxic and Epigenetic Effects of Two Types of Cola Beverages and Caffeine: A Multiassay Approach.

    PubMed

    Mateo-Fernández, Marcos; Merinas-Amo, Tania; Moreno-Millán, Miguel; Alonso-Moraga, Ángeles; Demyda-Peyrás, Sebastián

    2016-01-01

    The aim of this work was to assess the biological and food safety of two different beverages: Classic Coca Cola™ (CCC) and Caffeine-Free Coca Cola (CFCC). To this end, we determined the genotoxicological and biological effects of different doses of lyophilised CCC and CFCC and Caffeine (CAF), the main distinctive constituent. Their toxic/antitoxic, genotoxic/antigenotoxic, and chronic toxicity (lifespan assay) effects were determined in vivo using the Drosophila model. Their cytotoxic activities were determined using the HL-60 in vitro cancer model. In addition, clastogenic DNA toxicity was measured using internucleosomal fragmentation and SCGE assays. Their epigenetic effects were assessed on the HL-60 methylation status using some repetitive elements. The experimental results showed a slight chemopreventive effect of the two cola beverages against HL-60 leukaemia cells, probably mediated by nonapoptotic mechanisms. Finally, CCC and CAF induced a global genome hypomethylation evaluated in LINE-1 and Alu M1 repetitive elements. Overall, we demonstrated for the first time the safety of this famous beverage in in vivo and in vitro models. PMID:27471731

  2. Studies on genotoxicity of orally administered crocidolite asbestos in rats: implications for ingested asbestos induced carcinogenesis.

    PubMed

    Varga, C; Pocsai, Z; Horváth, G; Timbrell, V

    1996-01-01

    The early genotoxic action of oral exposure to UICC crocidolite asbestos fibres was studied in different short-term tests. Fischer-344 rats were gavaged with 50 mg/b.w.kg untreated asbestos fibres and fibres which had been allowed to adsorb benzo(a)pyrene molecules from extremely low concentration (0.25-2.5 microg/ml) aqueous solutions. This system can be considered a model for the drinking of potable water contaminated by asbestos fibres together with biologically active organic micro-pollutants. The Ames Salmonella mutagenicity assay was performed on concentrated urine and serum samples of treated animals. The formation of micronuclei and sister chromatid exchanges was also studied in the bone marrow of the exposed rats. The micronucleus analysis indicated marginal genotoxic activity only upon treatment with crocidolite prepared from the solution of 1 microg/ml. A dose-dependent increase was, however, demonstrated in the sister chromatid exchange frequency upon treatment with benzo(a)pyrene coated fibres. These experiments suggest the acute cogenotoxic activity of such fibres in orally exposed animals. PMID:8687133

  3. Inhibition of sulfotransferase affecting in vivo genotoxicity and DNA adducts induced by safrole in rat liver.

    PubMed

    Daimon, H; Sawada, S; Asakura, S; Sagami, F

    The effect of pretreatment with pentachlorophenol (PCP), a known inhibitor of sulfotransferases, on the induction of chromosomal aberrations, sister chromatid exchanges (SCEs), replicative DNA synthesis (RDS), and the formation of DNA adducts was studied in the liver of rats treated with safrole (1-allyl-3,4-methylenedioxy-benzene). Rats were given a single oral dose (1,000 mg/kg body weight) or 5 repeated doses (500 mg/kg body weight) of safrole, with or without intraperitoneal pretreatment with PCP (10 mg/kg body weight). Hepatocytes were isolated 24 hr after administration of safrole and allowed to proliferate in Williams' medium E supplemented with epidermal growth factor to test for chromosomal aberrations and SCEs. For examination of RDS, hepatocytes were incubated in Williams' medium E containing 5-bromo-2'-deoxyuridine. Safrole-DNA adducts were detected by a nuclease P1-enhanced 32P-postlabeling assay. A single dose of safrole induced significant SCEs and RDS, while chromosomal aberrations were induced by 5 repeated doses. Two major and 2 minor DNA adducts were detected by both a single dose and 5 repeated doses. PCP significantly decreased safrole-induced cytogenetic effects and RDS, and caused a decrease in DNA adducts formed by safrole. These results suggest that safrole is capable of inducing SCEs, chromosomal aberrations, and RDS in the rat liver in vivo and that these effects may be induced by the sulfuric acid ester metabolite that can bind DNA.

  4. Biomonitoring of genotoxic effects for human exposure to nanomaterials: The challenge ahead.

    PubMed

    Gonzalez, Laetitia; Kirsch-Volders, Micheline

    2016-01-01

    Exposures to nanomaterials (NMs), with their specific physico-chemical characteristics, are likely to increase over the next years, as their production for industrial, consumer and medical applications is steadily rising. Therefore, there is an urgent need for the implementation of human biomonitoring studies of genotoxic effects after NM exposures in order to monitor and assure safety for workers and the general population. In this review, most commonly used biomarkers of early genetic effects were analyzed for their adequacy after NM exposures. A more in depth analysis of the ex vivo/in vitro lymphocyte MN assay was performed, although, in literature no studies are available using this assay for NM exposures. Therefore, the known factors determining the NMs tissue/cellular targets and the multiplicity of modes of action of NMs were summarized. The main pending questions are whether (1) lymphocytes are a NM target or an adequate surrogate tissue, (2) whether the buccal MN assay might be more suitable for NM exposures via inhalation or ingestion, as buccal cells might be exposed more directly. While the current state-of-the-art does not allow for drawing firm conclusions, major research gaps are identified and some cautious recommendations can be formulated. Therefore in vitro and in vivo studies should be conducted comparing methodologies side-by-side in the same subjects and for different types of NMs. The ex vivo/in vitro MN assay in its automated version, allowing objective analysis of large cohorts and detection of direct and indirect genotoxic effects, remains a valuable candidate for human biomonitoring to NM exposure. Considering the potential cancer risk from exposure to NMs and previous dramatic experiences with too late surveillance of occupational exposures to similar substances (e.g. to asbestos), there is an urgent need to define and implement adequate scientifically sound biomonitoring methods and programme for exposure to NMs. PMID:27234560

  5. Toxic and genotoxic effects of Roundup on tadpoles of the Indian skittering frog (Euflictis cyanophlyctis) in the presence and absence of predator stress.

    PubMed

    Yadav, Sushama Singh; Giri, Sarbani; Singha, Utsab; Boro, Freeman; Giri, Anirudha

    2013-05-15

    Glyphosate, a post emergent herbicide, has become the backbone of no-till agriculture and is considered safe for animals. However, the impact of glyphosate on non-target organisms, especially on amphibians, is the subject of major concern and debate in recent times. We examined the toxic and genotoxic effects of Roundup, a commercial formulation of glyphosate, in the tadpoles of the Indian skittering frog (Euflictis cyanophlyctis). Roundup at different concentrations (0, 1, 2, 3, 4 and 8mg acid equivalent (ae)/L), tested in a 2×6 factorial design in the presence and absence of predator stress, induced concentration-dependent lethality in tadpoles. The 96-h LC50 for Roundup in the absence and presence of predator stress were 3.76mgae/L and 3.39mgae/L, respectively. The 10-day LC50 value for Roundup was significantly lower, 2.12mgae/L and 1.91mgae/L in the absence and presence of predator stress, respectively. Lower concentrations of Roundup (1, 2 and 3mgae/L) induced the formation of micronuclei (MN) in the erythrocytes of tadpoles at 24-h (F3,56=10.286, p<0.001), 48-h (F3,56=48.255, p<0.001), 72-h (F3,56=118.933, p<0.001) and 96-h (F3,56=85.414, p<0.001) in a concentration-dependent manner. Presence of predator stress apparently increased the toxicity and genotoxicity of Roundup; but these effects were not statistically significant. These findings suggest that Roundup at environmentally relevant concentrations has lethal and genotoxic impact on E. cyanophlyctis; which may have long-term fitness consequence to the species.

  6. Afobazole modifies the neurotoxic and genotoxic effects in rat prenatal alcoholization model.

    PubMed

    Shreder, E D; Shreder, O V; Zabrodina, V V; Durnev, A D; Seredenin, S B

    2014-08-01

    Prenatal ethanol leads to the formation of a wide spectrum of neurotoxic injuries to the brain in embryos by day 20 of intrauterine development. High levels of DNA aberrations and apoptotic comets were detected in tissues of 13-day embryos and placentas of rats receiving 40% ethanol orally (4 ml/kg) during gestation. The increase in the levels of DNA aberrations and apoptotic comets in the embryonic and placental tissues of alcoholic rats on day 13 of gestation correlated with the emergence of morphological abnormalities of the brain in the embryos on day 20 of intrauterine development. Afobazole (antimutagen) in doses of 1 and 10 mg/kg reduced the genotoxic effects of ethanol in embryonic and placental tissues and the relevant neurotoxic involvement of the brain. PMID:25110091

  7. Evaluation of genotoxic effects of oral exposure to aluminum oxide nanomaterials in rat bone marrow.

    PubMed

    Balasubramanyam, A; Sailaja, N; Mahboob, M; Rahman, M F; Misra, S; Hussain, Saber M; Grover, Paramjit

    2009-05-31

    Nanomaterials have novel properties and functions because of their small size. The unique nature of nanomaterials may be associated with potentially toxic effects. The aim of this study was to evaluate the in vivo genotoxicity of rats exposed with Aluminum oxide nanomaterials. Hence in the present study, the genotoxicity of Aluminum oxide nanomaterials (30 and 40 nm) and its bulk material was studied in bone marrow of female Wistar rats using chromosomal aberration and micronucleus assays. The rats were administered orally with the doses of 500, 1000 and 2000 mg/kg bw. Statistically significant genotoxicity was observed with Aluminum oxide 30 and 40 nm with micronucleus as well as chromosomal aberration assays. Significantly (p < 0.05 or p < 0.001) increased frequency of MN was observed with 1000 and 2000 mg/kg bw dose levels of Aluminum oxide 30 nm (9.4 +/- 1.87 and 15.2 +/- 2.3, respectively) and Aluminum oxide 40 nm (8.1 +/- 1.8 and 13.9 +/- 2.21, respectively) over control (2.5 +/- 0.7) at 30 h. Likewise, at 48 h sampling time a significant (p < 0.05 or p < 0.001) increase in frequency of MN was evident at 1000 and 2000 mg/kg bw dose levels of Aluminum oxide 30 nm (10.6 +/- 1.68 and 16.6 +/- 2.66, respectively) and Aluminum oxide 40 nm (9.0 +/- 1.38 and 14.7 +/- 1.68, respectively) compared to control (1.8 +/- 0.75). Significantly increased frequencies (p < 0.05 or p < 0.001) of chromosomal aberrations were observed with Aluminum oxide 30 nm (1000 and 2000 mg/kg bw) and Aluminum oxide 40 nm (2000 mg/kg bw) in comparison to control at 18 and 24 h. Further, since there is need for information on the toxicokinetics of nanomaterials, determination of these properties of the nanomaterials was carried out in different tissues, urine and feces using inductively coupled plasma mass spectrometry (ICP-MS). A significant size dependent accumulation of Aluminum oxide nanomaterials occurred in different tissues, urine and feces of rats as shown by ICP-MS data. The results

  8. Bone marrow mesenchymal stromal cells affect the cell cycle arrest effect of genotoxic agents on acute lymphocytic leukemia cells via p21 down-regulation.

    PubMed

    Zhang, Yiran; Hu, Kaimin; Hu, Yongxian; Liu, Lizhen; Wang, Binsheng; Huang, He

    2014-09-01

    The effect of bone marrow microenvironment on the cell cycle of acute lymphocytic leukemia (ALL) and the underlying mechanism has not been elucidated. In this study, we found that in normal condition, bone marrow mesenchymal stromal cells (BM-MSCs) had no significant effect on the cell cycle and apoptosis of ALL; in the condition when the cell cycle of ALL was blocked by genotoxic agents, BM-MSCs could increase the S-phase cell ratio and decrease the G2/M phase ratio of ALL. Besides, BM-MSCs could protect ALL cells from drug-induced apoptosis. Then, we proved that BM-MSCs affect the cell cycle arrest effect of genotoxic agents on ALL cells via p21 down-regulation. Moreover, our results indicated that activation of Wnt/β-catenin and Erk pathways might be involved in the BM-MSC-induced down-regulation of p21 in ALL cells. Targeting microenvironment-related signaling pathway may therefore be a potential novel approach for ALL therapy.

  9. Genotoxic Effects in Swimmers Exposed to Disinfection By-products in Indoor Swimming Pools

    PubMed Central

    Kogevinas, Manolis; Villanueva, Cristina M.; Font-Ribera, Laia; Liviac, Danae; Bustamante, Mariona; Espinoza, Felicidad; Nieuwenhuijsen, Mark J.; Espinosa, Aina; Fernandez, Pilar; DeMarini, David M.; Grimalt, Joan O.; Grummt, Tamara; Marcos, Ricard

    2010-01-01

    Background Exposure to disinfection by-products (DBPs) in drinking water has been associated with cancer risk. A recent study (Villanueva et al. 2007; Am J Epidemiol 165:148–156) found an increased bladder cancer risk among subjects attending swimming pools relative to those not attending. Objectives We evaluated adults who swam in chlorinated pools to determine whether exposure to DBPs in pool water is associated with biomarkers of genotoxicity. Methods We collected blood, urine, and exhaled air samples from 49 nonsmoking adult volunteers before and after they swam for 40 min in an indoor chlorinated pool. We estimated associations between the concentrations of four trihalomethanes (THMs) in exhaled breath and changes in micronuclei (MN) and DNA damage (comet assay) in peripheral blood lymphocytes before and 1 hr after swimming; urine mutagenicity (Ames assay) before and 2 hr after swimming; and MN in exfoliated urothelial cells before and 2 weeks after swimming. We also estimated associations and interactions with polymorphisms in genes related to DNA repair or to DBP metabolism. Results After swimming, the total concentration of the four THMs in exhaled breath was seven times higher than before swimming. The change in the frequency of micronucleated lymphocytes after swimming increased in association with higher exhaled concentrations of the brominated THMs (p = 0.03 for bromodichloromethane, p = 0.05 for chlorodibromomethane, p = 0.01 for bromoform) but not chloroform. Swimming was not associated with DNA damage detectable by the comet assay. Urine mutagenicity increased significantly after swimming, in association with the higher concentration of exhaled bromoform (p = 0.004). We found no significant associations with changes in micronucleated urothelial cells. Conclusions Our findings support potential genotoxic effects of exposure to DBPs from swimming pools. The positive health effects gained by swimming could be increased by reducing the potential health

  10. In vitro study of the cytotoxic and genotoxic effects of indomethacin-loaded Eudragit(®) L 100 nanocapsules.

    PubMed

    Froder, J G; Dupeyrón, D; Carvalho, J C T; Maistro, E L

    2016-01-01

    Indomethacin is a non-steroidal anti-inflammatory agent included in one of the most commonly used drug classes worldwide. The use of this drug results in certain side effects, including gastrointestinal complications. Therefore, there exists a need to develop better methods for the delivery of such drugs into the body, such as those employing nanoparticles. The aim of the present study was to evaluate the cytotoxic and genotoxic effects of indomethacin-loaded Eudragit(®) L 100 nanocapsules (NI; based on methacrylic acid and methyl methacrylate) on cells unable (lymphocytes) and able to metabolize drugs (HepG2 cells), using comet and cytokinesis-block micronucleus (CBMN) assays in vitro. Cells were exposed to NI at concentrations of 5, 10, 50, 125, 250, and 500 μg/mL. The comet assay showed that NI induced no significant DNA damage in either cell type at any of the concentrations tested. The CBMN test confirmed these results; however, the highest concentration of 500 μg/mL resulted in a small but statistically significant clastogenic/aneugenic effect in HepG2 cells. These findings should encourage the development of new investigations of this nanomaterial as a delivery vehicle for anti-inflammatory drugs, such as indomethacin. PMID:27525928

  11. Analysis of Genotoxic and Cytotoxic Responses Induced by Simulated Space Radiation Qualities by Use of Recombinant Bacteria Carrying a Dual-Function Dual-Reporter Construct

    NASA Astrophysics Data System (ADS)

    Baumstark-Khan, Christa; Hellweg, Christine; Zahoor, Ahmed; Testard, Isabelle; Reitz, Guenther

    Along with the long-term space exploration come various potential health risks due to unique physical factors of the space environment. Space radiation is one of the primary environmental hazards associated with space flight. In order to deal with space-related risk radiation exposure must be properly characterised and quantified, and biological effects of charged particles have to be analysed in ground based research, especially as astronauts are subjected to a differing radiation quality in space than they receive on Earth. For risk assessment, the mutagenic potential of the heavy ion component of the galactic cosmic radiation is of major concern for tumour induction as radiation late effects. The recombinant SWITCH test is based on TA1535 Salmonella typhimurium cells transformed with a dual-function dual-reporter vector harbouring (a) the genes for bioluminescence production from Photobacterium leiognathi under the control of a DNA-damage inducible promoter and (b) the gene for green fluorescent protein from the jellyfish Aequorea victoria under the control of a constitutive promoter. Suchlike genetically modified organism report on the presence of genotoxic conditions by dose dependent increase of bioluminescence induction and on the presence of cytotoxic conditions by dose dependent decrease in GFP fluorescence. By this, it is possible to analyse bacterial inactivation and mutation induction by ionizing radiation in parallel in the same cell within short time. Experiments with heavy ions have been performed with the SWITCH test at GANIL with the following accelerated heavy ions: 35 MeV/u (72 keV/µm) and 75 MeV/u (37 keV/µm) carbon, 95 MeV/u argon (377 keV/µm), 95 MeV/u neon (98 keV/µm), 75 MeV/u nickel (967 keV/µm) and 29 MeV/u lead (10238 keV/µm). The results obtained clearly show that the numbers of hits (particles per cm2 ) necessary to inactivate the bacteria (cytotoxicity) depend on LET. The higher the ionisation capacity of the accelerated ion, the

  12. Genotoxicity of phthalates.

    PubMed

    Erkekoglu, Pınar; Kocer-Gumusel, Belma

    2014-12-01

    Many of the environmental, occupational and industrial chemicals are able to generate reactive oxygen species (ROS) and cause oxidative stress. ROS may lead to genotoxicity, which is suggested to contribute to the pathophysiology of many human diseases, including inflammatory diseases and cancer. Phthalates are ubiquitous environmental chemicals and are well-known peroxisome proliferators (PPs) and endocrine disruptors. Several in vivo and in vitro studies have been conducted concerning the carcinogenic and mutagenic effects of phthalates. Di(2-ethylhexyl)-phthalate (DEHP) and several other phthalates are shown to be hepatocarcinogenic in rodents. The underlying factor in the hepatocarcinogenesis is suggested to be their ability to generate ROS and cause genotoxicity. Several methods, including chromosomal aberration test, Ames test, micronucleus assay and hypoxanthine guanine phosphoribosyl transferase (HPRT) mutation test and Comet assay, have been used to determine genotoxic properties of phthalates. Comet assay has been an important tool in the measurement of the genotoxic potential of many chemicals, including phthalates. In this review, we will mainly focus on the studies, which were conducted on the DNA damage caused by different phthalate esters and protection studies against the genotoxicity of these chemicals.

  13. Effect of O6-Alkylguanine-DNA Alkyltransferase on Genotoxicity of Epihalohydrins

    PubMed Central

    Kalapila, Aley G.; Loktionova, Natalia A.; Pegg, Anthony E.

    2010-01-01

    The effect of O6-alkylguanine-DNA alkyltransferase (AGT) on the toxicity and mutagenicity of epihalohydrins was studied. AGT is a DNA repair protein that protects cells from agents that produce genotoxic O6-alkylguanine lesions by transferring the alkyl group to an internal cysteine residue (Cys145 in human AGT) in a single-step. This cysteine acceptor site is highly reactive and epihalohydrins reacted readily with AGT at this site with a halide order of reactivity of Br > Cl > F. AGT expression in bacterial cells caused a very large increase in the mutagenicity and cytotoxicity of epibromohydrin. The mutations were almost all G:C to A:T transitions. Epichlorohydrin also augmented AGT-mediated mutagenesis but to a lesser extent than epibromohydrin. In vitro experiments showed that AGT was covalently cross-linked to DNA in the presence of epibromohydrin and that this conjugation occurred predominantly at Cys145, and to a smaller extent at Cys150, a less reactive residue also located within the active site pocket. Two pathways yielding the AGT-DNA adduct were found to occur. The predominant mechanism results in an AGT-epihalohydrin intermediate, which, facilitated by the DNA binding properties of AGT, then reacts covalently with DNA. The second pathway involves an initial reactive DNA-epihalohydrin intermediate that subsequently reacts with AGT. Our results show that the paradoxical AGT-mediated increase in genotoxicity which has previously been shown to occur with dihaloalkanes, butadiene diepoxide and nitrogen mustards, also occurs with epihalohydrins and is likely to contribute to their toxicity and mutagenicity. PMID:19472322

  14. Genotoxicity of poorly soluble particles.

    PubMed

    Schins, Roel P F; Knaapen, Ad M

    2007-01-01

    Poorly soluble particles such as TiO2, carbon black, and diesel exhaust particles have been evaluated for their genotoxicity using both in vitro and in vivo assays, since inhalation of these compounds by rats at high concentrations has been found to lead to tumor formation. Two principle modes of genotoxic action can be considered for particles, referred to as primary and secondary genotoxicity. Primary genotoxicity is defined as genetic damage elicited by particles in the absence of pulmonary inflammation, whereas secondary genotoxicity implies a pathway of genetic damage resulting from the oxidative DNA attack by reactive oxygen/nitrogen species (ROS/RNS), generated during particle-elicited inflammation. Conceptually, primary genotoxicity might operate via various mechanisms, such as the actions of ROS (e.g., as generated from reactive particle surfaces), or DNA-adduct formation by reactive metabolites of particle-associated organic compounds (e.g., polycyclic aromatic hydrocarbons). Currently available literature data, however, merely indicate that the tumorigenesis of poorly soluble particles involves a mechanism of secondary genotoxicity. However, further research is urgently required, since (1) causality between pulmonary inflammation and genotoxicity has not yet been established, and (2) effects of inflammation on fundamental DNA damage responses that orchestrate mutagenesis and carcinogenic outcome,that is, cell cycle arrest, DNA repair, proliferation, and apoptosis, are currently poorly understood. PMID:17886067

  15. Genotoxicity of swine effluents.

    PubMed

    Techio, V H; Stolberg, J; Kunz, A; Zanin, E; Perdomo, C C

    2011-01-01

    This study aimed at the investigation of genotoxic effects of swine effluents from different stages of a treatment system for swine wastes through bioassay of stamen hairs and micronuclei in Tradescantia (clone BNL 4430). No significant differences (p≥0.05) regarding the genic mutations were found in the bioassay of stamen hairs, independently of the effluent analysed. For the genotoxicity test with micronuclei, the plants exposed to raw wastes, to sludge, and to effluent of the biodigester have presented higher rates of chromosomal damages (micronuclei), with significant differences in relation to the control group and other effluent of the waste treatment system (p≤0.05). The association between the chemical parameters and the genotoxicity data have shown that the variables COD and TKN have presented significant correlation (p≤0.05) with the number of mutagenic events in the tetrads.

  16. Single-cell gel electrophoresis assay in the ten spotted live-bearer fish, Cnesterodon decemmaculatus (Jenyns, 1842), as bioassay for agrochemical-induced genotoxicity.

    PubMed

    Vera-Candioti, Josefina; Soloneski, Sonia; Larramendy, Marcelo L

    2013-12-01

    The ability of two 48 percent chlorpyrifos-based insecticides (Lorsban* 48E® and CPF Zamba®), two 50 percent pirimicarb-based insecticides (Aficida® and Patton Flow®), and two 48 percent glyphosate-based herbicides (Panzer® and Credit®) to induce DNA single-strand breaks in peripheral blood erythrocytes of Cnesterodon decemmaculatus (Jenyns, 1842) (Pisces, Poeciliidae) exposed under laboratory conditions was evaluated by the single-cell gel electrophoresis (SCGE) assay. In those fish exposed to Lorsban* 48E®, CPF Zamba®, Aficida®, Patton Flow®, Credit®, and Panzer®, a significant increase of the genetic damage was observed for all formulations regardless of the harvesting time. This genotoxic effect was achieved by an enhancement of Type II-IV comets and a concomitant decrease of Type 0-I comets over control values. A regression analysis revealed that the damage varied as a negative function of the exposure time in those Lorsban* 48E®- and Aficida®-treated fish. On the other hand, a positive correlation between damage increase and exposure time was achieved after Patton Flow® and Credit® treatment. Finally, no correlation was observed between increase in the genetic damage and exposure time after treatment with CPF Zamba® or Panzer®. These results highlight that all agrochemicals inflict primary genotoxic damage at the DNA level at sublethal concentrations, regardless of the exposure time of the aquatic organisms under study, at least within a period of 96 h of treatment. PMID:24011534

  17. Single-cell gel electrophoresis assay in the ten spotted live-bearer fish, Cnesterodon decemmaculatus (Jenyns, 1842), as bioassay for agrochemical-induced genotoxicity.

    PubMed

    Vera-Candioti, Josefina; Soloneski, Sonia; Larramendy, Marcelo L

    2013-12-01

    The ability of two 48 percent chlorpyrifos-based insecticides (Lorsban* 48E® and CPF Zamba®), two 50 percent pirimicarb-based insecticides (Aficida® and Patton Flow®), and two 48 percent glyphosate-based herbicides (Panzer® and Credit®) to induce DNA single-strand breaks in peripheral blood erythrocytes of Cnesterodon decemmaculatus (Jenyns, 1842) (Pisces, Poeciliidae) exposed under laboratory conditions was evaluated by the single-cell gel electrophoresis (SCGE) assay. In those fish exposed to Lorsban* 48E®, CPF Zamba®, Aficida®, Patton Flow®, Credit®, and Panzer®, a significant increase of the genetic damage was observed for all formulations regardless of the harvesting time. This genotoxic effect was achieved by an enhancement of Type II-IV comets and a concomitant decrease of Type 0-I comets over control values. A regression analysis revealed that the damage varied as a negative function of the exposure time in those Lorsban* 48E®- and Aficida®-treated fish. On the other hand, a positive correlation between damage increase and exposure time was achieved after Patton Flow® and Credit® treatment. Finally, no correlation was observed between increase in the genetic damage and exposure time after treatment with CPF Zamba® or Panzer®. These results highlight that all agrochemicals inflict primary genotoxic damage at the DNA level at sublethal concentrations, regardless of the exposure time of the aquatic organisms under study, at least within a period of 96 h of treatment.

  18. Assessment of the cytotoxic, genotoxic and mutagenic effects of the commercial black dye in Allium cepa cells before and after bacterial biodegradation treatment.

    PubMed

    Ventura-Camargo, Bruna de Campos; de Angelis, Dejanira de Franceschi; Marin-Morales, Maria Aparecida

    2016-10-01

    The present study evaluated the cytotoxic, genotoxic and mutagenic actions of different concentrations (50 and 200 μg/L) of BDCP (Black Dye Commercial Product) used by textile industries, before and after bacterial biodegradation, by the conventional staining cytogenetic technique and NOR-banding in Allium cepa cells. Differences in the chromosomal and nuclear aberrations and alterations in the number of nucleoli were observed in cells exposed to BDCP with and without the microbial treatment. The significant frequencies of chromosome and nuclear aberrations noted in the tests with bacterially biodegraded BDCP indicate that the metabolites generated by degradation are more genotoxic than the chemical itself. Losses of genetic material characterize a type of alteration that was mainly associated with the action of the original BDCP, whereas chromosome stickiness, nuclear buds and binucleated cells were the aberrations that were preferentially induced by BDCP metabolites after biodegradation. The significant frequencies of cell death observed in the tests with biodegraded BDCP also show the cytotoxic effects of the BDCP metabolites. The reduction in the total frequency of altered cells after the recovery treatments showed that the test organism A. cepa has the ability to recover from damage induced by BDCP and its metabolites after the exposure conditions are normalized. PMID:27441992

  19. An in vitro study on the genotoxic effect of substituted furans in cells transfected with human metabolizing enzymes: 2,5-dimethylfuran and furfuryl alcohol

    PubMed Central

    Huffman, Minor P.; Høie, Anja H.; Svendsen, Camilla; Brunborg, Gunnar; Murkovic, Michael; Glatt, Hansruedi; Husøy, Trine

    2016-01-01

    2,5-Dimethylfuran (DMF) and furfuryl alcohol (FFA) are two substituted furans that are formed during the processing of foods and have also been used as food flavorings. DMF and FFA are proposed to be bioactivated by human sulfotransferases (SULTs) which are not expressed in conventional cell lines used for genotoxicity testing. Therefore, in addition to the standard V79 cell line, we used a transfected V79 derived cell line co-expressing human cytochrome P450 (CYP) 2E1 and human SULT1A1 to assess the genotoxicity of DMF and FFA. The alkaline single cell gel electrophoresis (SCGE) assay was used to detect DNA damage in the form of single strand breaks and alkali-labile sites after exposure to DMF (0.5h; 0.5, 1, 1.5 or 2mM) or FFA (3h; 1, 3, 6 or 15mM). DMF induced DNA damage in V79 cells in a concentration-dependent manner irrespective of the expression of human CYP2E1 and SULT1A1. Almost no increase in the level of DNA damage was detected after exposure to FFA, except for a weak effect at the highest concentration in the transfected cell line. The results suggest that DNA damage in V79 cells from exposure to DMF detected by the alkaline SCGE assay is independent of human CYP2E1 and SULT1A1, and the genotoxic effect of FFA, as assessed by SCGE, is minimal in V79 cells. PMID:27226491

  20. An in vitro study on the genotoxic effect of substituted furans in cells transfected with human metabolizing enzymes: 2,5-dimethylfuran and furfuryl alcohol.

    PubMed

    Huffman, Minor P; Høie, Anja H; Svendsen, Camilla; Brunborg, Gunnar; Murkovic, Michael; Glatt, Hansruedi; Husøy, Trine

    2016-09-01

    2,5-Dimethylfuran (DMF) and furfuryl alcohol (FFA) are two substituted furans that are formed during the processing of foods and have also been used as food flavorings. DMF and FFA are proposed to be bioactivated by human sulfotransferases (SULTs) which are not expressed in conventional cell lines used for genotoxicity testing. Therefore, in addition to the standard V79 cell line, we used a transfected V79 derived cell line co-expressing human cytochrome P450 (CYP) 2E1 and human SULT1A1 to assess the genotoxicity of DMF and FFA. The alkaline single cell gel electrophoresis (SCGE) assay was used to detect DNA damage in the form of single strand breaks and alkali-labile sites after exposure to DMF (0.5h; 0.5, 1, 1.5 or 2mM) or FFA (3h; 1, 3, 6 or 15mM). DMF induced DNA damage in V79 cells in a concentration-dependent manner irrespective of the expression of human CYP2E1 and SULT1A1. Almost no increase in the level of DNA damage was detected after exposure to FFA, except for a weak effect at the highest concentration in the transfected cell line. The results suggest that DNA damage in V79 cells from exposure to DMF detected by the alkaline SCGE assay is independent of human CYP2E1 and SULT1A1, and the genotoxic effect of FFA, as assessed by SCGE, is minimal in V79 cells. PMID:27226491

  1. Lymphocyte Oxidative Stress/Genotoxic Effects Are Related to Serum IgG and IgA Levels in Coke Oven Workers

    PubMed Central

    Gao, Meili; Li, Yongfei; Zheng, Aqun; Xue, Xiaochang; Chen, Lan; Kong, Yu

    2014-01-01

    We investigated oxidative stress/genotoxic effects levels, immunoglobulin levels, polycyclic aromatic hydrocarbons (PAHs) levels exposed in 126 coke oven workers and in 78 control subjects, and evaluated the association between oxidative stress/genotoxic effects levels and immunoglobulin levels. Significant differences were observed in biomarkers, including 1-hydroxypyrene levels, employment time, percentages of alcohol drinkers, MDA, 8-OHdG levels, CTL levels and CTM, MN, CA frequency, and IgG, IgA levels between the control and exposed groups. Slightly higher 1-OHP levels in smoking users were observed. For the dose-response relationship of IgG, IgA, IgM, and IgE by 1-OHP, each one percentage increase in urinary 1-OHP generates a 0.109%, 0.472%, 0.051%, and 0.067% decrease in control group and generates a 0.312%, 0.538%, 0.062%, and 0.071% decrease in exposed group, respectively. Except for age, alcohol and smoking status, IgM, and IgE, a significant correlation in urinary 1-OHP and other biomarkers in the total population was observed. Additionally, a significant negative correlation in genotoxic/oxidative damage biomarkers of MDA, 8-OH-dG, CTL levels, and immunoglobins of IgG and IgA levels, especially in coke oven workers, was found. These data suggest that oxidative stress/DNA damage induced by PAHs may play a role in toxic responses for PAHs in immunological functions. PMID:25136686

  2. Evaluation of the co-genotoxic effects of 1800 MHz GSM radiofrequency exposure and a chemical mutagen in cultured human cells

    NASA Astrophysics Data System (ADS)

    Perrin, Anne; Freire, Maëlle; Bachelet, Christine; Collin, Alice; Levêque, Philippe; Pla, Simon; Debouzy, Jean-Claude

    2010-11-01

    We investigated the effect of a 1800 MHz radiofrequency GSM signal combined with a known chemical mutagen (4-nitroquinoline-N-oxide: 4NQO) on human THP1 cells. Comet and γ-H2AX assays were used to assess DNA damage. No heating of the cell cultures was noted during exposure (2 h). The exposure of cells to electromagnetic fields with SARs of 2 to 16 W/kg did not increase the DNA damage induced by 4NQO, whereas the number of DNA strand breaks increased with a temperature increase of at least 4 °C. In conclusion, no co-genotoxic effect of radiofrequency was found at levels of exposure that did not induce heating.

  3. Genotoxic Effects of Titanium Dioxide and Cerium Dioxide Nanoparticles in Human Respiratory Epithelial Cells

    EPA Science Inventory

    The nanomaterial industry has recently seen rapid growth, therefore, the risk assessment of human exposure to nanomaterials in consumer products is of paramount importance. The genotoxicity of nanomaterials is a fundamental aspect of hazard identification and regulatory guidance....

  4. METABOLISM, MICROFLORA EFFECTS, AND GENOTOXICITY IN HALOACETIC ACID-TREATED CULTURES OF RAT CECAL MICROBIOTA

    EPA Science Inventory

    Haloacetic acids are by-products of drinking water disinfection. Several compounds in this class are genotoxic and have been identified as rodent hepatocarcinogens. Enzymes produced by the normal intestinal bacteria can transform some promutagens and procarcinogens to their bio...

  5. Mechanisms of the genotoxicity of crocidolite asbestos in mammalian cells: implication from mutation patterns induced by reactive oxygen species.

    PubMed Central

    Xu, An; Zhou, Hongning; Yu, Dennis Zengliang; Hei, Tom K

    2002-01-01

    Asbestos is an important environmental carcinogen in the United States and remains the primary occupational concern in many developing countries; however, the underlying mechanisms of its genotoxicity are not known. We showed previously that asbestos is a potent gene and chromosomal mutagen in mammalian cells and that it induces mostly multilocus deletions. Furthermore, reactive oxygen species (ROS) are associated with the mutagenic process. To evaluate the contribution of ROS to the mutagenicity of asbestos, we examined their generation, particularly hydrogen peroxide, and compared the types of mutants induced by crocidolite fibers with those generated by H(2)O(2 )in human-hamster hybrid (A(L)) cells. Using confocal scanning microscopy together with the radical probe 5,6 -chloromethy-2,7 -dichlorodihydrofluorescein diacetate (CM-H(2)DCFDA), we found that asbestos induces a dose-dependent increase in the level of ROS among fiber-treated A(L) cells, which is suppressed by concurrent treatment with dimethyl sulfoxide. Using N-acetyl-3,7-dihydroxyphenoxazine (Amplex Red reagent) together with horseradish peroxidase, we further demonstrated that there was a dose-dependent induction of H(2)O(2) in crocidolite-treated A(L) cells. The amount of H(2)O(2 )induced by asbestos reached a plateau at a dose of 6 microg/cm(2). Concurrent treatment with catalase (1,000 U/mL) inhibited this induction by 7- to 8-fold. Mutation spectrum analysis showed that the types of CD59(-) mutants induced by crocidolite fibers were similar to those induced by equitoxic doses of H(2)O(2). These results provide direct evidence that the mutagenicity of asbestos is mediated by ROS in mammalian cells. PMID:12361925

  6. Comparison of cytotoxic and genotoxic effects of plutonium-239 alpha particles and mobile phone GSM 900 radiation in the Allium cepa test.

    PubMed

    Pesnya, Dmitry S; Romanovsky, Anton V

    2013-01-20

    The goal of this study was to compare the cytotoxic and genotoxic effects of plutonium-239 alpha particles and GSM 900 modulated mobile phone (model Sony Ericsson K550i) radiation in the Allium cepa test. Three groups of bulbs were exposed to mobile phone radiation during 0 (sham), 3 and 9h. A positive control group was treated during 20min with plutonium-239 alpha-radiation. Mitotic abnormalities, chromosome aberrations, micronuclei and mitotic index were analyzed. Exposure to alpha-radiation from plutonium-239 and exposure to modulated radiation from mobile phone during 3 and 9h significantly increased the mitotic index. GSM 900 mobile phone radiation as well as alpha-radiation from plutonium-239 induced both clastogenic and aneugenic effects. However, the aneugenic activity of mobile phone radiation was more pronounced. After 9h of exposure to mobile phone radiation, polyploid cells, three-groups metaphases, amitoses and some unspecified abnormalities were detected, which were not registered in the other experimental groups. Importantly, GSM 900 mobile phone radiation increased the mitotic index, the frequency of mitotic and chromosome abnormalities, and the micronucleus frequency in a time-dependent manner. Due to its sensitivity, the A. cepa test can be recommended as a useful cytogenetic assay to assess cytotoxic and genotoxic effects of radiofrequency electromagnetic fields.

  7. Vigna unguiculata modulates cholesterol induced cardiac markers, genotoxicity and gene expressions profile in an experimental rabbit model.

    PubMed

    Janeesh, P A; Abraham, Annie

    2013-04-25

    Vigna unguiculata (VU) leaves are edible and used as a leafy vegetable in cuisine from traditional times in India. This study was designed to investigate the cardioprotective effect of VU in cholesterol fed rabbits. The animals were randomly divided into 4 groups of 6 animals each and the experimental period was 3 months. Group I-ND [normal diet 40 g feed], Group II-ND + FVU [flavanoid fraction of Vigna unguiculata (150 mg kg (-1) per body weight)], Group III-ND + CH [cholesterol (400 mg)] and Group IV-ND + CH (400 mg) +FVU (150 mg kg(-1) per body weight). After the experimental period, animals were sacrificed and the various parameters, such as cardiac markers, toxicity parameters, genotoxicity and gene expression, were investigated. Cholesterol feeding causes a significant increase in the levels of cardiac marker enzymes, namely lactate dehydrogenase (LDH) and creatine phospokinase (CPK), atherogenic index, toxicity parameters like serum glutamate oxaloacetate transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) were elevated. Antioxidant enzyme levels were decreased, lipid peroxidation products in heart tissue and inflammatory markers, namely cyclooxygenase (COX2) and lipooxygenase (LOX15) in peripheral blood monocytes (PBMCs), were significantly increased. A genotoxicity study using a Comet assay and gene expression by reverse transcriptase-polymerase chain reaction (RT-PCR) of transforming growth factor-b1 (TGF-b1) and heme oxygenase-1 (HO-1) from heart tissue showed an altered expression in the disease group. The supplementation of the flavonoid fraction of Vigna unguiculata leaves (FVU) in the CH + FVU group caused the reversal of the above parameters and cardiotoxicity to near normal when compared with the CH group and FVU. This study revealed the cardioprotective nature of Vigna unguiculata in preventing cardiovascular diseases and this effect is attributed to the presence of antioxidants and the antihyperlipidemic properties of the

  8. Interplay between Smoking-induced Genotoxicity and Altered Signaling in Pancreatic Carcinogenesis

    PubMed Central

    Batra, Surinder K.

    2012-01-01

    Despite continuous research efforts directed at early diagnosis and treatment of pancreatic cancer (PC), the status of patients affected by this deadly malignancy remains dismal. Its notoriety with regard to lack of early diagnosis and resistance to the current chemotherapeutics is due to accumulating signaling abnormalities. Hoarding experimental and epidemiological evidences have established a direct correlation between cigarette smoking and PC risk. The cancer initiating/promoting nature of cigarette smoke can be attributed to its various constituents including nicotine, which is the major psychoactive component, and several other toxic constituents, such as nitrosamines, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, and polycyclic aromatic hydrocarbons. These predominant smoke-constituents initiate a series of oncogenic events facilitating epigenetic alterations, self-sufficiency in growth signals, evasion of apoptosis, sustained angiogenesis, and metastasis. A better understanding of the molecular mechanisms underpinning these events is crucial for the prevention and therapeutic intervention against PC. This review presents various interconnected signal transduction cascades, the smoking-mediated genotoxicity, and genetic polymorphisms influencing the susceptibility for smoking-mediated PC development by modulating pivotal biological aspects such as cell defense/tumor suppression, inflammation, DNA repair, as well as tobacco-carcinogen metabolization. Additionally, it provides a large perspective toward tumor biology and the therapeutic approaches against PC by targeting one or several steps of smoking-mediated signaling cascades. PMID:22623649

  9. Can the comet assay be used reliably to detect nanoparticle-induced genotoxicity?

    PubMed

    Karlsson, Hanna L; Di Bucchianico, Sebastiano; Collins, Andrew R; Dusinska, Maria

    2015-03-01

    The comet assay is a sensitive method to detect DNA strand breaks as well as oxidatively damaged DNA at the level of single cells. Today the assay is commonly used in nano-genotoxicology. In this review we critically discuss possible interactions between nanoparticles (NPs) and the comet assay. Concerns for such interactions have arisen from the occasional observation of NPs in the "comet head", which implies that NPs may be present while the assay is being performed. This could give rise to false positive or false negative results, depending on the type of comet assay endpoint and NP. For most NPs, an interaction that substantially impacts the comet assay results is unlikely. For photocatalytically active NPs such as TiO2 , on the other hand, exposure to light containing UV can lead to increased DNA damage. Samples should therefore not be exposed to such light. By comparing studies in which both the comet assay and the micronucleus assay have been used, a good consistency between the assays was found in general (69%); consistency was even higher when excluding studies on TiO2 NPs (81%). The strong consistency between the comet and micronucleus assays for a range of different NPs-even though the two tests measure different endpoints-implies that both can be trusted in assessing the genotoxicity of NPs, and that both could be useful in a standard battery of test methods.

  10. Assessment of genotoxic effects of boron on wheat (Triticum aestivum L.) and bean (Phaseolus vulgaris L.) by using RAPD analysis.

    PubMed

    Kekec, Guzin; Sakcali, M Serdal; Uzonur, Irem

    2010-06-01

    In boron-rich soils of Turkey, boron tolerant wheat (Triticum aestivum L.) and sensitive bean (Phaseolus vulgaris L.) are most widely cultivated crops. In this study they have been studied to elucidate the probable genotoxic effects of boron by using RAPD analysis. During the study, root and stem lengths have been measured and inhibitory rates (%) of root growth have been found to be significant, starting from 10 (13%) and 5 ppm (19%) for wheat and bean, respectively, which is in strong correlation with the root DNA alterations; RAPD variations starting from 100 ppm for wheat and 25 ppm for bean. The preliminary findings encourage the use of these tools in investigation of genotoxic effects of boron on wheat, bean and the other crops. PMID:20467724

  11. Genotoxic effects of the herbicide Roundup Transorb and its active ingredient glyphosate on the fish Prochilodus lineatus.

    PubMed

    Moreno, Natália Cestari; Sofia, Silvia Helena; Martinez, Claudia B R

    2014-01-01

    Roundup Transorb (RT) is a glyphosate-based herbicide and despite its wide use around the world there are few studies comparing the effects of the active ingredient with the formulated product. In this context the purpose of this study was to compare the genotoxicity of the active ingredient glyphosate with the formulated product RT in order to clarify whether the active ingredient and the surfactant of the RT formula may exert toxic effects on the DNA molecule in juveniles of fish Prochilodus lineatus. Erythrocytes and gill cells of fish exposed to glyphosate and to RT showed DNA damage scores significantly higher than control animals. These results revealed that both glyphosate itself and RT were genotoxic to gill cells and erythrocytes of P. lineatus, suggesting that their use should be carefully monitored considering their potential impact on tropical aquatic biota.

  12. The cytotoxicity and genotoxicity of soluble and particulate cobalt in human lung epithelial cells.

    PubMed

    Xie, Hong; Smith, Leah J; Holmes, Amie L; Zheng, Tongzhang; Pierce Wise, John

    2016-05-01

    Cobalt is a toxic metal used in various industrial applications leading to adverse lung effects by inhalation. Cobalt is considered a possible human carcinogen with the lung being a primary target. However, few studies have considered cobalt-induced toxicity in human lung cells, especially normal lung epithelial cells. Therefore, in this study, we sought to determine the cytotoxicity and genotoxicity of particulate and soluble cobalt in normal primary human lung epithelial cells. Cobalt oxide and cobalt chloride were used as representative particulate and soluble cobalt compounds, respectively. Exposure to both particulate and soluble cobalt induced a concentration-dependent increase in cytotoxicity, genotoxicity, and intracellular cobalt ion levels. Based on intracellular cobalt ion levels, we found that soluble and particulate cobalt induced similar cytotoxicity while soluble cobalt was more genotoxic than particulate cobalt. These data indicate that cobalt compounds are cytotoxic and genotoxic to human lung epithelial cells.

  13. Genotoxic effects of a particular mixture of acetamiprid and alpha-cypermethrin on chromosome aberration, sister chromatid exchange, and micronucleus formation in human peripheral blood lymphocytes.

    PubMed

    Kocaman, Ayşe Yavuz; Topaktaş, Mehmet

    2010-04-01

    The genotoxic effects of a particular mixture of acetamiprid (Acm, neonicotinoid insecticide) and alpha-cypermethrin (alpha-cyp, pyrethroid insecticide) on human peripheral lymphocytes were examined in vitro by chromosomal aberrations (CAs), sister chromatid exchange (SCE), and micronucleus (MN) tests. The human peripheral lymphocytes were treated with 12.5 + 2.5, 15 + 5, 17.5 + 7.5, and 20 + 10 microg/mL of Acm+alpha-cyp, respectively, for 24 and 48 h. The mixture of Acm+alpha-cyp induced the CAs and SCEs at all concentrations and treatment times when compared with both the control and solvent control and these increases were concentration-dependent in both treatment times. MN formation was significantly induced at 12.5 + 2.5, 15 + 5, 17.5 + 7.5, microg/mL of Acm+alpha-cyp when compared with both controls although these increases were not concentration-dependent. Binuclear cells could not be detected sufficiently in the highest concentration of the mixture (20 + 10 microg/mL) for both the 24- and 48-h treatment times. Mitotic index (MI), proliferation index (PI) and nuclear division index (NDI) significantly decreased because of the cytotoxic and cytostatic effects of the mixture, at all concentrations for two treatment periods. Significant decreases in MI and PI were concentration dependent at both treatment times. The decrease in NDI was also concentration-dependent at 48-h treatment period. In general, Acm+alpha-cyp inhibited nuclear division more than positive control, mitomycin C (MMC) and showed a higher cytostatic effect than MMC. Furthermore, in this article, the results of combined effects of Acm+alpha-cyp were compared with the results of single effects of Acm or alpha-cyp (Kocaman and Topaktas,2007,2009, respectively). In conclusion, the particular mixture of Acm+alpha-cyp synergistically induced the genotoxicity/cytotoxicity in human peripheral blood lymphocytes.

  14. Effect of Brazilian propolis (AF-08) on genotoxicity, cytotoxicity and clonogenic death of Chinese hamster ovary (CHO-K1) cells irradiated with (60)Co gamma-radiation.

    PubMed

    Santos, Geyza Spigoti; Tsutsumi, Shigetoshi; Vieira, Daniel Perez; Bartolini, Paolo; Okazaki, Kayo

    2014-03-01

    The present study was conducted in order to evaluate the effect of Brazilian propolis (AF-08; 5, 10, 15, 30, 50, 100, and 200μg/mL) in protecting CHO-K1 cells against genotoxic and cytotoxic damage and clonogenic death induced by (60)Co gamma-radiation (1.0, 2.0, 4.0, and 6.0Gy). For this purpose, three interlinked endpoints were analyzed: induction of DNA damage by use of the micronucleus (MN) test (genotoxic damage), cell viability by means of the MTS assay, and differential staining (cytotoxic damage) and clonogenic death via the colony-formation test (cytotoxic damage). The MN test revealed that propolis alone (5-100μg/mL) was not genotoxic up to 100μg/mL and that 30μg/mL of propolis reduced the radiation-induced DNA damage (∼56% reduction, p<0.05), exhibiting a radio-protective effect on irradiated CHO-K1 cells. On the other hand, analysis of cytotoxicity showed that a concentration of 50μg/mL presented a significant proliferative effect (p<0.001) when associated with radiation, decreasing the percentage of necrotic cells (p<0.01). No mediated cytotoxic effect was found, but the concentration of 200μg/mL was toxic when analyzed at 24 and 48h via the differential staining technique, but not at 72h after irradiation, analyzed with the MTS assay. Differential staining also showed that necrosis was the main death modality in irradiated cells and that apoptosis was induced only at the toxic concentration of propolis (200μg/mL). Concerning the clonogenic capacity, a concentration of 50μg/mL also exhibited a significant stimulating effect on cell proliferation (p<0.001), in agreement with the data from differential staining. Taken together, these data suggest that the use of propolis AF-08 for the prevention of the adverse effects of ionizing radiation is promising. Nevertheless, additional investigations are necessary for a better understanding of potential applications of propolis to improve human health.

  15. Evaluating the Effects of Bioremediation on Genotoxicity of Polycyclic Aromatic Hydrocarbon-Contaminated Soil Using Genetically Engineered, Higher Eukaryotic Cell Lines

    PubMed Central

    Hu, Jing; Nakamura, Jun; Richardson, Stephen D.; Aitken, Michael D.

    2012-01-01

    Bioremediation is one of the commonly applied remediation strategies at sites contaminated with polycyclic aromatic hydrocarbons (PAHs). However, remediation goals are typically based on removal of the target contaminants rather than on broader measures related to health risks. We investigated changes in the toxicity and genotoxicity of PAH-contaminated soil from a former manufactured-gas plant site before and after two simulated bioremediation processes: a sequencing batch bioreactor system and a continuous-flow column system. Toxicity and genotoxicity of the residues from solvent extracts of the soil were determined by the chicken DT40 B-lymphocyte isogenic cell line and its DNA-repair-deficient mutants. Although both bioremediation processes significantly removed PAHs from the contaminated soil (bioreactor 69% removal; column 84% removal), bioreactor treatment resulted in an increase in toxicity and genotoxicity over the course of a treatment cycle, whereas long-term column treatment resulted in a decrease in toxicity and genotoxicity. However, when screening with a battery of DT40 mutants for genotoxicity profiling, we found that column treatment induced DNA damage types that were not observed in untreated soil. Toxicity and genotoxicity bioassays can supplement chemical analysis-based risk assessment for contaminated soil when evaluating the efficacy of bioremediation. PMID:22443351

  16. Cytotoxic and genotoxic effects of water and sediment samples from gypsum mining area in channel catfish ovary (CCO) cells.

    PubMed

    Ternjej, Ivančica; Gaurina Srček, Višnja; Mihaljević, Zlatko; Kopjar, Nevenka

    2013-12-01

    Man-made activities such as mining generate certain amounts of metal contaminated wastes which can reach aquatic environment and cause the serious effects on different organisms and ecosystem. Chemical analysis of the environmental samples is the most direct approach to reveal their pollution status but it cannot always provide information on biological effects to different organisms, including fish. This study was aimed to investigate the in vitro cytotoxicity and genotoxicity of water and sediment samples from gypsum mining area using the channel catfish ovary (CCO) cell line. Results obtained by the WST-1 assay and alkaline comet assay revealed that exposure of CCO cells to the same concentrations of contaminated water and sediment samples caused significant decrease in cell viability and increased DNA damages. Chemical analysis of water and sediment samples showed that increased concentrations of strontium, aluminum and iron were mainly responsible for the observed cytotoxic and genotoxic effects in CCO cells. The study suggested that fish CCO cells could be useful biological test-system for water and sediment cytotoxicity and genotoxicity assessments.

  17. Effects of chronic exposure to benzalkonium chloride in Oncorhynchus mykiss: cholinergic neurotoxicity, oxidative stress, peroxidative damage and genotoxicity.

    PubMed

    Antunes, S C; Nunes, B; Rodrigues, S; Nunes, R; Fernandes, J; Correia, A T

    2016-07-01

    Benzalkonium chloride (BAC) is one of the most used conservatives in pharmaceutical preparations. However, its use is limited to a small set of external use formulations, due to its high toxicity. Benzalkonium chloride effects are related to the potential exertion of deleterious effects, mediated via oxidative stress and through interaction with membrane enzymes, leading to cellular damage. To address the ecotoxicity of this specific compound rainbow trouts were chronically exposed to BAC at environmental relevant concentrations (ranging from 0.100 to 1.050mg/L), and the biological response of cholinergic neurotoxicity, modulation of the antioxidant defense, phase II metabolism, lipid peroxidation and genotoxicity was studied. The obtained results showed a dual pattern of antioxidant response, with significant alterations in catalase activity (starting at 0.180mg/L), and lipid peroxidation, for intermediate (0.180 and 0.324mg/L) concentrations. No significant alterations occurred for glutathione-S-transferases activity. An unexpected increased of the acetylcholinesterase activity was also recorded for the individuals exposed to higher concentrations of BAC (starting at 0.180mg/L). Furthermore, exposure to BAC resulted in the establishment of genotoxic alterations, observable (for the specific case of the comet assay results) for all tested BAC concentrations. However, and considering that the oxidative response was not devisable, other mechanisms may be involved in the genotoxic effects reported here. PMID:27280532

  18. Co-cultivated damp building related microbes Streptomyces californicus and Stachybotrys chartarum induce immunotoxic and genotoxic responses via oxidative stress.

    PubMed

    Markkanen Penttinen, Piia; Pelkonen, Jukka; Tapanainen, Maija; Mäki-Paakkanen, Jorma; Jalava, Pasi I; Hirvonen, Maija-Riitta

    2009-08-01

    Oxidative stress has been proposed to be one mechanism behind the adverse health outcomes associated with living in a damp indoor environment. In the present study, the capability of damp building-related microbes Streptomyces californicus and Stachybotrys chartarum to induce oxidative stress was evaluated in vitro. In addition, the role of oxidative stress in provoking the detected cytotoxic, genotoxic, and inflammatory responses was studied by inhibiting the production of reactive oxygen species (ROS) using N-acetyl-l-cysteine (NAC). RAW264.7 macrophages were exposed in a dose- and time-dependent manner to the spores of co-cultivated S. californicus and S. chartarum, to their separately cultivated spore-mixture, or to the spores of these microbes alone. The intracellular peroxide production and cytotoxicity were measured by flow cytometric analysis, nitric oxide production was analyzed by the Griess method, DNA damage was determined by the comet assay, and cytokine production was measured by an immunochemical ELISA (enzyme-linked immunosorbent assay). All the studied microbial exposures triggered oxidative stress and subsequent cellular damage in RAW264.7 macrophages. The ROS scavenger, NAC, prevented growth arrest, apoptosis, DNA damage, and cytokine production induced by the co-culture since it reduced the intracellular level of ROS within macrophages. In contrast, the DNA damage and cell cycle arrest induced by the spores of S. californicus alone could not be prevented by NAC. Bioaerosol-induced oxidative stress in macrophages may be an important mechanism behind the frequent respiratory symptoms and diseases suffered by residents of moisture damaged buildings. Furthermore, microbial interactions during co-cultivation stimulate the production of highly toxic compound(s) which may significantly increase oxidative damage. PMID:19459771

  19. Genotoxicity of arsenical compounds.

    PubMed

    Gebel, T W

    2001-03-01

    With respect to global human health hazard, arsenic (As) is one of the most important environmental single substance toxicants. Currently, millions of people all over the world are exposed to the ubiquitous element in exposure levels leading to long-term toxicity, in particular cancer. Unfortunately, it has not been elucidated up to now how As mechanistically leads to the induction of neoplasia. Besides its tumorigenic potential, As has been shown to be genotoxic in a wide variety of different experimental set-ups and biological endpoints. In vitro, the element was shown to induce chromosomal mutagenicity like micronuclei, chromosome aberrations, and sister chromatid exchanges. It mainly acts clastogenic but also has an aneugenic potential. Instead, its potential to induce point mutations is very low in bacterial as well as in mammalian cell systems. However, in combined exposure with point mutagens in vitro, As was shown to enhance the frequency of chemical mutations in a synergistic manner. Additionally, As was shown to induce chromosome aberrations and micronuclei in vivo in experiments with mice. After long-term exposure to As-contaminated drinking water, the great majority of human biomonitoring studies found elevated frequencies of DNA lesions like micronuclei or chromosome aberrations. Respective occupational studies are few. Like it is the case for As carcinogenicity, it is not known through which mechanism the genotoxicity of As is mediated, although the data available indicate that As may act indirectly on DNA, i.e. via mechanisms like interference of regulation of DNA repair or integrity. Because of the indirect mode of action, it has been discussed as well that As's genotoxicity may underlie a sublinear dose-response relationship. However, various problems like non-standardized test systems and experimental variability make it impossible to prove such statement. Basically, to be able to improve risk assessment, it is of crucial importance to

  20. Genotoxic effects and LC50 value of NaOCl on Orthrias angorae (Steindachner 1897).

    PubMed

    Gül, Süleyman; Ozkan, Oktay; Nur, Gökhan; Aksu, Pinar

    2008-06-01

    Studies show that different organisms used as bio-indicators have indicated several genotoxic and mutagenic effects of disinfected waters. In this study, the 96 h LC(50 )mean value of NaOCl for Orthrias angorae was calculated to be 0.5509 mg/L. The results showed that NaOCl is highly toxic to O. angorae specimens. Statistical analysis demonstrated a significant increase in micronuclei after the induction of 0.5 mg/L NaOCl concentration after 36 h. The same increase has been reported for 0.37 and 0.5 mg/L NaOCl concentrations after 72 h. Even though the MN frequency of 0.37 mg/L was similar after 36 and 72 h, only 72 h micronuclei frequency was statistically significant. The 72 h MN frequency of the negative control group was smaller than 36 h MN frequency of the negative control group. This discrepancy has led to 72 h MN frequency being statistically significant. MN frequency of 0.25 mg/L NaOCl concentration was insignificant when compared to negative test groups. The benzene treatment also caused a significant increase (p < 0.01) in the frequency of micronucleated erythrocytes.

  1. Analytical in vitro approach for studying cyto- and genotoxic effects of particulate airborne material.

    PubMed

    Aufderheide, Michaela; Scheffler, Stefanie; Möhle, Niklas; Halter, Beat; Hochrainer, Dieter

    2011-12-01

    In the field of inhalation toxicology, progress in the development of in vitro methods and efficient exposure strategies now offers the implementation of cellular-based systems. These can be used to analyze the hazardous potency of airborne substances like gases, particles, and complex mixtures (combustion products). In addition, the regulatory authorities require the integration of such approaches to reduce or replace animal experiments. Although the animal experiment currently still has to provide the last proof of the toxicological potency and classification of a certain compound, in vitro testing is gaining more and more importance in toxicological considerations. This paper gives a brief characterization of the CULTEX® Radial Flow System exposure device, which allows the exposure of cultivated cells as well as bacteria under reproducible and stable conditions for studying cellular and genotoxic effects after the exposure at the air-liquid or air-agar interface, respectively. A commercial bronchial epithelial cell line (16HBE14o-) as well as Salmonella typhimurium tester strains were exposed to smoke of different research and commercial available cigarettes. A dose-dependent reduction of cell viability was found in the case of 16HBE14o- cells; S. typhimurium responded with a dose-dependent induction of revertants. The promising results recommend the integration of cellular studies in the field of inhalation toxicology and their regulatory acceptance by advancing appropriate validation studies.

  2. Cytotoxic, genotoxic and mutagenic effects of sewage sludge on Allium cepa.

    PubMed

    Corrêa Martins, Maria Nilza; de Souza, Victor Ventura; da Silva Souza, Tatiana

    2016-04-01

    The objective of this study was to ascertain the cytotoxic, genotoxic and mutagenic potential of sewage sludge using Allium cepa bioassay. Solubilized and crude sludge from two sewage treatment stations (STSs), herein named JM and M, were tested. In addition, sanitized, crude and solubilized sludge were also analyzed from STS M. The treatments showed positive response to phytotoxicity, cytotoxicity, genotoxicity and/or mutagenicity. Despite negative results for MN F1 (micronuclei counted in F1 root cells, derived from meristematic cells), the monitoring of genotoxic and mutagenic activities of sewage sludge are recommended because in agricultural areas this residue is applied in large scale and continuously. Based on our results we advise caution in the use of sewage sludge in agricultural soils. PMID:26841290

  3. Genotoxic effects of bitumen fumes in Big Blue transgenic rat lung.

    PubMed

    Bottin, Marie Claire; Gate, Laurent; Rihn, Bertrand; Micillino, Jean Claude; Nathalie, Monhoven; Martin, Aurélie; Nunge, Hervé; Morel, Georges; Wrobel, Richard; Ayi-Fanou, Lucie; Champmartin, Catherine; Keith, Gérard; Binet, Stéphane

    2006-04-11

    Road paving workers are exposed to bitumen fumes (CAS No. 8052-42-4), a complex mixture of volatile compounds and particles containing carcinogenic and non-carcinogenic polycyclic aromatic hydrocarbons. However, epidemiological and experimental animal studies failed to draw unambiguous conclusions concerning their toxicity. In order to gain better insights on their genotoxic potential, we used an experimental design able to generate bitumen fumes at road paving temperature (temperature: 170 degrees C, total particulate matter: 100mg/m3) and perform a nose-only exposure of Big Blue transgenic rodents 6h/day for five consecutive days. The mutagenic properties of bitumen fumes were determined by analyzing the mutation frequency and spectrum of the neutral reporter gene cII inserted into the rodent genome. We previously observed in mouse lung, that bitumen fumes did not induce an increase of cII mutants, a modification of the mutation spectrum, nor the formation of DNA adducts. Since DNA adducts were found in the lungs of rats exposed to asphalt fumes in similar conditions, we decided to carry out an analogous experiment with Big Blue rats. A DNA adduct was detected 3 and 30 days after the end of treatment suggesting that these genetic alterations were quite steady. Thirty days after exposure, the cII mutant frequency was similar in control and exposed rats. In addition, a slight but not significant modification of the mutation spectrum associated with an increase of G:C to T:A and A:T to C:G transversions was noticeable in the treated animals. Then, these data failed to demonstrate a pulmonary mutagenic potential for bitumen fumes generated at road paving temperature in our experimental conditions despite the presence of a DNA adduct. These results may provide information concerning the pulmonary mechanism of action of this aerosol and may contribute to the occupational health hazard assessment.

  4. Genotoxic and immunotoxic potential effects of selected psychotropic drugs and antibiotics on blue mussel (Mytilus edulis) hemocytes.

    PubMed

    Lacaze, Emilie; Pédelucq, Julie; Fortier, Marlène; Brousseau, Pauline; Auffret, Michel; Budzinski, Hélène; Fournier, Michel

    2015-07-01

    The potential toxicity of pharmaceuticals towards aquatic invertebrates is still poorly understood and sometimes controversial. This study aims to document the in vitro genotoxicity and immunotoxicity of psychotropic drugs and antibiotics on Mytilus edulis. Mussel hemocytes were exposed to fluoxetine, paroxetine, venlafaxine, carbamazepine, sulfamethoxazole, trimethoprim and erythromycin, at concentrations ranging from μg/L to mg/L. Paroxetine at 1.5 μg/L led to DNA damage while the same concentration of venlafaxine caused immunomodulation. Fluoxetine exposure resulted in genotoxicity, immunotoxicity and cytotoxicity. In the case of antibiotics, trimethoprim was genotoxic at 200 μg/L and immunotoxic at 20 mg/L whereas erythromycin elicited same detrimental effects at higher concentrations. DNA metabolism seems to be a highly sensitive target for psychotropic drugs and antibiotics. Furthermore, these compounds affect the immune system of bivalves, with varying intensity. This attests the relevance of these endpoints to assess the toxic mode of action of pharmaceuticals in the aquatic environment.

  5. Effect of CYP2E1 induction by ethanol on the immunotoxicity and genotoxicity of extended low-level benzene exposure.

    PubMed

    Daiker, D H; Shipp, B K; Schoenfeld, H A; Klimpel, G R; Witz, G; Moslen, M T; Ward, J B

    2000-02-11

    Potential additive effects of ethanol consumption, a common life-style factor, and low-level benzene exposure, a ubiquitous environmental pollutant, were investigated. Ethanol is a potent inducer of the cytochrome P-450 2E1 (CYP2E1) enzyme, which bioactivates benzene to metabolites with known genotoxicity and immunotoxicity. A liquid diet containing 4.1% ethanol was used to induce hepatic CYP2E1 activity by 4-fold in female CD-1 mice. Groups of ethanol-treated or pair-fed control mice were exposed to benzene or filtered air in inhalation chambers for 7 h/d, 5 d/wk for 6 or 11 wk. The initial experiment focused on immunotoxicity endpoints based on literature reports that ethanol enhances high-dose benzene effects on spleen, thymus, and bone marrow cellularity and on peripheral red blood cell (RBC) and white blood cell (WBC) counts. No statistically significant alterations were found in spleen lymphocyte cellularity, subtype profile, or function (mitogen-induced proliferation, cytokine production, or natural killer cell lytic activity) after 6 wk of ethanol diet, 0.44 ppm benzene exposure, or both. This observed absence of immunomodulation by ethanol alone, a potential confounding factor, further validates our previously established murine model of sustained CYP2E1 induction by dietary ethanol. Subsequent experiments involved a 10-fold higher benzene level for a longer time of 11 wk and focused on genotoxic endpoints in known target tissues. Bone marrow and spleen cells were evaluated for DNA-protein cross-links, a sensitive transient index of genetic damage, and spleen lymphocytes were monitored for hprt-mutant frequency, a biomarker of cumulative genetic insult. No treatment-associated changes in either genotoxic endpoint were detected in animals exposed to 4.4 ppm benzene for 6 or 11 wk with or without coexposure to ethanol. Thus, our observations suggest an absence of genetic toxicity in CD-1 mice exposed to environmentally relevant levels of benzene with or

  6. Modulation of hexavalent chromium-induced genotoxic damage in peripheral blood of mice by epigallocatechin-3-gallate (EGCG) and its relationship to the apoptotic activity.

    PubMed

    García-Rodríguez, María Del Carmen; Montaño-Rodríguez, Ana Rosa; Altamirano-Lozano, Mario Agustín

    2016-01-01

    This study was conducted to investigate the relationship between modulation of genotoxic damage and apoptotic activity in Hsd:ICR male mice treated with (-)-epigallocatechin-3-gallate (EGCG) and hexavalent chromium [Cr(VI)]. Four groups of 5 mice each were treated with (i) control vehicle only, (ii) EGCG (10 mg/kg) by gavage, (iii) Cr(VI) (20 mg/kg of CrO3) intraperitoneally (ip), and (iv) EGCG in addition to CrO3 (EGCG-CrO3). Genotoxic damage was evaluated by examining presence of micronucleated polychromatic erythrocytes (MN-PCE) obtained from peripheral blood of the caudal vein at 0, 24, 48, and 72 h after treatment. Induction of apoptosis and cell viability were assessed by differential acridine orange/ethidium bromide (AO/EB) staining. EGCG treatment produced no significant changes in frequency of MN-PCE. However, CrO3 treatment significantly increased number of MN-PCE at 24 and 48 h post injection. Treatment with EGCG prior to CrO3 injection decreased number of MN-PCE compared to CrO3 alone. The MN-PCE reduction was greater than when EGCG was administered ip. The frequency of early apoptotic cells was elevated at 48 h following EGCG, CrO3, or EGCG-CrO3 exposure, with highest levels observed in the combined treatment group, while the frequencies of late apoptotic cells and necrotic cells were increased only in EGCG-CrO3 exposure. Our findings support the view that EGCG is protective against genotoxic damage induced by Cr(VI) and that apoptosis may contribute to elimination of DNA-damaged cells (MN-PCE) when EGCG was administered prior to CrO3. Further, it was found that the route of administration of EGCG plays an important role in protection against CrO3-induced genotoxic damage.

  7. Modulation of hexavalent chromium-induced genotoxic damage in peripheral blood of mice by epigallocatechin-3-gallate (EGCG) and its relationship to the apoptotic activity.

    PubMed

    García-Rodríguez, María Del Carmen; Montaño-Rodríguez, Ana Rosa; Altamirano-Lozano, Mario Agustín

    2016-01-01

    This study was conducted to investigate the relationship between modulation of genotoxic damage and apoptotic activity in Hsd:ICR male mice treated with (-)-epigallocatechin-3-gallate (EGCG) and hexavalent chromium [Cr(VI)]. Four groups of 5 mice each were treated with (i) control vehicle only, (ii) EGCG (10 mg/kg) by gavage, (iii) Cr(VI) (20 mg/kg of CrO3) intraperitoneally (ip), and (iv) EGCG in addition to CrO3 (EGCG-CrO3). Genotoxic damage was evaluated by examining presence of micronucleated polychromatic erythrocytes (MN-PCE) obtained from peripheral blood of the caudal vein at 0, 24, 48, and 72 h after treatment. Induction of apoptosis and cell viability were assessed by differential acridine orange/ethidium bromide (AO/EB) staining. EGCG treatment produced no significant changes in frequency of MN-PCE. However, CrO3 treatment significantly increased number of MN-PCE at 24 and 48 h post injection. Treatment with EGCG prior to CrO3 injection decreased number of MN-PCE compared to CrO3 alone. The MN-PCE reduction was greater than when EGCG was administered ip. The frequency of early apoptotic cells was elevated at 48 h following EGCG, CrO3, or EGCG-CrO3 exposure, with highest levels observed in the combined treatment group, while the frequencies of late apoptotic cells and necrotic cells were increased only in EGCG-CrO3 exposure. Our findings support the view that EGCG is protective against genotoxic damage induced by Cr(VI) and that apoptosis may contribute to elimination of DNA-damaged cells (MN-PCE) when EGCG was administered prior to CrO3. Further, it was found that the route of administration of EGCG plays an important role in protection against CrO3-induced genotoxic damage. PMID:26713419

  8. Silver nanoparticles: correlating nanoparticle size and cellular uptake with genotoxicity

    PubMed Central

    Butler, Kimberly S.; Peeler, David J.; Casey, Brendan J.; Dair, Benita J.; Elespuru, Rosalie K.

    2015-01-01

    The focus of this research was to develop a better understanding of the pertinent physico-chemical properties of silver nanoparticles (AgNPs) that affect genotoxicity, specifically how cellular uptake influences a genotoxic cell response. The genotoxicity of AgNPs was assessed for three potential mechanisms: mutagenicity, clastogenicity and DNA strand-break-based DNA damage. Mutagenicity (reverse mutation assay) was assessed in five bacterial strains of Salmonella typhimurium and Echerichia coli, including TA102 that is sensitive to oxidative DNA damage. AgNPs of all sizes tested (10, 20, 50 and 100nm), along with silver nitrate (AgNO3), were negative for mutagenicity in bacteria. No AgNPs could be identified within the bacteria cells using transmission electron microscopy (TEM), indicating these bacteria lack the ability to actively uptake AgNPs 10nm or larger. Clastogenicity (flow cytometry-based micronucleus assay) and intermediate DNA damage (DNA strand breaks as measured in the Comet assay) were assessed in two mammalian white blood cell lines: Jurkat Clone E6-1 and THP-1. It was observed that micronucleus and Comet assay end points were inversely correlated with AgNP size, with smaller NPs inducing a more genotoxic response. TEM results indicated that AgNPs were confined within intracellular vesicles of mammalian cells and did not penetrate the nucleus. The genotoxicity test results and the effect of AgNO3 controls suggest that silver ions may be the primary, and perhaps only, cause of genotoxicity. Furthermore, since AgNO3 was not mutagenic in the gram-negative bacterial Ames strains tested, the lack of bacterial uptake of the AgNPs may not be the major reason for the lack of genotoxicity observed. PMID:25964273

  9. Beryllium: genotoxicity and carcinogenicity.

    PubMed

    Gordon, Terry; Bowser, Darlene

    2003-12-10

    Beryllium (Be) has physical-chemical properties, including low density and high tensile strength, which make it useful in the manufacture of products ranging from space shuttles to golf clubs. Despite its utility, a number of standard setting agencies have determined that beryllium is a carcinogen. Only a limited number of studies, however, have addressed the underlying mechanisms of the carcinogenicity and mutagenicity of beryllium. Importantly, mutation and chromosomal aberration assays have yielded somewhat contradictory results for beryllium compounds and whereas bacterial tests were largely negative, mammalian test systems showed evidence of beryllium-induced mutations, chromosomal aberrations, and cell transformation. Although inter-laboratory differences may play a role in the variability observed in genotoxicity assays, it is more likely that the different chemical forms of beryllium have a significant effect on mutagenicity and carcinogenicity. Because workers are predominantly exposed to airborne particles which are generated during the machining of beryllium metal, ceramics, or alloys, testing of the mechanisms of the mutagenic and carcinogenic activity of beryllium should be performed with relevant chemical forms of beryllium.

  10. A bioassessment of soil nickel genotoxic effect in orchard planted on rehabilitated coalmine overburden.

    PubMed

    Ličina, Vlado; Akšić, Milica Fotirić; Colić, Slavica; Zec, Gordan

    2013-12-01

    Environmental problems of non-rehabilitated overburden material are present in surrounding of open coal mines worldwide. Ecological restoration of this soil material usually deals with the improvement of its bad physico-chemical properties and its poor nutrient status, sometimes associated with heavy metal problems. Applied overburden restoration by planting orchard (1990) is assumed to be the first of its kind at opencast mines globally, so that present work was aimed at acquiring information about its efficiency of the applied measures concerning their possible use in agriculture. Various physical and chemical properties, together with the pseudo total and DTPA extractable metals (Fe, Mn, Cu, Zn, Co, Ni, Pb, Cr, Cd) as well as sequential Ni extraction analyses, was measured, in order to evaluate the impact of soil's Ni level (76.3-111.7 mg kg⁻¹) on decreasing yields of apples, pears and plums. As a general pattern, reclaimed soil was significantly enriched with organic matter (>2.5 percent) and nutrients compared to the initial (2 m depth) and non-reclaimed adjacent soil, approving this method for overburden restoration. Despite low Ni concentration in organs, Ni accumulation in a fruits' trees qualified these species as suitable for phytostabilization of present heavy metals, with a woody biomass as a large and important sink for Ni, especially in the roots. Applied cytogenetic studies evaluate the lack of genotoxic effect of nickel (Ni) on the gametic cells of investigated species, having no significant effect on meiosis and pollen germination. Most of the found anomalies were in apples, as a kind of aberrations with sticky figures and chromosome lagging, should be ascribed to the environmental and genetic interaction over the aging of trees.

  11. Cholinesterase-inhibiting and genotoxic effects of acute carbofuran intoxication in man: a case report.

    PubMed

    Zeljezic, Davor; Vrdoljak, Ana Lucic; Kopjar, Nevenka; Radic, Bozica; Milkovic Kraus, Sanja

    2008-10-01

    Carbofuran belongs to the group of N-methylcarbamate insecticides used for the control of soil-dwelling and foliar-feeding insects in various crops; its consumption totals approximately 20,000 tonnes per year. Although the neurological effects on human beings have been well documented, little is known on its impact on the genome. A 38-year-old, healthy male worker employed in a carbofuran production facility accidentally inhaled the dust of the active ingredient carbofuran. Thirty minutes later, he experienced weakness, fatigue, perspiration, breathing difficulties, cephalalgia, disorientation, abdominal pain and vomiting. Blood samples were taken to measure cholinesterase activity, and to perform the alkaline comet assay and micronucleus assay combined with pancentromeric probes. Analyses were repeated 72 hr after intoxication and compared with the results obtained from regular monitoring conducted 10 days prior to the accident. Cholinesterase activity showed the highest correlation with the number of apoptotic cells, comet assay tail length, and number of long-tailed nuclei, suggesting that these are the genomic end-points primarily affected by carbofuran intake. Only a weak correlation was detected for the total number of micronuclei, centromere-containing micronuclei and nuclear buds. Since those end-points increased significantly 72 hr after the accident, they could be considered as late biomarkers of the effects of carbofuran intoxication. The results of this report suggest that, in the interests of higher standards in risk assessment and health hazard protection, periodical medical examination of carbamate-exposed populations should include genotoxicity testing in addition to the assessment of cholinesterase activity.

  12. Genotoxicity of phytoestrogens.

    PubMed

    Stopper, H; Schmitt, E; Kobras, K

    2005-07-01

    Plant extracts containing phytohormones are very popular as 'alternative' medicine for many kinds of diseases. They are especially favored by women who enter menopause and are concerned about the side effects of hormone replacement therapy. However, adverse health effects of phytoestrogens have often been ignored. This review examines the literature on genotoxicity and apoptotic effects of phytohormones. Genistein, coumestrol, quercetin, zearalenone, and resveratrol exerted genotoxic effects in in vitro test systems. Other phytoestrogens such as lignans, the isoflavones daidzein and glycetein, anthocyanidins, and the flavonol fisetin exhibited only weak or no effects in vitro. However, some metabolites of daidzein showed a genotoxic activity in vitro. Practically all of the phytoestrogens exhibit pro-apoptotic effects in some cell systems. Further investigations regarding dose-response-relationships and other aspects relevant for extrapolation to human exposure seem necessary. Until then, care may be advised in taking concentrated phytohormones. Nevertheless, the intake of substantial amounts of plant-food in a normal diet constitutes an important, individual contribution to cancer prevention.

  13. In vivo genotoxic effects of industrial waste leachates in mice following oral exposure.

    PubMed

    Chandra, Saurabh; Chauhan, Lalit K S; Dhawan, Alok; Murthy, Ramesh C; Gupta, Shrawan K

    2006-06-01

    Contamination of ground water by industrial waste poses potential health hazards for man and his environment. The improper disposal of toxic wastes could allow genotoxic chemicals to percolate into ground waters, and these contaminated ground waters may produce toxicity, including mutation and eventually cancer, in exposed individuals. In the present study, we evaluated the in vivo genotoxic potential of leachates made from three different kinds of industrial waste (tannery waste, metal-based waste, and waste containing dyes and pigments) that are disposed of in areas adjoining human habitation. Three different doses of test leachates were administered by oral gavage for 15 consecutive days to Swiss albino mice; their bone marrow cells were examined for chromosome aberrations (CAs), micronucleated polychromatic erythrocytes (MNPCEs), and DNA damage using the alkaline Comet assay. Exposure to the leachates resulted in significant (P < 0.05 or P < 0.001) dose-dependent increases in chromosome and DNA damage. Fragmented chromosomes and chromatid breaks were the major CAs observed. Chemical analysis of the leachates indicated that chromium and nickel were elevated above the limits established by health organizations. The highest levels of genotoxicity were produced by the metal-based leachate and the tannery-waste leachate, while the dye-waste leachate produced weaker genotoxic responses. The cytogenetic abnormalities and DNA damage produced by the leachates indicate that humans consuming water contaminated with these materials are at increased risk of developing adverse health consequences.

  14. Exposing native cyprinid (Barbus plebejus) juveniles to river sediments leads to gonadal alterations, genotoxic effects and thyroid disruption.

    PubMed

    Viganò, Luigi; De Flora, Silvio; Gobbi, Marco; Guiso, Giovanna; Izzotti, Alberto; Mandich, Alberta; Mascolo, Giuseppe; Roscioli, Claudio

    2015-12-01

    Juveniles (50 days post hatch) of a native cyprinid fish (Barbus plebejus) were exposed for 7 months to sediments from the River Lambro, a polluted tributary impairing the quality of the River Po for tens of kilometers from their confluence. Sediments were collected upstream of the city of Milan and downstream at the closure of the drainage basin of the River Lambro. Chemical analyses revealed the presence of a complex mixture of bioavailable endocrine-active chemicals, with higher exposure levels in the downstream section of the tributary. Mainly characterized by brominated flame retardants, alkylphenols, polychlorinated biphenyls, and minor co-occurring personal care products and natural hormones, the sediment contamination induced reproductive disorders, as well as other forms of endocrine disruption and toxicity. In particular, exposed male barbel exhibited higher biliary PAH-like metabolites, overexpression of the cyp1a gene, vitellogenin production in all specimens, the presence of oocytes (up to 22% intersex), degenerative alterations in their testis, liver fat vacuolization, a marked depression of total thyroxine (T4) and triiodothyronine (T3) plasma levels, and genotoxic damages determined as hepatic DNA adducts. These results clearly demonstrate that Lambro sediments alone are responsible for recognizable changes in the structure and function of the reproductive and, in general, the endocrine system of a native fish species. In the real environment, exposure to waterborne and food-web sources of chemicals are responsible for additional toxic loads, and the present findings thus provide evidence for a causal role of this tributary in the severe decline observed in barbel in recent decades and raise concern that the fish community of the River Po is exposed to endocrine-mediated health effects along tens of kilometres of its course. PMID:26580918

  15. Role of recombinant human erythropoietin loading chitosan-tripolyphosphate nanoparticles in busulfan-induced genotoxicity: Analysis of DNA fragmentation via comet assay in cultured HepG2 cells.

    PubMed

    Ghassemi-Barghi, Nasrin; Varshosaz, Jaleh; Etebari, Mahmoud; Jafarian Dehkordi, Abbas

    2016-10-01

    Busulfan is one of the most effective chemotherapeutic agents used for the treatment of chronic myeloid leukemia. Busulfan is involved in secondary malignancy due to its genotoxic potential in normal tissues. As an alkylating agent busulfan can cause DNA damage by cross-linking DNAs and DNA and proteins, induces senescence in normal cells via transient depletion of intracellular glutathione (GSH) and subsequently by a continuous increase in reactive oxygen species (ROS) production. Erythropoietin, a glycoprotein widely used against drug induced anemia in cancerous patients and regulates hematopoiesis, has been shown to exert an important cyto-protective effect in many tissues. Recombinant human erythropoietin has been demonstrated to directly limit cell injury and ROS generation during oxidative stress. Furthermore, rhEPO decreased levels of pro-apoptotic factor (Bax) and also increased expression of the anti-apoptotic factor Bcl2. According to EPO's short half-life and requirements for the frequently administration, finding the new strategies to attenuate its side effects is important. The aim of this study was to explore whether rhEPO loading chitosan-tripolyphosphate nanoparticles protects against busulfan-induced genotoxicity in HepG2 cells. For this purpose cells were incubated with busulfan alone, regular rhEPO alone and regular rhEPO and CS-TPP-EPO nanoparticles along with busulfan in pre and co-treatment condition. Our results showed that busulfan induced a noticeable genotoxic effects in HepG2 cells (p<0.0001). Both regular rhEPO and CS-TPP-EPO nanoparticles reduced the effects of busulfan significantly (p<0.0001) by reduction of the level of DNA damage via blocking ROS generation, and enhancement intracellular glutathione levels. CS-TPP-EPO nanoparticles were more effective than regular rhEPO in both pre and co-treatment conditions. In conclusion, our results show that administration of rhEPO and CS-TPP-EPO nanoparticles especially in the pre

  16. 7,12-Dimethylbenz(a)anthracene-induced genotoxicity on bone marrow cells from mice phenotypically selected for low acute inflammatory response.

    PubMed

    Katz, Iana Suly Santos; Albuquerque, Layra Lucy; Suppa, Alessandra Paes; da Silva, Graziela Batista; Jensen, José Ricardo; Borrego, Andrea; Massa, Solange; Starobinas, Nancy; Cabrera, Wafa Hanna Koury; De Franco, Marcelo; Borelli, Primavera; Ibañez, Olga Martinez; Ribeiro, Orlando Garcia

    2016-01-01

    Exposure to polycyclic aromatic hydrocarbon (PAH) environmental contaminants has been associated with the development of mutations and cancer. 7,12-Dimethylbenz(a)anthracene ( DMBA), a genotoxic agent, reacts with DNA directly, inducing p53-dependent cytotoxicity resulting in cell death by apoptosis or giving rise to cancer. DMBA metabolism largely depends on activation of the aryl hydrocarbon receptor (AhR). Mice phenotypically selected for high (AIRmax) or low (AIRmin) acute inflammatory response present a complete segregation of Ahr alleles endowed with low (Ahr(d)) or high (Ahr(b1)) affinity to PAHs, respectively. To evaluate the role of AhR genetic polymorphism on the bone marrow susceptibility to DMBA, AIRmax and AIRmin mice were treated with a single intraperitoneal injection of DMBA (50mg/kg b.w.) in olive oil. Bone marrow cells (BMCs) were phenotyped by both flow cytometry and cytoslide preparations. Despite a significant decrease in total cell count in BM from AIRmin mice, there was an increase of blast cells and immature neutrophils at 1 and 50 days after DMBA treatment, probably due to a cell-cycle blockade at the G1/S transition leading to immature stage cell production. A panel of proteins related to cell cycle regulation was evaluated in immature BM cells (Lin(-)) by Western Blot, and DNA damage and repair were measured using an alkaline version of the Comet assay. In Lin(-) cells isolated from AIRmin mice, high levels were found in both p53 and p21 protein contents in contrast with the low levels of CDK4 and Ciclin D1. Evaluation of DNA repair in DMBA-treated BMCs, indicated long-lasting genotoxicity and cytotoxicity in BMC from AIRmin mice and a blockade of cell cycle progression. On the other hand, AIRmax mice have a high capacity of DNA damage repair and protection. These mechanisms can be associated with the differential susceptibility to the toxic and carcinogenic effects of DMBA observed in these mice. PMID:26687588

  17. Genotoxic effects of 1 GeV/amu Fe ions in mouse kidney epithelial cells

    NASA Astrophysics Data System (ADS)

    Kronenberg, A.; Gauny, S. S.; Connolly, L.; Turker, M.

    Human exploration of space places individuals in environments where they are exposed to charged particle radiation. The goal of our studies is to assess the genotoxic and mutagenic effects of high energy Fe ions (1 GeV/amu) in kidney epithelial cells of the mouse irradiated either in vitro or in vivo. The initial study focused on establishing the toxicity of these heavy ions (LET=159 keV/micron) in two Aprt heterozygous kidney epithelial cell lines: K06 cells derived from a C57BL6/129Sv animal, and clone 4a cells derived from a C57BL6/DBA2 animal. Cells were exposed in vitro to graded doses of Fe ions (0-300 cGy) and the toxicity of the treatment was established using colony forming assays. Experiments were performed in triplicate at the NASA Space Radiation Laboratory at Brookhaven National Laboratory. The results indicate that Fe ions are toxic to mouse kidney epithelial cells and that no shoulder is observed on the survival curve for cells from either genetic background. The clone 4a cells were more sensitive to Fe ion exposures than the K06 cells. The D(37) for clone 4a cells was 92 cGy and the D(10) was 212 cGy. The more resistant K06 cells had a D(37) of 192 cGy and an estimated D(10) of 388 cGy. Parallel experiments are underway to establish the RBE's for cell killing for these two cell lines. Supported by NASA grant T-403X to A. Kronenberg

  18. Evaluation of the genotoxic effects of a folk medicine, Petiveria alliacea (Anamu).

    PubMed

    Hoyos, L S; Au, W W; Heo, M Y; Morris, D L; Legator, M S

    1992-07-01

    Crude extract from a plant known as Petiveria alliacea (Anamu) is used extensively as folk medicine in developing countries like Colombia, South America. Although the plant is known to contain toxic ingredients potential adverse health effects from its use have not been adequately evaluated. We investigated its genotoxic activities by conducting a sister chromatid exchange (SCE) assay using cells in vitro and in vivo. Lymphocytes from humans were treated at 24 h after initiation of culture for 6 h with alcohol extract from the folk medicine. Concentrations of 0, 10, 100, 250, 275, 500, 750, and 1000 micrograms/ml of the extract were used. Significant dose-dependent increase of SCE (3.7-7.4 SCE per cell) were observed (analysis of variances, p less than 0.01). Delay in cell proliferation but not inhibition of mitosis was also observed. In another experiment, mice were exposed once orally to 1x, 200x, 300x and 400x the human daily consumption dose of Anamu. The induction of sister chromatid exchanges in bone marrow cells were investigated. We observed a significant dose dependent increase of SCE compared with the saline control (2.15-4.53; p less than 0.01) and compared with the solvent control (3.04-4.53; p less than 0.01). Our data suggest, therefore, that the folk medicine contains mutagenic and potentially carcinogenic agents although the medicine is not a potent mutagen. Individuals who consume large amounts of this drug may be at risk for development of health problems. Further studies with cells from exposed individuals and from experimental animals should be conducted to provide a better evaluation of health risk from the use of this drug.

  19. Relationship between genotoxic effects of breast cancer treatments and patient basal DNA integrity.

    PubMed

    Ceballos, María Paula; Funes, Juan Capitaine; Massa, Estefanía; Cipulli, Germán; Gil, Alfonso Benitez; Funes, Carlos Capitaine; Tozzini, Roberto; Ghersevich, Sergio

    2014-01-01

    Radiotherapy and chemotherapy cause genotoxic side effects that are highly variable among patients. In this study, we evaluated DNA integrity using the comet assay in peripheral blood lymphocytes from breast cancer patients before ("pre-treatment patients"; n=47) and after ("post-treatment patients"; n=24) radiotherapy and/or chemotherapy treatment and from healthy donors (n=15). Comet evaluation was made by visual (types 0-4) and digital (percentage of DNA remaining in the comet head=% head DNA) analysis. The association between the level of DNA damage and cancer prognostic factors was assessed. The treatments caused a significant increase in DNA damage registered by both visual (p<0.001) and digital (p<0.001) analyses. No significant associations between the level of DNA damage in pre-treatment patients and cancer prognostic factors were found. A significant correlation between the comet results from each patient before and after treatment (r=0.64, p=0.001) was observed. The % head DNA in post-treatment samples from patients with a high level of DNA damage before treatment (30.3±3.1%, p<0.01) was lower than in post-treatment samples from patients with a low-to-medium level of DNA damage before therapy (49.2±4.4%). These results support the usefulness of the comet assay as a sensitive technique to evaluate basal DNA status and DNA damage caused by cancer treatments. The comet assay could contribute to treatment decisions, especially by taking into account the patient's basal DNA damage before therapy.

  20. Flow-cytometric determination of genotoxic effects of exposure to petroleum in mink and sea otters

    USGS Publications Warehouse

    Bickham, J.W.; Mazet, J.A.; Blake, J.; Smolen, M.J.; Lou, Y.; Ballachey, B.E.

    1998-01-01

    Three experiments were conducted to investigate the genotoxic effects of crude oil on mink and sea otters, In the first experiment, the effects on mink of chronic exposure to weathered Prudhoe Bay crude oil were studied, Female mink were fed a diet that included weathered crude oil for a period of 3 weeks prior to mating, during pregnancy and until weaning. Kits were exposed through lactation and by diet after weaning until 4 months of age. Kidney and liver tissues of the kits were examined using flow cytometry (FCM) and it was found that the genome size was increased in kidney samples from the experimental group compared to the control group. This effect was probably due to some type of DNA amplification and it could have been inherited from the exposed mothers or have been a somatic response to oil exposure in the pups, No evidence of clastogenic effects, as measured by the coefficient of variation (CV) of the G(1) peak, was found in kidney or liver tissue. In the second experiment, yearling female mink were exposed either by diet or externally to crude oil or bunker C fuel oil. Evidence for clastogenic damage was found in spleen tissue for the exposure groups, but not in kidney tissue. No evidence of increased genome size was observed. In the third experiment, blood was obtained from wild-caught sea otters in Prince William Sound. The sea otters represented two populations: one from western Prince William Sound that was potentially exposed to oil from the Exxon Valdez oil spill and a reference population from eastern Prince William Sound that did not receive oil from the spill. The spill had occurred 1.5 years prior to obtaining the blood samples. Although the mean CVs did not differ between the populations, the exposed population had a significantly higher variance of CV measurements and five out of 15 animals from the exposed population had CVs higher than the 95% confidence limits of the reference population, It is concluded that FCM is a sensitive indicator

  1. Flooding modifies the genotoxic effects of pollution on a worm, a mussel and two fish species from the Sava River.

    PubMed

    Aborgiba, Mustafa; Kostić, Jovana; Kolarević, Stoimir; Kračun-Kolarević, Margareta; Elbahi, Samia; Knežević-Vukčević, Jelena; Lenhardt, Mirjana; Paunović, Momir; Gačić, Zoran; Vuković-Gačić, Branka

    2016-01-01

    Extreme hydrological events, such as water scarcity and flooding, can modify the effect of other stressors present in aquatic environment, which could result in the significant changes in the ecosystem functioning. Presence and interaction of various stressors (genotoxic pollutants) in the environment can influence the integrity of DNA molecules in aquatic organisms which can be negatively reflected on the individual, population and community levels. Therefore, in this study we have investigated the impact of flooding, in terms of genotoxicity, on organisms belonging to different trophic levels. The study was carried out on the site situated in the lower stretch of the Sava River which faced devastating effects of severe flooding in May 2014. The flooding occurred during our field experiment and this event provided a unique opportunity to assess its influence to the environment. The in situ effects of this specific situation were monitored by measuring physical, chemical and microbiological parameters of water, and by comparing the level of DNA damage in coelomocytes and haemocytes of freshwater worms Branchiura sowerbyi, haemocytes of freshwater mussels Unio tumidus and blood cells of freshwater fish Abramis bjoerkna/Abramis sapa, by means of the comet assay. Our study indicated that the flooding had a significant impact on water quality by decreasing the amount and discharge rate of urban wastewaters but simultaneously introducing contaminants from the nearby fly ash disposal field into river by runoff, which had diverse effects on the level of DNA damage in the studied organisms. This indicates that the assessment of genotoxic pollution in situ is strongly affected by the choice of the bioindicator organism.

  2. Evaluation of the cytotoxicity, genotoxicity and apoptotic induction of an aqueous extract of Achyrocline satureioides (Lam.) DC.

    PubMed

    Sabini, M C; Cariddi, L N; Escobar, F M; Mañas, F; Comini, L; Reinoso, E; Sutil, S B; Acosta, A C; Núñez Montoya, S; Contigiani, M S; Zanon, S M; Sabini, L I

    2013-10-01

    Achyrocline satureioides is widely consumed as infusion or aperitif and shows important therapeutic properties. Previously, we reported absence of genotoxicity of cold aqueous extract (CAE) of A. satureioides by Allium test. However, one test cannot predict the genotoxic effects of a substance. Thus, the aim of this work was to investigate cytotoxicity, genotoxicity and apoptotic ability of CAE of A. satureioides. In addition, CAE was chemically characterized. The cytotoxicity was evaluated by Trypan blue and MTT assays. The apoptotic capacity was evaluated by Hoechst staining and DNA fragmentation-analysis. The genotoxicity was studied by comet assay (CA) and micronucleus test. The identification and quantification of flavonoids were performed by HPLC-ESI-MS/MS. The cytotoxicity studies indicated low toxicity of CAE. In addition, CAE did not induce apoptotic effects on human PBMCs. CAE did not show genotoxicity in vitro against Vero cells, at 10-50 μg/mL. CAE did not induce in vivo genotoxic effects, but it showed at high concentrations cytotoxicity by micronucleus assay. CAE presented flavonoids such as quercetin, 3-O-methylquercetin and luteolin. In conclusion, A. satureioides at popularly concentrations used, in aperitif or infusion, can be consumed safely because did not show any cytotoxic or genotoxic effects.

  3. Illicit drugs as new environmental pollutants: cyto-genotoxic effects of cocaine on the biological model Dreissena polymorpha.

    PubMed

    Binelli, A; Pedriali, A; Riva, C; Parolini, M

    2012-03-01

    The increase in global consumption of illicit drugs has produced not only social and medical problems but also a potential new environmental danger. Indeed, it has been established that drugs consumed by humans end up in surface waters, after being carried through the sewage system. Although many studies to measure concentrations of several drugs of abuse in freshwater worldwide have been conducted, no data have been available to evaluate their potentially harmful effects on non-target organisms until now. The present study represents the first attempt to investigate the cyto-genotoxic effects of cocaine, one of the primary drugs consumed in Western Countries, in the biological model Dreissena polymorpha by the use of a biomarker battery. We performed the following tests on Zebra mussel hemocytes: the single cell gel electrophoresis (SCGE) assay, the apoptosis frequency evaluation and the micronucleus assay (MN test) for the evaluation of genotoxicity and the lysosomal membranes stability test (neutral red retention assay; NRRA) to identify the cocaine cytotoxicity. We exposed the molluscs for 96 h to three different nominal concentrations in water (40 ng L(-1); 220 ng L(-1); and 10 μg L(-1)). Cocaine caused significant (p<0.05) primary DNA damage in this short-term experiment, but it also caused a clear increase in micronucleated cells and a marked rise in apoptosis, which was evident in samples from even the lowest environmental cocaine concentration. Because cocaine decreased the stability of lysosomal membranes, we also highlighted its cytotoxicity and the possible implications of oxidative stress for the observed genotoxic effects. PMID:22119280

  4. Genotoxic and hematological effects in children exposed to a chemical mixture in a petrochemical area in Mexico.

    PubMed

    Pelallo-Martínez, Nadia Azenet; Batres-Esquivel, Lilia; Carrizales-Yáñez, Leticia; Díaz-Barriga, Fernando Martínez

    2014-07-01

    Children living in Coatzacoalcos, Veracruz, and in nearby surrounding areas are exposed to a mixture of pollutants from different sources. Previous studies in the area have reported genotoxic and haematotoxic compounds, such as lead (Pb), benzene, toluene, and polycyclic aromatic hydrocarbons (PAHs), in environmental and biological samples. The final toxic effects of these compounds are unknown because the toxic behaviour of each compound is modified when in a complex mixture. This is the first study on the exposure and effect of chemical mixtures on children who live near a petrochemical area. The aim of this study was to evaluate genotoxicity and haematological effects in children environmentally exposed to such mixtures and to determine whether the final effect was modified by the composition of the mixture composition. Biomarkers of exposure to Pb, benzene, toluene, and PAHs were quantified in urine and blood samples of 102 children. DNA damage was evaluated using comet assay, and haematological parameters were determined. Our results show that Pb and toluene did not surpass the exposure guidelines; the exposure was similar in all three localities (Allenede, Mundo Nuevo, and López Mateos). In contrast, exposure to PAHs was observed at three levels of exposure: low, medium, and high. The most severe effects of these mixtures were strictly related to coexposure to high levels of PAHs.

  5. Genotoxic, Cytotoxic, Antigenotoxic, and Anticytotoxic Effects of Sulfonamide Chalcone Using the Ames Test and the Mouse Bone Marrow Micronucleus Test

    PubMed Central

    Borges, Flávio Fernandes Veloso; Bernardes, Aline; Perez, Caridad Noda; Silva, Daniela de Melo e

    2015-01-01

    Chalcones present several biological activities and sulfonamide chalcone derivatives have shown important biological applications, including antitumor activity. In this study, genotoxic, cytotoxic, antigenotoxic, and anticytotoxic activities of the sulfonamide chalcone N-{4-[3-(4-nitrophenyl)prop-2-enoyl]phenyl} benzenesulfonamide (CPN) were assessed using the Salmonella typhimurium reverse mutation test (Ames test) and the mouse bone marrow micronucleus test. The results showed that CPN caused a small increase in the number of histidine revertant colonies in S. typhimurium strains TA98 and TA100, but not statistically significant (p > 0.05). The antimutagenicity test showed that CPN significantly decreased the number of His+ revertants in strain TA98 at all doses tested (p < 0.05), whereas in strain TA100 this occurred only at doses higher than 50 μg/plate (p < 0.05). The results of the micronucleus test indicated that CPN significantly increased the frequency of micronucleated polychromatic erythrocytes (MNPCE) at 24 h and 48 h, revealing a genotoxic effect of this compound. Also, a significant decrease in polychromatic/normochromatic erythrocyte ratio (PCE/NCE) was observed at the higher doses of CPN at 24 h and 48 h (p < 0.05), indicating its cytotoxic action. CPN co-administered with mitomycin C (MMC) significantly decreased the frequency of MNPCE at almost all doses tested at 24 h (p < 0.05), showing its antigenotoxic activity, and also presented a small decrease in MNPCE at 48 h (p > 0.05). Additionally, CPN co-administered with MMC significantly increased PCE/NCE ratio at all doses tested, demonstrating its anticytotoxic effect. In summary, CPN presented genotoxic, cytotoxic, antigenotoxic, and anticytotoxic properties. PMID:26335560

  6. Exposure to runoff from coal-tar-sealed pavement induces genotoxicity and impairment of DNA repair capacity in the RTL-W1 fish liver cell line

    USGS Publications Warehouse

    Kienzler, Aude; Mahler, Barbara J.; Van Metre, Peter C.; Schweigert, Nathalie; Devaux, Alain; Bony, Sylvie

    2015-01-01

    Coal-tar-based (CTB) sealcoat, frequently applied to parking lots and driveways in North America, contains elevated concentrations of polycyclic aromatic hydrocarbons (PAHs) and related compounds. The RTL-W1 fish liver cell line was used to investigate two endpoints (genotoxicity and DNA-repair-capacity impairment) associated with exposure to runoff from asphalt pavement with CTB sealcoat or with an asphalt-based sealcoat hypothesized to contain about 7% CTB sealcoat (AS-blend). Genotoxic potential was assessed by the Formamido pyrimidine glycosylase (Fpg)-modified comet assay for 1:10 and 1:100 dilutions of runoff samples collected from 5 h to 36 d following sealcoat application. DNA-repair capacity was assessed by the base excision repair comet assay for 1:10 dilution of samples collected 26 h and 36 d following application. Both assays were run with and without co-exposure to ultraviolet-A radiation (UVA). With co-exposure to UVA, genotoxic effects were significant for both dilutions of CTB runoff for three of four sample times, and for some samples of AS-blend runoff. Base excision repair was significantly impaired for CTB runoff both with and without UVA exposure, and for AS-blend runoff only in the absence of UVA. This study is the first to investigate the effects of exposure to the complex mixture of chemicals in coal tar on DNA repair capacity. The results indicate that co-exposure to runoff from CT-sealcoated pavement and UVA as much as a month after sealcoat application has the potential to cause genotoxicity and impair DNA repair capacity.

  7. Exposure to runoff from coal-tar-sealed pavement induces genotoxicity and impairment of DNA repair capacity in the RTL-W1 fish liver cell line.

    PubMed

    Kienzler, Aude; Mahler, Barbara J; Van Metre, Peter C; Schweigert, Nathalie; Devaux, Alain; Bony, Sylvie

    2015-07-01

    Coal-tar-based (CTB) sealcoat, frequently applied to parking lots and driveways in North America, contains elevated concentrations of polycyclic aromatic hydrocarbons (PAHs) and related compounds. The RTL-W1 fish liver cell line was used to investigate two endpoints (genotoxicity and DNA-repair-capacity impairment) associated with exposure to runoff from asphalt pavement with CTB sealcoat or with an asphalt-based sealcoat hypothesized to contain about 7% CTB sealcoat (AS-blend). Genotoxic potential was assessed by the Formamido pyrimidine glycosylase (Fpg)-modified comet assay for 1:10 and 1:100 dilutions of runoff samples collected from 5 h to 36 d following sealcoat application. DNA-repair capacity was assessed by the base excision repair comet assay for 1:10 dilution of samples collected 26 h and 36 d following application. Both assays were run with and without co-exposure to ultraviolet-A radiation (UVA). With co-exposure to UVA, genotoxic effects were significant for both dilutions of CTB runoff for three of four sample times, and for some samples of AS-blend runoff. Base excision repair was significantly impaired for CTB runoff both with and without UVA exposure, and for AS-blend runoff only in the absence of UVA. This study is the first to investigate the effects of exposure to the complex mixture of chemicals in coal tar on DNA repair capacity. The results indicate that co-exposure to runoff from CT-sealcoated pavement and UVA as much as a month after sealcoat application has the potential to cause genotoxicity and impair DNA repair capacity.

  8. Evaluation of genotoxic effects of Apitol (cymiazole hydrochloride) in vitro by measurement of sister chromatid exchange.

    PubMed

    Stanimirovic, Zoran; Stevanovic, Jevrosima; Jovanovic, Slobodan; Andjelkovic, Marko

    2005-12-30

    Apitol, with cymiazole hydrochloride as the active ingredient, is used in bee-keeping against the ectoparasitic mite Varroa destructor. The preparation was evaluated for genotoxicity in cultured human peripheral blood lymphocytes. Sister chromatid exchange, the mitotic index and the cell proliferation index were determined for three experimental concentrations of Apitol (0.001, 0.01 and 0.1 mg/ml). All concentrations significantly (p < 0.001) increased the mitotic index (MI = 7.35+/-0.18%, 8.31+/-0.20% and 12.33+/-0.25%, respectively), the proliferative index (PI = 1.83+/-0.01, 1.84+/-0.01 and 1.88+/-0.02, respectively) and the frequency of sister chromatid exchange (SCE = 8.19+/-1.81, 8.78+/-1.80 and 13.46+/-1.88, respectively), suggesting that cymiazole hydrochloride has genotoxic potential. PMID:16309949

  9. Evaluation of genotoxic effects of Apitol (cymiazole hydrochloride) in vitro by measurement of sister chromatid exchange.

    PubMed

    Stanimirovic, Zoran; Stevanovic, Jevrosima; Jovanovic, Slobodan; Andjelkovic, Marko

    2005-12-30

    Apitol, with cymiazole hydrochloride as the active ingredient, is used in bee-keeping against the ectoparasitic mite Varroa destructor. The preparation was evaluated for genotoxicity in cultured human peripheral blood lymphocytes. Sister chromatid exchange, the mitotic index and the cell proliferation index were determined for three experimental concentrations of Apitol (0.001, 0.01 and 0.1 mg/ml). All concentrations significantly (p < 0.001) increased the mitotic index (MI = 7.35+/-0.18%, 8.31+/-0.20% and 12.33+/-0.25%, respectively), the proliferative index (PI = 1.83+/-0.01, 1.84+/-0.01 and 1.88+/-0.02, respectively) and the frequency of sister chromatid exchange (SCE = 8.19+/-1.81, 8.78+/-1.80 and 13.46+/-1.88, respectively), suggesting that cymiazole hydrochloride has genotoxic potential.

  10. Three-Dimensional Transgenic Cell Models to Quantify Space Genotoxic Effects

    NASA Technical Reports Server (NTRS)

    Gonda, S.; Wu, H.; Pingerelli, P.; Glickman, B.

    2000-01-01

    In this paper we describe a three-dimensional, multicellular tissue-equivalent model, produced in NASA-designed, rotating wall bioreactors using mammalian cells engineered for genomic containment of mUltiple copies of defined target genes for genotoxic assessment. The Rat 2(lambda) fibroblasts (Stratagene, Inc.) were genetically engineered to contain high-density target genes for mutagenesis. Stable three-dimensional, multicellular spheroids were formed when human mammary epithelial cells and Rat 2(lambda) fibroblasts were cocultured on Cytodex 3 Beads in a rotating wall bioreactor. The utility of this spheroidal model for genotoxic assessment was indicated by a linear dose response curve and by results of gene sequence analysis of mutant clones from 400micron diameter spheroids following low-dose, high-energy, neon radiation exposure

  11. Effects of triclosan and triclocarban on the growth inhibition, cell viability, genotoxicity and multixenobiotic resistance responses of Tetrahymena thermophila.

    PubMed

    Gao, Li; Yuan, Tao; Cheng, Peng; Bai, Qifeng; Zhou, Chuanqi; Ao, Junjie; Wang, Wenhua; Zhang, Haimou

    2015-11-01

    The information about adverse effects of emerging contaminants on aquatic protozoa is very scarce. The growth inhibition effect, cell viability, genotoxicity and multixenobiotic resistance (MXR) responses of two commonly used antimicrobial agents, triclosan (TCS) and triclocarban (TCC) to protozoan Tetrahymena thermophila were investigated in this study. The results revealed that TCS and TCC can inhibit the growth of T. thermophila with 24h EC50 values of 1063 and 295μgL(-1), respectively. The impairment of plasma membrane was observed after 2h exposure of TCS or TCC at the level of mg/L. Furthermore, it is noticeable that at environmentally relevant concentration (1.0μgL(-1)), both TCS and TCC can lead to statistically significant DNA damage in T. thermophila, while the inhibition of growth and change of cell viability cannot be observed. Our results firstly provide the evidence for genotoxic effects of TCS and TCC on the freshwater protozoan. Additionally, both TCS and TCC were found to inhibit the efflux transporter activities, with the inhibitory potencies of 39% and 40% (using verapamil as a model inhibitor), respectively. Particularly, TCC could significantly down-regulate the expression of MXR related gene Abcb15, which encodes the membrane efflux protein that acting as P-gp in T. thermophila. The results raise the awareness of potential aquatic ecological and human health risks from the exposure of TCS and TCC, as they might potentiate the toxic effects by chemosensitizing with co-existing toxicants.

  12. Genotoxic hazards of azo pigments and other colorants related to 1-phenylazo-2-hydroxynaphthalene.

    PubMed

    Møller, P; Wallin, H

    2000-01-01

    Azo pigments are used extensively as coloring agents in inks, paints and cosmetics. We have surveyed the literature for genotoxic and cancer data on nine colorants, which are structurally related to 1-phenylazo-2-hydroxynaphthalene (C.I. Solvent yellow 14). C.I. Solvent yellow 14 is metabolized by oxidative and peroxidative enzymes. Metabolically activated C.I. Solvent yellow 14 forms both RNA and DNA adducts. It induces liver nodules in rats upon oral administration. Although there is a mixture of negative and positive findings in short-term tests and in animal cancer studies, C.I. Solvent yellow 14 should be considered genotoxic. C.I. Pigment red 3 should be considered carcinogenic but is only weakly genotoxic. C.I. Solvent yellow 7, C.I. Pigment orange 5, C.I. Pigment red 4, and C.I. Pigment red 23 should be considered genotoxic. C.I. Pigment red 53:1 is not genotoxic, and observations of spleen tumors in male rats but not in female rats or mice seem to be related to toxic effects of high doses of C.I. Pigment red 53:1 in this organ. The data in the literature indicate that Pigment red 57:1 is not genotoxic or carcinogenic. We did not find sufficient data for a relevant evaluation of C.I. Pigment red 2 and C.I. Pigment red 64:1. Some of the colorants have in common the 2-amino-1-naphthol structure. This compound is not genotoxic. On the other hand, reductive cleavage of the azo bonds or hydrolysis of anilido bonds would produce aromatic amines, most of which have been under suspicion for genotoxicity or carcinogenicity. For C.I. Pigment red 53:1 and 57:1, sulphonated aromatic amines would be formed that are not genotoxic.

  13. Selective inhibition by aspirin and naproxen of mainstream cigarette smoke-induced genotoxicity and lung tumors in female mice.

    PubMed

    Balansky, Roumen; Ganchev, Gancho; Iltcheva, Marietta; Micale, Rosanna T; La Maestra, Sebastiano; D'Oria, Chiara; Steele, Vernon E; De Flora, Silvio

    2016-05-01

    The role of nonsteroidal anti-inflammatory drugs (NSAIDs) in smoke-related lung carcinogenesis is still controversial. We have developed and validated a murine model for evaluating the tumorigenicity of mainstream cigarette smoke (MCS) and its modulation by chemopreventive agents. In the present study, the protective effects of the nonselective cyclooxygenase inhibitors aspirin and naproxen were investigated by using a total of 277 Swiss H neonatal mice of both genders. Groups of mice were exposed whole-body to MCS during the first 4 months of life, followed by an additional 3.5 months in filtered air in order to allow a better growth of tumors. Aspirin (1600 mg/kg diet) and naproxen (320 mg/kg diet) were given after weanling until the end of the experiment. After 4 months of exposure, MCS significantly enhanced the frequency of micronucleated normochromatic erythrocytes in the peripheral blood of mice, and naproxen prevented such systemic genotoxic damage in female mice. After 7.5 months, exposure of mice to MCS resulted in the formation of lung tumors, both benign and malignant, and in several other histopathological lesions detectable both in the respiratory tract and in the urinary tract. Aspirin and, even more sharply, naproxen significantly inhibited the formation of lung tumors in MCS-exposed mice, but this protective effect selectively occurred in female mice only. These results lend support to the views that estrogens are involved in smoke-related pulmonary carcinogenesis and that NSAIDs have antiestrogenic properties. The two NSAIDs proved to be safe and efficacious in the experimental model used. PMID:26104855

  14. Arsenic Is A Genotoxic Carcinogen

    EPA Science Inventory

    Arsenic is a recognized human carcinogen; however, there is controversy over whether or not it should be considered a genotoxic carcinogen. Many possible modes of action have been proposed on how arsenic induces cancer, including inhibiting DNA repair, altering methylation patter...

  15. Is tetrachloroethylene genotoxic or not?

    PubMed

    Lovell, David

    2010-09-01

    A recent study published in Mutagenesis, in which the ability of tetrachloroethylene to induce DNA damage, detected by the alkaline comet assay, in mouse tissues (liver and kidney) was examined, has resulted in different interpretations of the data for liver as either positive or negative for genotoxicity. Here, I discuss the statistical approaches used and comment on the different conclusions reached.

  16. Evaluation of genotoxicity using automated detection of γH2AX in metabolically competent HepaRG cells.

    PubMed

    Quesnot, Nicolas; Rondel, Karine; Audebert, Marc; Martinais, Sophie; Glaise, Denise; Morel, Fabrice; Loyer, Pascal; Robin, Marie-Anne

    2016-01-01

    The in situ detection of γH2AX was recently reported to be a promising biomarker of genotoxicity. In addition, the human HepaRG hepatoma cells appear to be relevant for investigating hepatic genotoxicity since they express most of drug metabolizing enzymes and a wild type p53. The aim of this study was to determine whether the automated in situ detection of γH2AX positive HepaRG cells could be relevant for evaluation of genotoxicity after single or long-term repeated in vitro exposure compared to micronucleus assay. Metabolically competent HepaRG cells were treated daily with environmental contaminants and genotoxicity was evaluated after 1, 7 and 14 days. Using these cells, we confirmed the genotoxicity of aflatoxin B1 and benzo(a)pyrene and demonstrated that dimethylbenzanthracene, fipronil and endosulfan previously found genotoxic with comet or micronucleus assays also induced γH2AX phosphorylation. Furthermore, we showed that fluoranthene and bisphenol A induced γH2AX while no effect had been previously reported in HepG2 cells. In addition, induction of γH2AX was observed with some compounds only after 7 days, highlighting the importance of studying long-term effects of low doses of contaminants. Together, our data demonstrate that automated γH2AX detection in metabolically competent HepaRG cells is a suitable high-through put genotoxicity screening assay.

  17. Reduction in fluoride-induced genotoxicity in mouse bone marrow cells after substituting high fluoride-containing water with safe drinking water.

    PubMed

    Podder, Santosh; Chattopadhyay, Ansuman; Bhattacharya, Shelley

    2011-10-01

    Treatment of mice with 15 mg l(-1) sodium fluoride (NaF) for 30 days increased the number of cell death, chromosomal aberrations (CAs) and 'cells with chromatid breaks' (aberrant cells) compared with control. The present study was intended to determine whether the fluoride (F)-induced genotoxicity could be reduced by substituting high F-containing water after 30 days with safe drinking water, containing 0.1 mg F ions l(-1). A significant fall in percentage of CAs and aberrant cells after withdrawal of F-treatment following 30 days of safe water treatment in mice was observed which was highest after 90 days, although their levels still remained significantly high compared with the control group. This observation suggests that F-induced genotoxicity could be reduced by substituting high F-containing water with safe drinking water. Further study is warranted with different doses and extended treatment of safe water to determine whether the induced damages could be completely reduced or not.

  18. Effects of prenatal exposure to diesel exhaust particles on postnatal development, behavior, genotoxicity and inflammation in mice

    PubMed Central

    Hougaard, Karin S; Jensen, Keld A; Nordly, Pernille; Taxvig, Camilla; Vogel, Ulla; Saber, Anne T; Wallin, Håkan

    2008-01-01

    Background Results from epidemiological studies indicate that particulate air pollution constitutes a hazard for human health. Recent studies suggest that diesel exhaust possesses endocrine activity and therefore may affect reproductive outcome. This study in mice aimed to investigate whether exposure to diesel exhaust particles (DEP; NIST 2975) would affect gestation, postnatal development, activity, learning and memory, and biomarkers of transplacental toxicity. Pregnant mice (C57BL/6; BomTac) were exposed to 19 mg/m3 DEP (~1·106 particles/cm3; mass median diameter ≅ 240 nm) on gestational days 9–19, for 1 h/day. Results Gestational parameters were similar in control and diesel groups. Shortly after birth, body weights of DEP offspring were slightly lower than in controls. This difference increased during lactation, so by weaning the DEP exposed offspring weighed significantly less than the control progeny. Only slight effects of exposure were observed on cognitive function in female DEP offspring and on biomarkers of exposure to particles or genotoxic substances. Conclusion In utero exposure to DEP decreased weight gain during lactation. Cognitive function and levels of biomarkers of exposure to particles or to genotoxic substances were generally similar in exposed and control offspring. The particle size and chemical composition of the DEP and differences in exposure methods (fresh, whole exhaust versus aged, resuspended DEP) may play a significant role on the biological effects observed in this compared to other studies. PMID:18331653

  19. A FLUORESCENCE-BASED SCREENING ASSAY FOR DNA DAMAGE INDUCED BY GENOTOXIC INDUSTRIAL CHEMICALS

    EPA Science Inventory

    The possibility of deliberate or accidental release of toxic chemicals in industrial, commercial or residential settings has indicated a need for rapid, cost-effective and versatile monitoring methods to prevent exposures to humans and ecosystems. Because many toxic industrial c...

  20. Cytotoxic and genotoxic activities of waters and sediments from highway and parking lot runoffs.

    PubMed

    Haile, Tadele Measho; Mišík, Miroslav; Grummt, Tamara; Halh, Al-Serori; Pichler, Clemens; Knasmueller, Siegfried; Fuerhacker, Maria

    2016-01-01

    The genotoxicity of water and sediment samples from stormwater treatment systems and water from urban highway runoff was tested in the Salmonella/microsome assays with Salmonella typhimurium, micronucleus assay (Trad-MN) with plants and with human-derived liver cells (HepG2), or comet assay with HepG2. Cytotoxicity of water samples was studied using either reactive oxygen species (ROS) generation, cell proliferation or dye exclusion assay in HepG2. Concentrations of several contaminants in the tested samples were also measured. Results suggested that urban highway runoff exposed to severe vehicle traffic emissions caused genotoxic effects in comet assay and in Trad-MN assays. Sediments induced either mutagenic effects in strain YG1024 or genotoxic effects in Trad-MN assay. These effects could be due to the presence of nitro-polycyclic aromatic hydrocarbons (NPAHs) which possess carcinogenic and mutagenic properties. Influent and effluents of stormwater treatment systems did not induce genotoxic activity or effects on HepG2 cell viability; however, the influents were able to induce ROS generation and cell proliferation in HepG2 cells. As the methods require a sterile filtration of the water samples, this could have also removed particulate-associated polycyclic aromatic hydrocarbons (PAHs) and resulted in a less pronounced induction of genotoxicity, as would be expected by PAH contamination.

  1. Cytotoxic and genotoxic activities of waters and sediments from highway and parking lot runoffs.

    PubMed

    Haile, Tadele Measho; Mišík, Miroslav; Grummt, Tamara; Halh, Al-Serori; Pichler, Clemens; Knasmueller, Siegfried; Fuerhacker, Maria

    2016-01-01

    The genotoxicity of water and sediment samples from stormwater treatment systems and water from urban highway runoff was tested in the Salmonella/microsome assays with Salmonella typhimurium, micronucleus assay (Trad-MN) with plants and with human-derived liver cells (HepG2), or comet assay with HepG2. Cytotoxicity of water samples was studied using either reactive oxygen species (ROS) generation, cell proliferation or dye exclusion assay in HepG2. Concentrations of several contaminants in the tested samples were also measured. Results suggested that urban highway runoff exposed to severe vehicle traffic emissions caused genotoxic effects in comet assay and in Trad-MN assays. Sediments induced either mutagenic effects in strain YG1024 or genotoxic effects in Trad-MN assay. These effects could be due to the presence of nitro-polycyclic aromatic hydrocarbons (NPAHs) which possess carcinogenic and mutagenic properties. Influent and effluents of stormwater treatment systems did not induce genotoxic activity or effects on HepG2 cell viability; however, the influents were able to induce ROS generation and cell proliferation in HepG2 cells. As the methods require a sterile filtration of the water samples, this could have also removed particulate-associated polycyclic aromatic hydrocarbons (PAHs) and resulted in a less pronounced induction of genotoxicity, as would be expected by PAH contamination. PMID:27232415

  2. Genotoxic Effects of Low- and High-LET Radiation on Human Epithelial Cells Grown in 2-D Versus 3-D Culture

    NASA Technical Reports Server (NTRS)

    Patel, Z. S.; Cucinotta, F. A.; Huff, J. L.

    2011-01-01

    Risk estimation for radiation-induced cancer relies heavily on human epidemiology data obtained from terrestrial irradiation incidents from sources such as medical and occupational exposures as well as from the atomic bomb survivors. No such data exists for exposures to the types and doses of high-LET radiation that will be encountered during space travel; therefore, risk assessment for space radiation requires the use of data derived from cell culture and animal models. The use of experimental models that most accurately replicate the response of human tissues is critical for precision in risk projections. This work compares the genotoxic effects of radiation on normal human epithelial cells grown in standard 2-D monolayer culture compared to 3-D organotypic co-culture conditions. These 3-D organotypic models mimic the morphological features, differentiation markers, and growth characteristics of fully-differentiated normal human tissue and are reproducible using defined components. Cultures were irradiated with 2 Gy low-LET gamma rays or varying doses of high-LET particle radiation and genotoxic damage was measured using a modified cytokinesis block micronucleus assay. Our results revealed a 2-fold increase in residual damage in 2 Gy gamma irradiated cells grown under organotypic culture conditions compared to monolayer culture. Irradiation with high-LET particle radiation gave similar results, while background levels of damage were comparable under both scenarios. These observations may be related to the phenomenon of "multicellular resistance" where cancer cells grown as 3-D spheroids or in vivo exhibit an increased resistance to killing by chemotherapeutic agents compared to the same cells grown in 2-D culture. A variety of factors are likely involved in mediating this process, including increased cell-cell communication, microenvironment influences, and changes in cell cycle kinetics that may promote survival of damaged cells in 3-D culture that would

  3. In vitro assessment of genotoxic effects of electric arc furnace dust on human lymphocytes using the alkaline comet assay.

    PubMed

    Garaj-Vrhovac, Vera; Orescanin, Visnja; Ruk, Damir; Gajski, Goran

    2009-02-15

    In vitro genotoxic effects of leachates of electric arc furnace dust (EAFD) on human peripheral lymphocytes, assessed prior and following the treatment with a strong alkaline solution were investigated using the alkaline comet assay. Prior and following the treatment, lymphocytes were incubated with leachate of EAFD for 6 and 24 hours at 37 degrees C. Negative controls were also included. Mean values of the tail lengths established in the samples treated with the leachate stemming from the original dust for 6 and 24 hours, were 15.70 microm and 16.78 microm, respectively, as compared to 12.33 microm found in the control sample. Slight, but significant increase in the tail length was also found with the dust treated with a strong alkaline solution (13.37 microm and 13.60 microm). In case of high heavy metal concentrations (the extract of the original furnace dust), the incubation period was revealed to be of significance as well. The obtained results lead to the conclusion that alkaline comet assay could be used as a rapid, sensitive and low-cost tool when assessing genotoxicity of various waste materials, such as leachates of the electric arc furnace dust.

  4. Genotoxic and histopathological biomarkers for assessing the effects of magnetic exfoliated vermiculite and exfoliated vermiculite in Danio rerio.

    PubMed

    Cáceres-Vélez, Paolin Rocio; Fascineli, Maria Luiza; Grisolia, Cesar Koppe; de Oliveira Lima, Emília Celma; Sousa, Marcelo Henrique; de Morais, Paulo César; Bentes de Azevedo, Ricardo

    2016-05-01

    Magnetic exfoliated vermiculite is a synthetic nanocomposite that quickly and efficiently absorbs organic compounds such as oil from water bodies. It was developed primarily to mitigate pollution, but the possible adverse impacts of its application have not yet been evaluated. In this context, the acute toxicity of magnetic exfoliated vermiculite and exfoliated vermiculite was herein assessed by genotoxic and histopathological biomarkers in zebrafish (Danio rerio). DNA fragmentation was statistically significant for all groups exposed to the magnetic exfoliated vermiculite and for fish exposed to the highest concentration (200mg/L) of exfoliated vermiculite, whereas the micronucleus frequency, nuclear abnormalities and histopathological alterations were not statistically significant for the fish exposed to these materials. In the intestinal lumen, epithelial cells and goblet cells, we found the presence of magnetic exfoliated vermiculite and exfoliated vermiculite, but no alterations or presence of the materials-test in the gills or liver were observed. Our findings suggest that the use of magnetic exfoliated vermiculite and exfoliated vermiculite during standard ecotoxicological assays caused DNA damage in D. rerio, whose alterations may be likely to be repaired, indicating that the magnetic nanoparticles have the ability to promote genotoxic damage, such as DNA fragmentation, but not mutagenic effects. PMID:26878635

  5. Protective effects of xanthohumol against the genotoxicity of heterocyclic aromatic amines MeIQx and PhIP in bacteria and in human hepatoma (HepG2) cells.

    PubMed

    Viegas, Olga; Zegura, Bojana; Pezdric, Marko; Novak, Matjaž; Ferreira, Isabel M P L V O; Pinho, Olívia; Filipič, Metka

    2012-03-01

    Previous studies showed that xanthohumol (XN), a hop derived prenylflavonoid, very efficiently protects against genotoxicity and potential carcinogenicity of the food borne carcinogenic heterocyclic aromatic amine (HAA) 2-amino-3-methylimidazo[4,5-f]quinoline (IQ). In this study, we showed that XN was not mutagenic in Salmonella typhimurium TA98 and did not induce genomic instability in human hepatoma HepG2 cells. In the bacteria XN suppressed the formation of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 2-amino-3,8 dimethylimidazo[4,5-f]quinoxaline (MeIQx) induced mutations in a dose dependent manner and in HepG2 cells it completely prevented PhIP and MeIQx induced DNA strand breaks at nanomolar concentrations. With the QRT-PCR gene expression analysis of the main enzymes involved in the biotransformation of HAAs in HepG2 cells we found that XN upregulates the expression of phase I (CYP1A1 and CYP1A2) and phase II (UGT1A1) enzymes. Further gene expression analysis in cells exposed to MeIQx and PhIP in combination with XN revealed that XN mediated up-regulation of UGT1A1 expression may be important mechanism of XN mediated protection against HAAs induced genotoxicity. Our findings confirm the evidence that XN displays strong chemopreventive effects against genotoxicity of HAAs, and provides additional mechanistic information to assess its potential chemopreventive efficiency in humans. PMID:22138251

  6. Investigation of the genotoxicity of substances migrating from polycarbonate replacement baby bottles to identify chemicals of high concern.

    PubMed

    Mertens, Birgit; Simon, Coraline; Van Bossuyt, Melissa; Onghena, Matthias; Vandermarken, Tara; Van Langenhove, Kersten; Demaegdt, Heidi; Van Hoeck, Els; Van Loco, Joris; Vandermeiren, Karin; Covaci, Adrian; Scippo, Marie-Louise; Elskens, Marc; Verschaeve, Luc

    2016-03-01

    Due to the worldwide concern that bisphenol A might act as an endocrine disruptor, alternative materials for polycarbonate (PC) have been introduced on the European market. However, PC-replacement products might also release substances of which the toxicological profile--including their genotoxic effects--has not yet been characterized. Because a thorough characterization of the genotoxic profile of all these substances is impossible in the short term, a strategy was developed in order to prioritize those substances for which additional data are urgently needed. The strategy consisted of a decision tree using hazard information related to genotoxicity. The relevant information was obtained from the database of the European Chemicals Agency (ECHA), in silico prediction tools (ToxTree and Derek Nexus(TM)) and the in vitro Vitotox(®) test for detecting DNA damage. By applying the decision tree, substances could be classified into different groups, each characterized by a different probability to induce genotoxic effects. Although none of the investigated substances could be unequivocally identified as genotoxic, the presence of genotoxic effects could neither be excluded for any of them. Consequently, all substances require more data to investigate the genotoxic potential. However, the type and the urge for these data differs among the substances.

  7. Quizalofop-p-ethyl-induced phytotoxicity and genotoxicity in Lemna minor and Lemna gibba.

    PubMed

    Doganlar, Zeynep B

    2012-01-01

    In this study, the effects of the herbicide, quizalofop-p-ethyl, on pigment contents (total chlorophyll, chlorophyll a/b, carotenoid), antioxidant enzyme [superoxide dismutase (SOD) and guaiacol peroxidase (POD)] activities, lipid peroxidation product (malondialdehyde: MDA) and DNA profiles were investigated in Lemna gibba and Lemna minor. Laboratory-acclimatized plants were treated with quizalofop-p-ethyl at 31.375, 62.75, 125 and 250 mg L(-1) for 24 and 96 h. It was determined that quizalofop-p-ethyl affected both the physiological status and the DNA profiles of L. gibba and L. minor. The photosynthetic pigments of L. gibba were more sensitive to the herbicide than were those of L. minor at both treatment times. SOD and POD activities were elevated in both plants at 24 h. However at 96 h, SOD activity decreased in L. minor and had irregular changes in L. gibba.. Significant increases in the amounts of MDA were observed in L. gib