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Sample records for methotrexate-induced micronuclei production

  1. Inhibition of L-tyrosine-induced micronuclei production by phenylthiourea in human melanoma cells.

    PubMed

    Poma, A; Bianchini, S; Miranda, M

    1999-12-13

    It was previously found that L-tyrosine oxidation product(s) are cytotoxic, genotoxic and increase the sister chromatid exchange (SCE) levels in human melanoma cells. In this work, the micronucleus assay has been performed on human melanotic and amelanotic melanoma cell lines (Carl-1 MEL and AMEL) in the presence of 1.0, 0.5 and 0.1 mM L-tyrosine concentrations to investigate if melanin synthesis intermediate(s) increase micronuclei production. L-Tyrosine oxidation product(s) increased the frequency of micronuclei in melanoma cells; 0.1 mM phenylthiourea (PTU), an inhibitor of L-tyrosine oxidation by tyrosinase, lowered the micronucleus production to the control levels. The culture of melanoma cells with high L-tyrosine in the culture medium resulted in a positive response to an ELISA-based apoptotic test. For comparison the effect of L-tyrosine on micronuclei production in human amelanotic melanoma cells was also investigated; the micronucleus production in the presence of 1 mM L-tyrosine in the culture medium was lower than that found with melanotic melanoma cells of the same cell line. The data suggest that melanin synthesis intermediates arising from L-tyrosine oxidation may cause micronuclei production in Carl-1 human melanoma cells; the addition of PTU in the presence of L-tyrosine decreased the frequency of micronuclei to about the control values thus the inhibition of melanogenesis may have some clinical implication in melanotic melanoma.

  2. Nasal cell micronuclei, cytology and clinical symptoms in stainless steel production workers exposed to chromium.

    PubMed

    Huvinen, Markku; Mäkitie, Antti; Järventaus, Hilkka; Wolff, Henrik; Stjernvall, Tuula; Hovi, Arja; Hirvonen, Ari; Ranta, Riikka; Nurminen, Markku; Norppa, Hannu

    2002-09-01

    The objective of the present study was to determine whether workers in stainless steel production with low exposure to various forms of chromium show an increase in micronucleated nasal cells or an excess of nasal symptoms or disease. Altogether, 48 workers employed in a stainless steel production chain were studied, 29 of them in the steel melting shop with exposure to hexavalent chromium (Cr(6+)), 14 in the sintering and crushing departments of the ferrochromium plant with exposure to trivalent chromium (Cr(3+)) and five in the mine with exposure to chromite ore (Cr(3+)). Thirty-nine workers from the cold rolling mill, with very low exposure to chromium, served as referents. All the subjects were never smokers with a minimum of 14 years employment in the same department. There were no significant differences between the exposure groups and the referents regarding the mean frequency of centromere-negative or centromere-positive micronuclei (studied by pancentromeric fluorescence in situ hybridization), nasal diseases and symptoms or mucociliary clearance of the nasal cavity. No statistically significant differences in the incidence of cell atypia or inflammatory cells were detected between the exposed workers and the reference group, except for an increase in lymphocytes among the chromite ore workers. Anterior rhinoscopy indicated slight inflammatory changes in nasal mucosa and secretion more often in the Cr(6+) and Cr(3+) groups than in the referents, the Cr(6+)-exposed workers showing more livid or oedemic epithelium. In conclusion, the stainless steel production workers, with low exposure to dusts or fumes containing hexavalent or trivalent chromium, did not show clinical changes in the nasal mucosa or an increase in nasal cell micronuclei or symptoms of nasal diseases, except for slight changes in the nasal epithelium and secretion.

  3. Methotrexate-induced panniculitis in a patient with rheumatoid arthritis.

    PubMed

    Al Maashari, Raghda; Hamodat, Mowafak M

    2016-12-01

    Methotrexate-induced accelerated nodulosis (MIAN) is not an uncommon adverse effect associated with the use of the methotrexate in rheumatoid arthritis. Limited case reports describe panniculitis as a pathological finding in this setting. A 31-year-old female with seropositive rheumatoid arthritis on methotrexate therapy presented with a 2-week history of sudden onset of painful infiltrated subcutaneous nodules on both forearms. Based on clinical and histological findings, a diagnosis of methotrexate-induced panniculitis was made. The majority of MIAN case reports that we reviewed showed characteristic pathological findings of classic rheumatoid nodules; few reported panniculitis as a finding. This case illustrates the importance of recognizing this phenomenon as methotrexate-induced panniculitis should be considered in the differential diagnosis of any patient receiving methotrexate presenting with a recent history of accelerated nodulosis. Discontinuation of methotrexate remains controversial.

  4. Sodium alginate inhibits methotrexate-induced gastrointestinal mucositis in rats.

    PubMed

    Yamamoto, Atsuki; Itoh, Tomokazu; Nasu, Reishi; Kajiwara, Eiji; Nishida, Ryuichi

    2013-01-01

    Gastrointestinal mucositis is one of the most prevalent side effects of chemotherapy. Methotrexate is a pro-oxidant compound that depletes dihydrofolate pools and is widely used in the treatment of leukemia and other malignancies. Through its effects on normal tissues with high rates of proliferation, methotrexate treatment leads to gastrointestinal mucositis. In rats, methotrexate-induced gastrointestinal mucositis is histologically characterized by crypt loss, callus fusion and atrophy, capillary dilatation, and infiltration of mixed inflammatory cells. The water-soluble dietary fiber sodium alginate (AL-Na) is derived from seaweed and has demonstrated muco-protective and hemostatic effects on upper gastrointestinal ulcers. In the present study, we evaluated the effects of AL-Na on methotrexate-induced small intestinal mucositis in rats. Animals were subcutaneously administered methotrexate at a dosage of 2.5 mg/kg once daily for 3 d. Rats were treated with single oral doses of AL-Na 30 min before and 6 h after methotrexate administration. On the 4th day, small intestines were removed and weighed. Subsequently, tissues were stained with hematoxylin-eosin and bromodeoxyuridine. AL-Na significantly prevented methotrexate-induced small intestinal mucositis. Moreover, AL-Na prevented decreases in red blood cell numbers, hemoglobin levels, and hematocrit levels. These results suggest the potential of AL-Na as a therapy for methotrexate-induced small intestinal mucositis.

  5. Curcumin and folic acid abrogated methotrexate induced vascular endothelial dysfunction.

    PubMed

    Sankrityayan, Himanshu; Majumdar, Anuradha S

    2016-01-01

    Methotrexate, an antifolate drug widely used in rheumatoid arthritis, psoriasis, and cancer, is known to cause vascular endothelial dysfunction by causing hyperhomocysteinemia, direct injury to endothelium or by increasing the oxidative stress (raising levels of 7,8-dihydrobiopterin). Curcumin is a naturally occurring polyphenol with strong antioxidant and anti-inflammatory action and therapeutic spectra similar to that of methotrexate. This study was performed to evaluate the effects of curcumin on methotrexate induced vascular endothelial dysfunction and also compare its effect with that produced by folic acid (0.072 μg·g(-1)·day(-1), p.o., 2 weeks) per se and in combination. Male Wistar rats were exposed to methotrexate (0.35 mg·kg(-1)·day(-1), i.p.) for 2 weeks to induce endothelial dysfunction. Methotrexate exposure led to shedding of endothelium, decreased vascular reactivity, increased oxidative stress, decreased serum nitrite levels, and increase in aortic collagen deposition. Curcumin (200 mg·kg(-1)·day(-1) and 400 mg·kg(-1)·day(-1), p.o.) for 4 weeks prevented the increase in oxidative stress, decrease in serum nitrite, aortic collagen deposition, and also vascular reactivity. The effects were comparable with those produced by folic acid therapy. The study shows that curcumin, when concomitantly administered with methotrexate, abrogated its vascular side effects by preventing an increase in oxidative stress and abating any reduction in physiological nitric oxide levels.

  6. Induction of micronuclei by palmitic acid and its unique radiolytic product 2-dodecylcyclobutanone

    USDA-ARS?s Scientific Manuscript database

    Palmitic acid (PA), one of the most abundant fatty acids in the human diet, can cause oxidative stress, DNA strand breakage, cellular necrosis and apoptosis in human and rodent cells in vitro. Radiolysis of PA leads to the formation of 2-dodecylcyclobutanone (2-DCB), a unique radiolytic product for...

  7. Cancer cells that survive checkpoint adaptation contain micronuclei that harbor damaged DNA.

    PubMed

    Lewis, Cody W; Golsteyn, Roy M

    2016-11-16

    We have examined the relationship between checkpoint adaptation (mitosis with damaged DNA) and micronuclei. Micronuclei in cancer cells are linked to genomic change, and may induce chromothripsis (chromosome shattering). We measured the cytotoxicity of the cancer drug cisplatin in M059K (glioma fibroblasts, IC50 15 μM). Nearly 100% of M059K cells were positive for histone γH2AX staining after 48 h treatment with a cytotoxic concentration of cisplatin. The proportion of micronucleated cells, as confirmed by microscopy using DAPI and lamin A/C staining, increased from 24% to 48%, and the total micronuclei in surviving cells accumulated over time. Promoting entry into mitosis with a checkpoint inhibitor increased the number of micronuclei in cells whereas blocking checkpoint adaptation with a Cdk inhibitor reduced the number of micronuclei. Interestingly, some micronuclei underwent asynchronous DNA replication, relative to the main nuclei, as measured by deoxy-bromo-uracil (BrdU) staining. These micronuclei stained positive for histone γH2AX, which was linked to DNA replication, suggesting that micronuclei arise from checkpoint adaptation and that micronuclei may continue to damage DNA. By contrast the normal cell line WI-38 did not undergo checkpoint adaptation when treated with cisplatin and did not show changes in micronuclei number. These data reveal that the production of micronuclei by checkpoint adaptation is part of a process that contributes to genomic change.

  8. Methotrexate-induced Hodgkin disease in a patient with systemic lupus erythematosus.

    PubMed

    Sliesoraitis, Sarunas; Khan, Rizwan; Rothman, Jan

    2009-06-01

    Methotrexate sodium use in the management of various immunologic disorders has increased--as have the number of reported adverse effects associated with this therapy. While methotrexate has helped combat various autoimmune and cancerous disorders, the paradoxical risk of causing an often fatal malignancy may still occur as a result of the drug's effect on suppressing immune function. We present a case of methotrexate-induced Hodgkin disease in a 48-year-old man with a history of systemic lupus erythematosus (SLE). Discontinuation of methotrexate facilitated Hodgkin disease reversal. In addition, we review other lymphoproliferative hematologic malignancies caused by methotrexate.

  9. Methotrexate-induced toxicity pharmacogenetics: an umbrella review of systematic reviews and meta-analyses.

    PubMed

    Campbell, Jared M; Bateman, Emma; Stephenson, Matthew D; Bowen, Joanne M; Keefe, Dorothy M; Peters, Micah D J

    2016-07-01

    Methotrexate chemotherapy is associated with various toxicities which can result in the interruption or discontinuation of treatment and a subsequently raised risk of relapse. This umbrella systematic review was conducted to synthesize the results of all existing systematic reviews that investigate the pharmacogenetics of methotrexate-induced toxicity, with the aim of developing a comprehensive reference for personalized medicine. Databases searched were PubMed, Embase, JBI Database of Systematic Reviews and Implementation Reports, DARE, and ProQuest. Papers were critically appraised by two reviewers, and data were extracted using a standardized tool. Three systematic reviews on methotrexate-induced toxicity were included in the review. Meta-analyses were reported across Asian, Caucasian, pediatric and adult patients for the MTHFR C677T and A1298C polymorphisms. Toxicity outcomes included different forms of hematologic, ectodermal and hepatic toxicities. Results varied considerably depending on the patient groups and subgroups investigated in the different systematic reviews, as well as the genetic models utilized. However, significant associations were found between the MTHFR C677T allele and; hepatic toxicity, myelosuppression, oral mucositis, gastrointestinal toxicity, and skin toxicity. Additionally, limited evidence suggests that the MTHFR A1298C polymorphism may be associated with decreased risk of skin toxicity and leukopenia. This umbrella systematic review has synthesized the best available evidence on the pharmacogenetics of methotrexate toxicity. The next step in making personalized medicine for methotrexate therapy a clinical reality is research on the effectiveness and cost-effectiveness of MTHFR genotype testing to enable the close monitoring of at-risk patients for the timely initiation of rescue therapies.

  10. Does intraperitoneal medical ozone preconditioning and treatment ameliorate the methotrexate induced nephrotoxicity in rats?

    PubMed Central

    Aslaner, Arif; Çakır, Tuğrul; Çelik, Betül; Doğan, Uğur; Mayir, Burhan; Akyüz, Cebrail; Polat, Cemal; Baştürk, Ahmet; Soyer, Vural; Koç, Süleyman; Şehirli, Ahmet Özer

    2015-01-01

    Methotrexate is a chemotherapeutic agent used for many cancer treatments. It leads to toxicity with its oxidative injury. The purpose of our study is investigating the medical ozone preconditioning and treatment has any effect on the methotrexate-induced kidneys by activating antioxidant enzymes in rats. Eighteen rats were divided into three equal groups; control, Mtx without and with medical ozone. Nephrotoxicity was performed with a single dose of 20 mg/kg Mtx intraperitoneally at the fifteenth day of experiment on groups 2 and 3. Medical ozone preconditioning was performed at a dose of 25 mcg/ml (5 ml) intraperitoneally everyday in the group 3 and treated with medical ozone for five more days while group 2 was received only 5 ml of saline everyday for twenty days. All rats were sacrificed at the end of third week and the blood and kidney tissue samples were obtained to measure the levels of TNF-α, IL-1β, malondialdehyde, glutathione and myeloperoxidase. Kidney injury score was evaluated histolopatologically. Medical ozone preconditioning and treatment ameliorated the biochemical parameters and kidney injury induced by Mtx. There was significant increase in tissue MDA, MPO activity, TNF-α and IL-1β (P<0.05) and significant decrease in tissue GSH and histopathology (P<0.05) after Mtx administration. The preconditioning and treatment with medical ozone ameliorated the nephrotoxicity induced by Mtx in rats by activating antioxidant enzymes and prevented renal tissue. PMID:26550330

  11. Does intraperitoneal medical ozone preconditioning and treatment ameliorate the methotrexate induced nephrotoxicity in rats?

    PubMed

    Aslaner, Arif; Çakır, Tuğrul; Çelik, Betül; Doğan, Uğur; Mayir, Burhan; Akyüz, Cebrail; Polat, Cemal; Baştürk, Ahmet; Soyer, Vural; Koç, Süleyman; Şehirli, Ahmet Özer

    2015-01-01

    Methotrexate is a chemotherapeutic agent used for many cancer treatments. It leads to toxicity with its oxidative injury. The purpose of our study is investigating the medical ozone preconditioning and treatment has any effect on the methotrexate-induced kidneys by activating antioxidant enzymes in rats. Eighteen rats were divided into three equal groups; control, Mtx without and with medical ozone. Nephrotoxicity was performed with a single dose of 20 mg/kg Mtx intraperitoneally at the fifteenth day of experiment on groups 2 and 3. Medical ozone preconditioning was performed at a dose of 25 mcg/ml (5 ml) intraperitoneally everyday in the group 3 and treated with medical ozone for five more days while group 2 was received only 5 ml of saline everyday for twenty days. All rats were sacrificed at the end of third week and the blood and kidney tissue samples were obtained to measure the levels of TNF-α, IL-1β, malondialdehyde, glutathione and myeloperoxidase. Kidney injury score was evaluated histolopatologically. Medical ozone preconditioning and treatment ameliorated the biochemical parameters and kidney injury induced by Mtx. There was significant increase in tissue MDA, MPO activity, TNF-α and IL-1β (P<0.05) and significant decrease in tissue GSH and histopathology (P<0.05) after Mtx administration. The preconditioning and treatment with medical ozone ameliorated the nephrotoxicity induced by Mtx in rats by activating antioxidant enzymes and prevented renal tissue.

  12. Beneficial effect of erdosteine on methotrexate-induced testicular toxicity in mice.

    PubMed

    Oktar, Süleyman; Gökçe, Ahmet; Aydin, Mehmet; Davarci, Mürsel; Meydan, Sedat; Oztürk, Oktay Hasan; Koç, Ahmet

    2010-08-01

    Methotrexate is used to treat certain types of cancer of the breast, skin, head and neck, or lung. Methotrexate can cause serious or life-threatening side effects on liver, lungs, kidneys, and immune system. Methotrexate chemotherapy causes testicular damage in humans. The aim of this study was to investigate the possible protective role of erdosteine on testicular toxicity of methotrexate in mice. Twenty-six male mice were divided into four groups as follows: group 1, control; group 2, erdosteine-treated; group 3, methotrexate-treated; and group 4, methotrexate + erdosteine treated. On the first day of experiment, a single dose of methotrexate was intraperitoneally administered to groups 3 and 4, although a daily single dose of erdosteine was orally administered to group 2 and 4 for 7 days. At the end of the experiment, the testes of the animals were removed and weighed. The levels of total antioxidant capacity and total oxidative stress, and myeloperoxidase activity in the methotrexate group were higher than the control group (p<0.05). Lipid peroxidation levels were not changed in methotrexate group compared with control group. In conclusion, erdosteine could effectively protect the testes in methotrexate-induced toxicity.

  13. Screening of cytoprotectors against methotrexate-induced cytogenotoxicity from bioactive phytochemicals

    PubMed Central

    Wu, Ying; Yang, Jianbo

    2016-01-01

    As a well known anti-neoplastic drug, the cytogenotoxicity of methotrexate (MTX) has received more attention in recent years. To develop a new cytoprotector to reduce the risk of second cancers caused by methotrexate, an umu test combined with a micronucleus assay was employed to estimate the cytoprotective effects of ten kinds of bioactive phytochemicals and their combinations. The results showed that allicin, proanthocyanidins, polyphenols, eleutherosides and isoflavones had higher antimutagenic activities than other phytochemicals. At the highest dose tested, the MTX genetoxicity was suppressed by 34.03%∼67.12%. Of all the bioactive phytochemical combinations, the combination of grape seed proanthocyanidins and eleutherosides from Siberian ginseng as well as green tea polyphenols and eleutherosides exhibited stronger antimutagenic effects; the inhibition rate of methotrexate-induced genotoxicity separately reached 74.7 ± 6.5% and 71.8 ± 4.7%. Pretreatment of Kunming mice with phytochemical combinations revealed an obvious reduction in micronucleus and sperm abnormality rates following exposure to MTX (p < 0.01). Moreover, significant increases in thymus and spleen indices were observed in cytoprotector candidates in treated groups. The results indicated that bioactive phytochemicals combinations had the potential to be used as new cytoprotectors. PMID:27190706

  14. Protective effect of propolis on methotrexate-induced kidney injury in the rat.

    PubMed

    Ulusoy, Hasan Basri; Öztürk, İsmet; Sönmez, Mehmet Fatih

    2016-06-01

    Objectives Propolis is a potent antioxidant and a free radical scavenger. Pharmacological induction of heat shock proteins (HSPs) has been investigated for restoring normal cellular function following an injury. In this study, effect of propolis on HSP-70 expression in methotrexate-induced nephrotoxicity and direct preventive effect of propolis in this toxicity were investigated. Material and methods A total of 40 male Wistar albino rats were divided into four groups: Group 1 was the untreated control. On the eighth day of the experiment, groups 2 and 3 received single intraperitoneal injections of methotrexate (MTX) at 20 mg/kg. Groups 3 and 4 received 100 mg/kg/day propolis (by oral gavage) for 15 d by the first day of the experimental protocol. Then the rats were decapitated under ketamine esthesia and their kidney tissues were removed. HSP-70 expression, apoptosis, and histopathological damage scores were then compared. Results MTX caused epithelial desquamation into the lumen of the tubules, dilatation, and congestion of the peritubular vessels and renal corpuscles with obscure Bowman's space. The number of apoptotic cells (p = 0.000) and HSP-70 (p = 0.002) expression were increased in group 2. Propolis prevented the rise in number of apoptotic cells (p = 0.017), HSP-70 (p = 0.000) expression, and improved kidney morphology. Conclusions It was found that methotrexate gives rise to serious damage in the kidney and propolis is a potent antioxidant agent in preventing kidney injury.

  15. Micronuclei and pesticide exposure.

    PubMed

    Bolognesi, Claudia; Creus, Amadeu; Ostrosky-Wegman, Patricia; Marcos, Ricard

    2011-01-01

    Micronucleus (MN) is a biomarker widely used in biomonitoring studies carried out to determine the genetic risk associated to pesticide exposure. Many in vitro and in vivo studies, as well as epidemiological approaches, have demonstrated the ability of certain chemical pesticides to produce genetic effects including cancer and other chronic pathologies in humans; thus, biomonitoring studies have been carried out to characterise the genetic risk associated to pesticide exposure. It must be noted that 'pesticide exposure' is a broad term covering complex mixtures of chemicals and many variables that can reduce or potentiate their risk. In addition, there are large differences in pesticides used in the different parts of the world. Although pesticides constitute a wide group of environmental pollutants, the main focus on their risk has been addressed to people using pesticides in their working places, at the chemical industry or in the crop fields. Here, we present a brief review of biomonitoring studies carried out in people occupationally exposed to pesticides and that use MN in lymphocytes or buccal cells as a target to determine the induction of genotoxic damage. Thus, people working in the chemical industry producing pesticides, people spraying pesticides and people dedicated to floriculture or agricultural works in general are the subject of specific sections. MN is a valuable genotoxic end point when clear exposure conditions exist like in pesticide production workers; nevertheless, better study designs are needed to overcome the uncertainty in exposure, genetic susceptibility and statistical power in the studies of sprayers and floriculture or agricultural workers.

  16. Taurine protects against methotrexate-induced toxicity and inhibits leukocyte death

    SciTech Connect

    Cetiner, Mustafa; Sener, Goeksel; Sehirli, A. Ozer; Eksioglu-Demiralp, Emel; Ercan, Feriha; Sirvanci, Serap; Gedik, Nursal; Akpulat, Sertac; Tecimer, Tuelay; Yegen, Berrak C. . E-mail: byegen@marmara.edu.tr

    2005-11-15

    The efficacy of methotrexate (MTX), a widely used cytotoxic chemotherapeutic agent, is often limited by severe side effects and toxic sequelae. Regarding the mechanisms of these side effects, several hypotheses have been put forward, among which oxidative stress is noticeable. The present study was undertaken to determine whether taurine, a potent free radical scavenger, could ameliorate MTX-induced oxidative injury and modulate immune response. Following a single dose of methotrexate (20 mg/kg), either saline or taurine (50 mg/kg) was administered for 5 days. After decapitation of the rats, trunk blood was obtained and the ileum, liver, and kidney were removed to measure malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity, and collagen content, as well as histological examination. Our results showed that MTX administration increased the MDA, MPO activity, and collagen contents and decreased GSH levels in all tissues (P < 0.001), while these alterations were reversed in taurine-treated group (P < 0.05-0.01). Elevated (P < 0.001) TNF-{alpha} level observed following MTX treatment was depressed with taurine (P < 0.01). Oxidative burst of neutrophils stimulated by phorbol myristate acetate was reduced in saline-treated MTX group (P < 0.001), while taurine abolished this effect. Similarly, flow cytometric measurements revealed that leukocyte apoptosis and cell death were increased in MTX-treated animals, while taurine reversed these effects (P < 0.05). Reduced cellularity in bone marrow samples of MTX-treated group (P < 0.01) was reversed back to control levels in taurine-treated rats. Severe degeneration of the intestinal mucosa, liver parenchyma, glomerular, and tubular epithelium observed in saline-treated group was improved by taurine treatment. In conclusion, it appears that taurine protects against methotrexate-induced oxidant organ injury and inhibits leukocyte apoptosis and may be of therapeutic potential in alleviating the

  17. Protective effects of propolis on methotrexate-induced testis injury in rat.

    PubMed

    Sönmez, Mehmet Fatih; Çilenk, Kübra Tuğçe; Karabulut, Derya; Ünalmış, Sunay; Deligönül, Erkan; Öztürk, İsmet; Kaymak, Emin

    2016-04-01

    Propolis is an adhesive substance which is collected and used by honeybees. Propolis is a potent antioxidant and a free radical scavenger. This study was designed to determine whether propolis could protect against dysfunction and oxidative stress induced by methotrexate-induced injury in rat testis. A total of 40 male Wistar albino rats were divided into four groups: group 1 was the untreated control. On the eighth day of the experiment, groups 2 and 3 received single intraperitoneal injections of methotrexate (MTX) at 20mg/kg. Groups 3 and 4 received 100mg/kg/day propolis (by oral gavage) for 15 days by the first day of the experimental protocol. Then the rats were decapitated under anesthesia, and their testes were removed. The histopathological and biochemical analysis along with apoptosis assessment of testis tissues were compared. Immunohistochemical analysis of Heat shock protein-70 (HSP-70) and Proliferating Cell Nuclear Antigen (PCNA) were performed. The phenolic characterization of propolis was performed by Liquid chromatography-mass spectrometry (LC-MS/MS). Methotrexate caused tended to increase in malondialdehyde level and in the number of apoptotic cells; it also caused a decrease in MSTD and JTBS, PCNA and HSP-70 expression and xanthine oxidase levels in group 2. Propolis prevented the rise in malondialdehyde, xanthine oxidase levels and HSP-70 expression and improved testicular morphology and JTBS. It was found that, methorexate gives rise to serious damage in the testes and propolis is a potent antioxidant agent in preventing testicular injury. Copyright © 2016. Published by Elsevier Masson SAS.

  18. Methotrexate induces apoptosis in CaSki and NRK cells and influences the organization of their actin cytoskeleton.

    PubMed

    Mazur, Antonina Joanna; Nowak, Dorota; Mannherz, Hans Georg; Malicka-Błaszkiewicz, Maria

    2009-06-24

    Methotrexate is a widely used drug in treatments of various types of malignancies and in the therapy of rheumatoid arthritis. The goal of our study was to look at the effect of this dihydrofolate reductase inhibitor on the actin cytoskeleton, since actin plays an important role in cancer transformation and metastasis. For this reason we compared results obtained from experiments on CaSki (human uterine cervix cancer) and NRK (normal fibroblastic rat kidney) cells treated with methotrexate. It has been shown previously that methotrexate can induce apoptosis. Therefore we first examined whether methotrexate induces apoptosis in our model cells. For this aim we applied several assays like Caspase Glo 3/7, DNA fragmentation and binding of phosphatidylserine by annexin V-fluorescein. The data obtained indicated that methotrexate induces programmed cell death in CaSki and NRK cells. However, differences between CaSki and NRK cells were observed in the morphological alterations and dynamics of apoptosis induced by methotrexate. It seemed that cancer cells were more sensitive towards the cell death inducing activity at lower concentrations of methotrexate. Analysis by confocal microscopy of methotrexate-treated cells demonstrated that treatment with this folate antagonist affected the actin cytoskeleton, although the dis-organization of the actin cytoskeleton after treatment with methotrexate differed between cancer and normal cells.

  19. The protective effects of Prunus armeniaca L (apricot) against methotrexate-induced oxidative damage and apoptosis in rat kidney.

    PubMed

    Vardi, Nigar; Parlakpinar, Hakan; Ates, Burhan; Cetin, Asli; Otlu, Ali

    2013-09-01

    This study was conducted to evaluate a possible protective role of apricot in apoptotic cell death induced by methotrexate (MTX) and renal damage by different histological and biochemical parameters. Twenty-eight rats were divided into four groups, control, apricot, methotrexate, and apricot + methotrexate. Methotrexate induced renal failure, as shown by significant serum creatinine and urea elevation. Additionally, the results indicated that methotrexate significantly induced lipid peroxidation and reduced antioxidant activities in rats. In contrast, apricot significantly prevented toxic effects of methotrexate via increased catalase, superoxide dismutase, and glutathione levels but decreased formation of malondialdehyde. Also, it was determined that exposure to methotrexate leads to significant histological damage in kidney tissue such as glomerulosclerosis and apoptosis. On the other hand, these effects can be eliminated with apricot diet. These data indicate that apricot may be useful in preventing undesirable effects of MTX such as nephrotoxicity.

  20. Number of centromeric signals in micronuclei and mechanisms of aneuploidy.

    PubMed

    Iarmarcovai, G; Botta, A; Orsière, T

    2006-09-30

    Genome instability or changes in chromosome structure and number are important facets of oncogenesis. Aneuploidy is a major cause of human reproductive failure and plays a large role in cancer. It is therefore important that any increase in its frequency due to occupational exposure to mutagens and carcinogens should be recognized and controlled. In recent years, the cytokinesis-block micronucleus assay has emerged as a biomarker of chromosome/genome damage relevant to cancer. Fluorescent in situ hybridisation using human pancentromeric DNA probes discriminates between the presence of acentric chromosomal fragments and whole chromosomes in binucleated micronucleated lymphocytes. The separated analysis of centromeric micronuclei may improve the sensitivity of the micronucleus assay in detecting genotoxic effects and chromosome instability. Our previous findings suggest that aneugenic events leading to micronuclei (MN) containing a single centromere (C1+MN) and two or more centromeres (Cx+MN) may arise through different pathways. Chromosome migration impairment would lead to increased C1+MN frequency whereas centrosome amplification would induce Cx+MN with three or more centromeric signals. Additional studies that target cellular defects on the centrosome (microtubule nucleation, organization of the spindle poles, cell cycle progression) are required to better understand aneuploid cell production.

  1. Zinc Supplementation Alone Is Effective for Partial Amelioration of Methotrexate-induced Intestinal Damage.

    PubMed

    Musa, Nurul Syarbani Eliana; Howarth, Gordon Stanley; Tran, Cuong Duy

    2015-01-01

    Chemotherapeutic agents such as methotrexate (MTX) are commonly used in the treatment of cancer. MTX is an antimetabolite and antifolate drug that targets folate production in rapidly dividing intestinal cells during deoxyribonucleic acid/ribonucleic acid (DNA/RNA) synthesis, thus indiscriminately diminishing enterocyte numbers and disrupting brush-border enzyme activities. The resultant damage leads to a debilitating condition known as intestinal mucositis. New treatment strategies need to be developed for mucositis, as currently no effective treatment exists. The efficacy of zinc in combination with the probiotic Streptococcus salivarius subsp thermophilus (TH-4) to ameliorate MTX-induced mucositis was investigated. C57BL/6 mice were randomly assigned to 5 groups: (1) negative control group-saline + saline (SS group); (2) MTX-treated control group-saline + MTX (SM group); (3) MTX-treated intervention group-zinc + TH-4 probiotic + MTX (ZPM group); (4) MTX-treated intervention group-zinc + MTX (ZM group); and (5) MTX-treated intervention group-TH-4 probiotic + MTX (PM group). The mice were gavaged daily from days 1-16 with their respective treatments. From days 6-8, a total of 3 consecutive, daily subcutaneous injections of MTX were used to induce mucositis in the 4 MTX-treated intervention groups, with saline used for the negative controls. The study was conducted in the gastroenterology unit at the Women's and Children's Health Network, North Adelaide, SA, Australia. Mice were sacrificed on days 10, 13, and 16. Measurements included body weight, the disease activity index, small-intestine (SI) length and weight, villus height, crypt depth, and mucosal thickness. Also, gut tissues were collected for histological assessments, evaluation of myeloperoxidase (MPO) activity, and analysis of metallothionein (MT) levels. On days 10 and 13, the treatments received by the ZPM and ZM groups resulted in significantly less jejunal damage (P < .05) compared with the MTX

  2. Emergence of micronuclei as a genomic biomarker

    PubMed Central

    Sabharwal, Robin; Verma, Parul; Syed, Mohammed Asif; Sharma, Tamanna; Subudhi, Santosh Kumar; Mohanty, Saumyakanta; Gupta, Shivangi

    2015-01-01

    The presence of micronuclei (MN) in mammalian cells is related to several mutagenetic stresses. MN are formed as a result of chromosome damage and can be readily identified in exfoliated epithelial cells. MN is chromatin particles derived from acentric chromosomal fragments, which are not incorporated into the daughter nucleus after mitosis. It can be visualized by chromatin stains. A variety of factors influences the formation of MN in cells such as age, sex, genetic constitution, physical and chemical agents, adverse habits such as tobacco, areca nut chewing, smoking, and alcohol consumption. Micronucleation has important implications in the genomic plasticity of tumor cells. The present paper reviews the origin, fate and scoring criteria of MN that serves as a biomarker of exposure to genetic toxins, and for the risk of cancer. PMID:26811590

  3. Induction of micronuclei and sister chromatid exchanges by polycyclic and N-heterocyclic aromatic hydrocarbons in cultured human lymphocytes

    SciTech Connect

    Warshawsky, D.; Livingston, G.K.; LaDow, K.

    1995-12-31

    Many natural environments are contaminated with carcinogenic polycyclic aromatic hydrocarbons (PAHs) and N-heterocyclic aromatic hydrocarbons (NHAs) as complex mixtures of coal tar, petroleum, and shale oil. These potentially hazardous substances are prevalent at many former tar production and coal gasification sites. Three polycyclic [benzo(a)pyrene (BaP), benz(a)anthracene (BAA), and 7, 12-dimethylbenz(a)anthracene (DMBA)] and two N-heterocyclic [7H-dibenzo(c,g)carbazole (DBC), and dibenz(a,j)acridine (DBA)] aromatic hydrocarbons were analyzed for cytotoxic and genotoxic effects on human lymphocytes. All of these polyaromatic compounds are normally present in the environment, except for DMBA. Lymphocytes from healthy donors were isolated from whole blood. The 5-ring polycyclic aromatic BaP consistently induced micronuclei in a linear dose-dependent manner with doses from 0.1-10.0 {mu}g/ml, whereas the 4-ring compounds (BAA and DMBA) had no effect on the induction of micronuclei above controls except at 5 and 10 {mu}g/ml. Of the two N-heterocyclic compounds DBC produced a significant increase in micronuclei in lymphocytes, but the dose response tended to plateau above 0.1 {mu}g/ml. DBA showed an effect on the frequency of micronuclei above controls only at high doses of 5 and 10 {mu}g/ml. The average background frequency of micronuclei for 7 lymphocyte donors averaged 3.1 per 1,000 stimulated cells, whereas the average frequency of micronuclei at 10 {mu}g/ml BaP was 36.8 per 1,000 stimulated cells. The lowest effective dose in 2 donors for BaP occurred at 0.1 {mu}g/ml. 61 refs., 2 figs., 6 tabs.

  4. Genotoxic potential evaluation of a cosmetic insoluble substance by the micronuclei assay.

    PubMed

    Dayan, N; Shah, V; Minko, T

    2011-01-01

    An optical brightener (OB) powder (INCI: sodium silicoaluminate (and) glycidoxypropyl trimethyloxysilane/PEI-250 cross fluorescent brightener 230 salt (and) polyvinylalcohol crosspolymer) that is used in cosmetic facial products was tested for its genotoxic potential using the micronuclei test (MNT). It is a solid dry powder with an average size of 5 microns that is insoluble but dispersible in water. This study describes the exposure of cell culture to positive controls with and without enzymatic activation and to the test compound in different concentrations. We evaluated three end points: microscopic observation and quantification of micronuclei formation, and cell viability and proliferation. Both positive controls induced significant changes that were observed under the microscope and quantified. Based on its chemical nature, it was not anticipated that the test substance will degrade under the conditions of the experiments. However, the test is required to make sure that when solublized, impurities that may be present, even at trace levels, will not induce a genotoxic effect. The test compound did not promote micronuclei formation or change the viability or proliferation rate of cells. During this study we faced challenges such as solubilization and correlating viability data to genotoxicity data. These are described in the body of the paper. We believe that with the emergence of the 7(th) European amendment that bans animal testing, sharing these data and the study protocol serves as a key in building the understanding of the utilization of in vitro studies in the safety assessment of cosmetic ingredients.

  5. FISH analysis on spontaneously arising micronuclei in the ICF syndrome.

    PubMed Central

    Stacey, M; Bennett, M S; Hulten, M

    1995-01-01

    The ICF syndrome is a rare disorder where patients show undercondensation of the heterochromatic blocks of chromosomes 1, 9, and 16 along with variable immunodeficiency. The undercondensation of the heterochromatic block appears to be restricted to a portion of PHA stimulated T cells. Patients with this syndrome also show an increase in micronuclei formation. We have used dual colour FISH to investigate the chromosomal content of these micronuclei in PHA stimulated peripheral blood cultures, an EBV transformed B cell line, and also micronuclei observed in vivo from peripheral blood smears. Chromosome 1 appears to be present in a higher proportion of micronuclei compared to chromosomes 9 and 16 in both a PHA stimulated culture and an EBV transformed cell line. An 18 centromeric probe, not associated with the ICF syndrome, showed no signal in any of the micronuclei observed. The implications from these observations are that the heterochromatic instability in the ICF syndrome is manifested not only in T but also in B cells and that it is present in vivo. Images PMID:7562960

  6. [Micronuclei and genetic polymorphisms: from exposure to susceptibility].

    PubMed

    Iarmarcovai, G; Botta, A; Orsière, T

    2007-01-01

    The concept of genetic susceptibility and interactions between genetic and environmental factors of risk is a new trend in molecular epidemiology studies of cancers. Micronuclei are biomarkers of chromosome damage due to genetic instability or exposure to environmental mutagens or carcinogens. The micronucleus assay in combination with fluorescent in situ hybridization discriminates between micronuclei containing acentric chromosome fragments (chromosome breakage) and micronuclei containing whole chromosomes (chromosome loss). A recent approach is to associate the biomarkers of genetic susceptibility, which take into account cancer susceptibility and interindividual differences in the response to a genotoxic exposure, and the micronucleus assay, which serves as a biomarker of interactions between the environment and the genetic material of the cell. Information is being gathered on how DNA damage and more particularly the frequency and centromeric content of micronuclei depend on the polymorphisms of genes implicated in xenobiotic metabolism (activation or detoxication), DNA lesion repair, or folate metabolism. For biomonitoring purposes, numerous confounding factors (age, sex, tobacco consumption) influence the micronucleus biomarker, and thus associating genetic polymorphisms to micronuclei would be useful to better define the prevention and prediction of cancer risk.

  7. Micronuclei assay: A potential biomonitoring protocol in occupational exposure studies.

    PubMed

    Palanikumar, L; Panneerselvam, N

    2011-09-01

    As micronuclei (MN) derive from chromosomal fragments and whole chromosomes lagging behind in anaphase, the MN assay can be used to show both clastogenic and aneugenic effects. This particularly concerns the use of MN as a biomarker ofgenotoxic exposure and effects, where differences in MN frequencies between exposed subjects and referents are expected to be small. The present paper reviews the use of the MN assay in biomonitoring of occupational exposure studies.

  8. Mercury-induced micronuclei in skin fibroblasts of beluga whales

    SciTech Connect

    Gauthier, J.M.; Dubeau, H.; Rassart, E.

    1998-12-01

    Beluga whales (Delphinapterus leucas) inhabiting the St. Lawrence estuary are highly contaminated with environmental pollutants and have a high incidence of cancer. Environmental contaminants may be partly responsible for the high incidence of cancer observed in this population. DNA damage plays an important role in the development of cancer. The micronuclei assay was used to test the genotoxic potential of mercury compounds in skin fibroblasts of an Arctic beluga whale. Both mercuric chloride (Hg) and methylmercury (MeHg) induced a highly significant dose-response increase of micronucleated cells. Statistically significant increases in micronucleated cells were observed for 0.5, 5, and 20 {micro}g/ml Hg and 0.05, 0.5, and 2 {micro}g/ml MeHg when compared to control cultures. Concentrations of 0.5, 5, and 20 {micro}g/ml Hg induced a two-, three- and fourfold increase of micronucleated cells, respectively. Treatment with MeHg was one order of magnitude more potent in inducing micronuclei and in inhibiting cell proliferation than Hg. Although results of this in vitro study do not imply that mercury compounds are involved in the etiology of cancer in St. Lawrence beluga whales, significant increases in micronuclei frequency were found at low concentrations of MeHg that are believed to be comparable to concentrations present in certain whales of this population.

  9. Induction of micronuclei in hemocytes of Mytilus edulis and statistical analysis

    SciTech Connect

    Wrisberg, M.N.; Bilbo, C.M.; Spliid, H. )

    1992-04-01

    A genotoxicity test focusing on micronucleus production in the blood cells (hemocytes) of blue mussel M. edulis has been developed as a possible indicator for marine pollution. A linear dose-response relationship was found when M. edulis was exposed to low concentrations (0, 12.5, and 25 mg/liter) of the alkylating agent ethyl methanesulfonate under laboratory conditions, while higher concentrations (50 and 100 mg/liter) resulted in cytotoxic effects. Furthermore the micronuclei (MN) frequencies in wild mussels from four different field locations have been determined. Mussels collected from two polluted sites showed an elevated MN frequency, indicating the presence of genotoxic pollution. A method to determine the micronuclei background level is suggested and the further implications for applying the method in biomonitoring investigations are discussed. The considered M. edulis exhibits a high biological variation, emphasizing the importance of application of a correct statistical method. A systematic approach to the statistical evaluation of the mussel MN test is outlined. The statistical model includes three different situations: (a) estimation of parameters of a single sample, (b) estimation and comparison of two samples, and (c) estimation of a dose-response relationship. Cases (a) and (b) are especially relevant in biomonitoring investigations while case (c) primarily concerns laboratory experiments.

  10. Conventional armament wastes induce micronuclei in wild brown trout Salmo trutta.

    PubMed

    Ayllón, F; Suciu, R; Gephard, S; Juanes, F; Garcia-Vazquez, E

    2000-10-31

    We analysed micronuclei in brown trout Salmo trutta specimens sampled in the Trubia River, upstream and downstream of the emissions from a Spanish military factory to assess genotoxicity risks derived from military wastes. A significant exponential increase in micronuclei counts was found in fish living downstream of the military wastes with respect to fishes inhabiting upstream areas of the same river. In comparison, we only found a linear increase in micronuclei counts in a control stream where an old military factory had been demolished 6 months before sampling. This difference suggests that active discharge of armament factory wastes can directly induce micronuclei and therefore represents a genotoxic risk for the ecosystem.

  11. Micronuclei and other nuclear lesions as genotoxicity indicators in rainbow trout Oncorhynchus mykiss.

    PubMed

    Ayllón, F; Garcia-Vazquez, E

    2001-07-01

    The induction of micronuclei and other nuclear abnormalities in renal erythrocytes of rainbow trout Oncorhynchus mykiss by six genotoxic compounds is evaluated. Colchicine, mitomycin, cyclophosphamide, acrylamide, methyl-methanesulfonate, and N-ethyl-N-nitrosourea were intraperitoneally injected in trout. Our results show that cyclophosphamide induces the formation of micronuclei and also the other nuclear abnormalities; N-ethyl-N-nitrosourea, acrylamide, and colchicine induce only micronuclei; mitomycin-C induces only other nuclear abnormalities but not micronuclei. Methyl-methanesulfonate does not induce nuclear abnormalities in rainbow trout at the dose assayed in this work. The possible genotoxic origin for the different nuclear abnormalities is discussed. Copyright 2001 Academic Press.

  12. Selenoprotein deficiency enhances radiation-induced micronuclei formation.

    PubMed

    Baliga, Manjeshwar S; Diwadkar-Navsariwala, Veda; Koh, Timothy; Fayad, Raja; Fantuzzi, Giamila; Diamond, Alan M

    2008-11-01

    The availability of selenium and the levels of specific selenoproteins might affect cancer risk by influencing the ability of DNA damaging agents to cause genomic instability and mutations. Transgenic mice that express reduced levels of selenoproteins and previously shown to be more susceptible to pathology associated with cancer development were used to study this possibility. These mice were exposed to X-rays and DNA damage assessed in the erythrocytes, where micronuclei formation was higher compared to the same cells obtained from irradiated wild-type controls. To determine whether the selenoprotein glutathione peroxidase-1 (GPx-1) might be involved in this protection, its levels were reduced by siRNA targeting in LNCaP human prostate cells. UV-induced micronuclei frequency was higher in these cells compared to control-transfected cells. These results indicate a role for selenoproteins in protecting DNA from damage and support human data implicating GPx-1 as a possible target of the chemoprotective effect of selenium.

  13. Possible use of porphycenes as a membrane marker for flow cytometric detection of micronuclei

    SciTech Connect

    Wessels, J.M.; Nuesse, M. )

    1993-01-01

    For flow cytometric analysis of micronuclei induced by ionizing radiation or chemicals, debris plays an important role for the unambiguous detection of micronuclei. Several flow cytometric parameters have been used for a discrimination of micronuclei and debris (Schreiber et al., Cytometry 13:90-102, 1992). The lipophilic character of porphycenes can be used to selectively stain cellular and nuclear membranes. This chemical property of porphycenes requires the use of liposomes as a carrier. Porphycenes show high extinction coefficients at 360 nm and high fluorescence quantum yields between 600 nm and 750 nm. Due to their excellent photophysical properties they can therefore be used as a fluoroscent dye in combination with DNA specific dyes. Porphycenes (i.e. hydroxyethyl-tris(methoxyethyl)porphycene, HEPn) were used to either stain selectively the debris produced by membrane particles or to stain the membranes of nuclei and micronuclei for a better discrimination of debris and micronuclei.

  14. [Induction of micronuclei in peripheral blood and bone marrow reticulocytes of male mice after subchronic exposure to x-rays and bisphenol A].

    PubMed

    Radzikowska, Joanna; Gajowik, Aneta; Dobrzyńska, Małgorzata

    2012-01-01

    Ionizing radiation and xenoestrogens are widely present in the human environment. Bisphenol A (BPA) is used to manufacture polycarbonate plastics, epoxy and polyester resins. BPA is present in a great variety of products including: baby bottles, compact disks, thermal paper, safety helmets, bullet resistant laminate, plastic windows, car parts, adhesives, protective coatings, powder paints, polycarbonate bottles and containers, the sheathing of electrical and electronic parts, dental fillings. Food and beverage cans are protected from rusting and corrosion by the application of epoxy resins as inner coatings. Human activities involving the use of radiation and radioactive materials in industry, agriculture and research cause radiation exposure in addition to natural exposure coming from cosmic rays and naturally occurring radioactive substances. The aim of the study was to estimate the effects of bisphenol A, X-rays and combined exposure to X-rays and bisphenol A on the induction of micronuclei in the peripheral blood and in bone marrow reticulocytes of laboratory mice. Pzh-Sfis male mice were exposed for 8 weeks. Animals were treated with bisphenol A diluted in drinking water (5 mg/kg bw, 10 mg/kg bw, 20 mg/kg bw), irradiated 0.05 Gy of X-rays or exposed to a combination of both (0.05 Gy + 5 mg/kg bw BPA). The samples of peripheral blood were taken at 1, 4 and 8 week following the start of exposure, whereas the bone marrow after the end of experiment, only. The induction of micronuclei in reticulocytes were evaluated by using fluorescence microscope. Bisphenol A as well as ionizing radiation stimulated induction of micronuclei in peripheral blood and bone marrow reticulocytes. After the irradiation the level of micronuclei increased, whereas after exposure to BPA decreased related to time expired from beginning of experiment. Combined exposure of ionizing radiation and bisphenol A induced significantly higher frequency of micronuclei compared to the effect

  15. Micronuclei in genotoxicity assessment: from genetics to epigenetics and beyond

    PubMed Central

    Luzhna, Lidiya; Kathiria, Palak; Kovalchuk, Olga

    2013-01-01

    Micronuclei (MN) are extra-nuclear bodies that contain damaged chromosome fragments and/or whole chromosomes that were not incorporated into the nucleus after cell division. MN can be induced by defects in the cell repair machinery and accumulation of DNA damages and chromosomal aberrations. A variety of genotoxic agents may induce MN formation leading to cell death, genomic instability, or cancer development. In this review, the genetic and epigenetic mechanisms of MN formation after various clastogenic and aneugenic effects on cell division and cell cycle are described. The knowledge accumulated in literature on cytotoxicity of various genotoxins is precisely reflected and individual sensitivity to MN formation due to single gene polymorphisms is discussed. The importance of rapid MN scoring with respect to the cytokinesis-block micronucleus assay is also evaluated. PMID:23874352

  16. Catastrophic nuclear envelope collapse in cancer cell micronuclei

    PubMed Central

    Hatch, Emily M.; Fischer, Andrew H.; Deerinck, Thomas J.; Hetzer, Martin W.

    2013-01-01

    Summary During mitotic exit missegregated chromosomes can recruit their own nuclear envelope (NE) to form micronuclei (MN). MN have reduced functioning compared to primary nuclei in the same cell, although the two compartments appear to be structurally comparable. Here we show that over 60% of MN undergo an irreversible loss of compartmentalization during interphase due to NE collapse. This disruption of the MN, which is induced by defects in nuclear lamina assembly, drastically reduces nuclear functions and can trigger massive DNA damage. MN disruption is associated with chromatin compaction and invasion of endoplasmic reticulum (ER) tubules into the chromatin. We identified disrupted MN in both major subtypes of human non-small cell lung cancer, suggesting that disrupted MN could be a useful objective biomarker for genomic instability in solid tumors. Our study shows that NE collapse is a key event underlying MN dysfunction and establishes a link between aberrant NE organization and aneuploidy. PMID:23827674

  17. Three-dimensional organization of micronuclei induced by colchicine in PtK sub 1 cells

    SciTech Connect

    Geraud, G.; Laquerriere, F.; Masson, C.; Arnoult, J.; Labidi, B.; Hernandez-Verdun, D. )

    1989-03-01

    In PtK{sub 1} cells micronucleated by colchicine, the authors previously demonstrated that some micronuclei contain a single chromosome. Here, they investigated interphase chromosome organization in micronucleated PtK{sub 1} cells using conventional electron microscopy and three-dimensional computer reconstruction. The distribution of micronuclei was not always polarized, but in some cells they formed a ring. When this occurred, centrioles and Golgi apparatus were located inside the ring. On freeze-fracture replicas, they observed that nuclear pore distinction among the micronuclei was heterogeneous, and on thin sections some micronuclei displayed an incomplete nuclear envelope, with gaps in the double membrane and areas without lamina or condensed chromatin. By autoradiography, they showed that the fibrillar dots were not sites of active transcription. They applied three dimensional reconstruction to one micronucleated cell containing 22 micronuclei whose size indicated that each micronucleus probably contained one chromosome. In this cell they demonstrated that only the smallest micronuclei had an incomplete nuclear envelope. The presence in micronuclei of either nucleoli or fibrillar dots was found to be mutually exclusive. Taken together, these findings indicate that in the diploid nuclei of PtK{sub 1} cells, the three-dimensional organization of the nucleolar domain seems to be directly controlled by the X-chromosome.

  18. Meiotic micronuclei induced by X-rays in early spermatids of the rat.

    PubMed

    Lähdetie, J; Parvinen, M

    1981-03-01

    In mutagenicity studies a rapid detection of chromosomal damage in mammalian germ cells would be very valuable. Encouraged by the usefulness of the bone-marrow micronucleus test, we applied analogous method to the assay of micronuclei induced during meiotic reduction divisions in the adult male rat by X-irradiation. The micronuclei were observed in early post-meiotic cells which were enriched using a transillumination phas-contrast microscopic method. The frequency of micronuclei was scored at various dose levels and at various time intervals. The results indicate a linear increase in the frequency of micronuclei 24 h after X-irradiation with doses of 0, 10, 50, 150, 300 and 600 rad. The highest frequency of micronuclei was observed after 900 rad whereas lower frequencies were found after 1200 rad. The lowest dose giving a statistically significant increase above the control level was 50 rad. The stages of meiosis showed different sensitivities to the chromosome-breaking action of X-rays. The maximal incidence of micronuclei was found 18 h after irradiation which was considered to reflect the great radiosensitivity of diakinesis-metaphase I. The anesthetized group of control animals showed a slightly higher frequency of micronuclei than the non-anesthetized controls. Potentials of the new method for mutagen testing are discussed.

  19. The effect of 835.62 MHz FDMA or 847.74 MHz CDMA modulated radiofrequency radiation on the induction of micronuclei in C3H 10T(1/2) cells.

    PubMed

    Bisht, Kheem S; Moros, Eduardo G; Straube, William L; Baty, Jack D; Roti Roti, Joseph L

    2002-05-01

    To determine if radiofrequency (RF) radiation induces the formation of micronuclei, C3H 10T(1/2) cells were exposed to 835.62 MHz frequency division multiple access (FDMA) or 847.74 MHz code division multiple access (CDMA) modulated RF radiation. After the exposure to RF radiation, the micronucleus assay was performed by the cytokinesis block method using cytochalasin B treatment. The micronuclei appearing after mitosis were scored in binucleated cells using acridine orange staining. The frequency of micronuclei was scored both as the percentage of binucleated cells with micronuclei and as the number of micronuclei per 100 binucleated cells. Treatment of cells with cytochalasin B at a concentration of 2 microg/ml for 22 h was found to yield the maximum number of binucleated cells in C3H 10T(1/2) cells. The method used for the micronucleus assay in the present study detected a highly significant dose response for both indices of micronucleus production in the dose range of 0.1-1.2 Gy and it was sensitive enough to detect a significant (P > 0.05) increase in micronuclei after doses of 0.3 Gy in exponentially growing cells and after 0.9 Gy in plateau-phase cells. Exponentially growing cells or plateau-phase cells were exposed to CDMA (3.2 or 4.8 W/kg) or FDMA (3.2 or 5.1 W/kg) RF radiation for 3, 8, 16 or 24 h. In three repeat experiments, no exposure condition was found by analysis of variance to result in a significant increase relative to sham-exposed cells either in the percentage of binucleated cells with micronuclei or in the number of micronuclei per 100 binucleated cells. In this study, data from cells exposed to different RF signals at two SARs were compared to a common sham-exposed sample. We used the Dunnett's test, which is specifically designed for this purpose, and found no significant exposure-related differences for either plateau-phase cells or exponentially growing cells. Thus the results of this study are not consistent with the possibility that

  20. Incidence of chromosomal aberrations and micronuclei in cave tour guides.

    PubMed

    Bilban, M; Bilban-Jakopin, C; Vrhovec, S

    2001-01-01

    An analysis of structural chromosomal aberrations (SCA) and micronucleus tests (MN) were performed in 38 subjects, cave tour guides and in appropriate control group. The dominant type of chromosomal aberrations in tourist guides were chromosomal breaks (0.013 per cell) and acentric fragments (0.011 per cell). In the control group, these aberrations were present up to 0.008 on cells. Considering the analysed cells of the guides in total (33,556), the incidence of dicentric and rings range is below 0.0008 on cells, even though three dicentric and ring chromosoms were found already in the first 1000 in vitro metaphases of some guides. Only 0.0003 dicentrics and neither other translocations were found in control group (ambiental exposure). The incidence of micronuclei in cytokinesis blocked lymphocytes ranged from 12-32 per 500 CB cells in the cave tour guides and from 4-11 per 500 CB cells in control group. Measurements of radon and its daughters were performed at different locations in the cave. Annual doses from 40-60 mSv were estimated per 2000 work hours for cave guides. The changes found in the genome of somatic cells may be related to the exposure doses of radon and its daughters, although smoking should not be ignored.

  1. The relationship between micronuclei in human lymphocytes and selected micronutrients in vegetarians and non-vegetarians.

    PubMed

    Kazimírová, Alena; Barancoková, Magdaléna; Krajcovicová-Kudlácková, Marica; Volkovová, Katarína; Staruchová, Marta; Valachovicová, Martina; Pauková, Viera; Blazícek, Pavel; Wsólová, Ladislava; Dusinská, Mária

    2006-12-10

    A vegetarian diet results in higher intake of vitamins and micronutrients, which - although providing antioxidant defence - may lead to deficiency in other micronutrients involved in DNA metabolism and stability (such as vitamins belonging to the B group). The principal difference among various vegetarian diets is the extent to which animal products are avoided. We have performed a pilot study to determine the relationship between the micronucleus frequency in lymphocytes and diet, and we compared the levels of Vitamins C and E, beta-carotene, B(12), folic acid, homocysteine and total antioxidant capacity in healthy vegetarians and non-vegetarians. The vegetarian group, consisting of 24 volunteers (13 women and 11 men), were matched for age and sex with 24 volunteers (12 women and 12 men) with a traditional dietary habit. Among the vegetarians were 13 lacto-ovo-vegetarians with average duration of vegetarian diet 10.8 years (ranging from 5 to 26 years) and 11 lacto-vegetarians with average duration of vegetarian diet 8.2 years (ranging from 3 to 15 years). Homocysteine, Vitamins C and E and beta-carotene levels in plasma were assayed by HPLC, and serum folate and Vitamin B(12) were determined with Elecsys Immunoassay tests. The total antioxidant capacity of plasma was estimated by measuring the ferric-reducing activity in a spectrophotometric assay. Micronuclei were measured in cytokinesis-blocked lymphocytes. Vegetarians had significantly higher levels of Vitamin C and beta-carotene (but not Vitamin E) in plasma compared with non-vegetarians (P<0.001). There were no significant differences in serum levels of folic acid and Vitamin B(12) between the monitored groups. Levels of folic acid in vegetarians correlated with length of vegetarianism (r=0.62, P=0.001, N=24). Vegetarians had elevated levels of homocysteine compared with non-vegetarians (P=0.007), as did vegetarian women compared with non-vegetarian women (P=0.031). We did not find any differences in total

  2. Age-associated micronuclei, kinetochores and sex chromosome loss in men

    SciTech Connect

    Nath, J.; Hando, J.; Tucker, J.D.

    1995-11-01

    Studies on aneuploidy have shown a significant increase in the loss of chromosomes in both males and females with age and also a significant increase in micronucleus formation in lymphocytes with age. This study attempted (1) to ascertain whether the age-associated increase in Y chromosome loss and micronucleus formation are related. (2) to determine whether there is a correlation between Y chromosome-negative metaphase cells and Y chromosome-positive micronuclei from the same donors, and (3) to determine the relationships among the kinetochore status of micronuclei, Y chromosome-positive micronuclei, and age. Blood samples were obtained from thirty-five healthy males ranging in age from 22 to 79 years, and from the umbilical cords of eighteen newborn males. Two thousand binucleated cells were scored per sample. The kinetochore status of each micronucleus was recorded. Slides were then hybridized with the Y chromosome specific probe pHY10, labeled with biotinylated dUTP, and visualized with fluorescein conjugated avidin. All micronucleated cells were relocated and scored as Y+ or Y- depending on their Y probe status. A total of 303 micronuclei were scored, of which 41 (13.5%) contained the Y chromosome. ANOVA shows a significant increase in the number of Y chromosome-positive micronuclei with age (p<0.001). Of the 41 Y+ micronuclei 36 (87.8%) were kinetochore negative, suggesting a relationship between the absence of kinetochore function and micronucleus formation. Also, 500 metaphase spreads per sample were scored for the Y chromosome, showing an increase in Y-cells with age (p<0.001). A correlation analysis between Y chromosome-positive micronuclei and Y chromosome-negative metaphase cells resulted in a correlation coefficient of 0.71 (p.005).

  3. RNA polymerase activity in PtK1 micronuclei containing individual chromosomes: an in vitro and in situ study

    SciTech Connect

    Labidi, B.; Gregoire, M.; Frackowiak, S.; Hernandez-Verdun, D.; Bouteille, M.

    1987-03-01

    Micronuclei have been induced by colchicine in rat kangaroo (Potorous tridactylis) PtK1 cells. The synthesis of RNA was investigated both in isolated micronuclei by quantifying RNA polymerase activities at different ionic strengths with or without inhibitors, and in micronucleated cells by radioautography after (/sup 3/H)uridine pulse labeling. In vitro transcription shows that isolated micronuclei are able to take up (/sup 3/H)UTP. The rate curves of incorporation are close to those of isolated diploid nuclei, though the level of incorporation was relatively lower (65-70%) than control nuclei. This indicates that micronuclei react to the ionic environment and to inhibitors in the same manner as described for many species of isolated diploid nuclei. The labelling distributions plotted from radioautographs show that micronuclei were able to efficiently incorporate the hot precursor. Furthermore, for short pulses there is no homogeneity in the labelling density among the different micronuclei and there is no correlation between the labelling intensity and the size of micronuclei. After 60-min pulse time, there is an enhanced uptake of (/sup 3/H)uridine and all the micronuclei exhibit considerable labelling, although less than control cells. Thus, the micronuclei exhibit some characteristic RNA transcriptional activity in situ as well as after isolation. This material should be a particular interesting model with which to study the physiological activity and the role of each individual interphasic chromosome.

  4. Micronuclei and fluctuating asymmetry in brown trout (Salmo trutta): complementary methods to biomonitor freshwater ecosystems.

    PubMed

    Sánchez-Galán, S; Linde, A R; Izquierdo, J I; García-Vázquez, E

    1998-02-13

    In this work we measured both micronuclei number in kidney erythrocytes and fluctuating asymmetry in wild brown trout (Salmo trutta), caught in different fluvial ecosystems of Asturias (northern Spain) characterized by different levels of anthropic influence. Brown trout samples from rivers with high anthropic influence possessed significantly higher averages of both micronuclei and fluctuating asymmetry than brown trout samples from less anthropic-influenced rivers. These findings demonstrated the sensitivity of the micronucleus test in kidney erythrocytes to biomonitor freshwater ecosystems. The positive association found between micronuclei average and fluctuating asymmetry at the populational level suggests that fluctuating asymmetry tests could be potential indicators of environmental threat. Variation of fish asymmetry with ageing indicates that fluctuating asymmetry surveys of wild populations should be carried out in trouts of the same age class.

  5. Acentromeric micronuclei are increased in peripheral blood lymphocytes of untreated cancer patients.

    PubMed

    Baciuchka-Palmaro, M; Orsière, T; Duffaud, F; Sari-Minodier, I; Pompili, J; Bellon, L; De Méo, M; Digue, L; Favre, R; Botta, A

    2002-09-26

    Increased micronucleated cell rates, dicentric chromosomes, and other chromosomal damages have been reported in lymphocytes of cancer patients prior to the initiation of chemotherapy, and/or radiotherapy. The cause of these chromosomal damages in these lymphocytes remains unclear. In the present work, we investigated whether these micronuclei mainly reflect structural or numerical chromosomal aberrations by applying the cytokinesis-blocked micronucleus (CBMN) assay in combination with fluorescent in situ hybridization (FISH) of a DNA centromeric probe on blood samples of 10 untreated cancer patients (UCPs), and 10 healthy subjects (HSs). Micronucleated binucleated lymphocyte rate was significantly increased in patients (mean+/-S.D.: 19.0 per thousand +/-14.1 versus 9.2 per thousand +/-4.6 in controls). Trinucleated cytokinesis-blocked cells were not significantly higher in patients than in controls. Acentromeric, centromeric, and multicentromeric micronucleus levels were two-fold higher in patients than in controls, but the difference was significant only with acentromeric micronuclei. The percentage of micronuclei containing one or more centromeres averaged 69.2, and 71.5% in patients, and controls, respectively. The percentage of micronuclei containing several centromeres was 44.7% in patients, and 54.6% in controls. Among centromere-positive micronuclei, the percentage of micronuclei containing several centromeres averaged 59.7% in patients, and 75.4% in controls. These results indicate that genetic instability in peripheral blood lymphocytes of UCPs occurs because of enhanced chromosome breakage. However, a substantial proportion of this genetic instability occurs because of defects in chromosome segregation.

  6. Supraadditive formation of micronuclei in preimplantation mouse embryos in vitro after combined treatment with X-rays and caffeine

    SciTech Connect

    Mueller, W.U.S.; Streffer, C.; Wurm, R.

    1985-01-01

    The influence of caffeine (0.1 or 2 mM), X-rays (0.24 Gy or 0.94 Gy, or of a combination of both on the formation of micronuclei in early stages of preimplantation mouse embryos in vitro was studied. X-rays as well as caffeine induced micronuclei. The dose-effect curve after irradiation was linear for the dose range measured. Caffeine did not induce micronuclei if the concentration was 1 mM or less; between 1 mM and 7 mM, however, there was a linear increase in the number of micronuclei. A considerable enhancement of the number of radiation-induced micronuclei was observed when irradiation of the embryos was followed by a treatment with caffeine. Not only was the sum of the single effects exceeded by the combination effects, but the combination results even lay in the range of supraadditivity of the envelope of additivity.

  7. Buccal Micronuclei Assay as a Tool For Biomonitoring DNA Damage in Oral Lichen Planus

    PubMed Central

    Vidyalakshmi, S.; Nirmal, R. Madhavan; Veeravarmal, V.; Santhadevy, A.; Sumathy

    2016-01-01

    Introduction The malignant transformation rate of Oral Lichen Planus (OLP) is between 0% and 5.8%. Oral lesions of lichen planus clinically presents itself multifocally, simulating the process of field cancerization in high risk malignancies. The Buccal MicroNucleus Cytome Assay (BMN Assay) provides a platform to identify the high risk individuals by evaluating the markers of nuclear damage at an earliest micro invasive phase. Aim To evaluate DNA damage in exfoliated buccal mucosal cells in individuals with oral lichen planus lesions and thereby to delineate the high risk group. Materials and Methods Buccal smears from 22 OLP and 10 control samples were stained in modified Feulgen-Rossenback reaction for micronuclei assay. Cytological evaluation of number of MicroNucleated cells (CMN), Total Number of Micronuclei (TMN) in micronucleated cells was done in both groups. Results Frequency of micronucleated cells (CMN) when compared among the study and control group, a mean value of 4.27 ± 1.80 and 0.90 ± 0.88 were obtained respectively. On comparing the total number of micronuclei in the micronucleated cells (TMN) between the study and control groups, a mean value of 5.38 ± 2.42 and 1.5 ± 0.88 were obtained respectively. Conclusion There was a significant increase in the frequency of micronuclei and the micronucleated cells in the oral lichen planus as compared to normal individuals. PMID:27630941

  8. Design of an Automated-Counting System of Cell Micronuclei in Micrographs

    NASA Astrophysics Data System (ADS)

    Lozano, A. V.; Márquez, J. A.; Buenfil, A. E.; Gonsebatt, M. E.

    2004-09-01

    We developed and tested a system for the automatic analysis of cell images in order to identify and count micronuclei configurations in digital images from a microscope. The presence of micronuclei has been used as an indicator of DNA damage, and a fast automated analysis may be suitable for early cancer detection, for example. We describe in this work the image-processing protocol and system comprising: acquisition, color normalization, contrast enhancement, color-background removing, color segmentation, mathematical-morphology filtering and restoration, morphometry, feature extraction and analysis, and counting. Among the morphological features used for discriminating micronuclei configurations, we tested compactness, area ratios and separation of selected features (ideally, a nucleus and one or more micronuclei). Among the mathematical-morphology techniques, we used for instance a modified watershed segmentation algorithm for separating touching features. We present our results on several images, the evaluation and performance of each step, and the main problems we solved by using several techniques from mathematical morphology and color-image processing.

  9. Induction of micronuclei in germinating onion seed root tip cells irradiated with high energy heavy ions.

    PubMed

    Takatsuji, Toshihiro; Takayanagi, Hiroki; Morishita, Kana; Nojima, Kumie; Furusawa, Yoshiya; Nakazawa, Yuka; Matsuse, Michiko; Akamatsu, Sakura; Hirano, Natsuko; Hirashima, Natsuko; Hotokezaka, Saori; Ijichi, Toyomi; Kakimoto, Chika; Kanemaru, Tomomi; Koshitake, Mayumi; Moriuchi, Akiko; Yamamoto, Kensuke; Yoshikawa, Isao

    2010-01-01

    Effects of high LET charged particles on a perfect in-vivo system are an essential theme for the study of the biological effects of radiation. Germinating onion seeds are independent complete organisms and the radiation induced micronuclei in the root chip cells can be examined quantitatively and theoretically. We irradiated with three types of high energy accelerated heavy ions germinating onion seeds using a synchrotron and observed micronuclei in the root tip cells. Micronuclei induction showed characteristic dose responses of an upward convex bell shape and a steep rise near zero doses for all types of the ions. The bell curve dose responses, however, could be explained by a simple mathematical model. A parameter in the model which indicates micronuclei induction frequency and another parameter which indicates induction frequency of lethal damages (or damages delaying cell divisions) per heavy ion track were both proportional to square of the LET. Because we suspected by-stander effect concerning the dose responses rising steeply near zero doses and tapering off for higher doses, we tested acute irradiation to remove time of information transmittance between cells using a single spill (about 0.3 s) of the synchrotron beam. No difference was detected between normal multiple spill irradiations and single spill.

  10. Exposure to Brominated Trihalomethanes in Water During Pregnancy and Micronuclei Frequency in Maternal and Cord Blood Lymphocytes

    PubMed Central

    Pedersen, Marie; Patelarou, Evridiki; Decordier, Ilse; Vande Loock, Kim; Chatzi, Leda; Espinosa, Ana; Fthenou, Eleni; Nieuwenhuijsen, Mark J.; Gracia-Lavedan, Esther; Stephanou, Euripides G.; Kirsch-Volders, Micheline; Kogevinas, Manolis

    2013-01-01

    Background: Water disinfection by-products have been associated with an increased cancer risk. Micronuclei (MN) frequency in lymphocytes is a marker of genomic damage and can predict adult cancer risk. Objective: We evaluated maternal exposure to drinking water brominated trihalomethanes (BTHM) in relation to MN frequency in maternal and cord blood lymphocytes. Methods: MN frequency was examined in 214 mothers and 223 newborns from the Rhea mother–child cohort in Crete, Greece, in 2007–2008. Residential BTHM water concentrations were estimated during pregnancy using tap water analyses and modeling. Questionnaires on water related habits were used to estimate BTHM exposure from all routes. Associations between BTHM and MN frequency were estimated using negative binomial regression. Results: BTHM concentrations in residential tap water during pregnancy ranged from 0.06 to 7.1 μg/L. MN frequency in maternal binucleated lymphocytes was found to increase with BTHM concentrations in residential water for exposure during the first [rate ratio (RR) for 1 μg/L = 1.05; 95% CI: 1.00, 1.11] and second trimesters (RR for 1 μg/L = 1.03; 95% CI: 1.00, 1.06), and through all routes of BTHM exposure during the first trimester (RR for 1 μg/week = 3.14; 95% CI: 1.16, 8.50). Conclusions: These findings suggest that exposure to BTHM may increase the frequency of MN in maternal binucleated lymphocytes. Citation: Stayner LT, Pedersen M, Patelarou E, Decordier I, Vande Loock K, Chatzi L, Espinosa A, Fthenou E, Nieuwenhuijsen MJ, Gracia-Lavedan E, Stephanou EG, Kirsch-Volders M, Kogevinas M. 2014. Exposure to brominated trihalomethanes in water during pregnancy and micronuclei frequency in maternal and cord blood lymphocytes. Environ Health Perspect 122:100–106; http://dx.doi.org/10.1289/ehp.1206434 PMID:24184846

  11. Evidence that ultrafine titanium dioxide induces micronuclei and apoptosis in Syrian hamster embryo fibroblasts.

    PubMed Central

    Rahman, Qamar; Lohani, Mohtashim; Dopp, Elke; Pemsel, Heidemarie; Jonas, Ludwig; Weiss, Dieter G; Schiffmann, Dietmar

    2002-01-01

    Inhaled ultrafine titanium dioxide (UF-TiO2) particles cause pronounced pulmonary inflammation, in contrast to fine TiO2. Previous studies provide evidence for the production of reactive oxygen species by alveolar macrophages, after overloading with UF-TiO2 particles and cytotoxicity of UF-TiO2 in rat lung alveolar macrophages. UF-TiO2 also causes pulmonary fibrosis and lung tumors in rats. UF-TiO2 particles are photogenotoxic, but in general, information on the genotoxicity of UF-TiO2 is still limited. We studied the potential of UF-TiO2 (particle size less than or equal to 20 nm) and fine TiO2 (particle size > 200 nm) to induce chromosomal changes, which can be monitored by the formation of micronuclei (MN) in Syrian hamster embryo (SHE) cells. We also analyzed UF-TiO2-treated cells for apoptosis induction. The MN assay revealed a significant increase in MN induction (p less than or equal to 0.05) in SHE cells after treatment with UF-TiO2 (1.0 micro g/cm2) for 12 hr (mean, 24.5 MN/1,000 cells), 24 hr (mean, 31.13 MN/1,000 cells), 48 hr (mean, 30.8 MN/1,000 cells), 66 hr (mean, 31.2 MN/1,000 cells), and 72 hr (mean, 31.3 MN/1,000 cells). Bisbenzimide staining of the fixed cells revealed typical apoptotic structures (apoptotic bodies), and the apoptosis-specific "DNA ladder pattern" resulting from internucleosomal cleavage was identified by gel electrophoresis. Furthermore, transmission electron microscopy of the exposed cells revealed the typical chromatin compaction of apoptosis. PMID:12153761

  12. Evolution of bubbles from gas micronuclei formed on the luminal aspect of ovine large blood vessels.

    PubMed

    Arieli, R; Marmur, A

    2013-08-01

    It has been shown that tiny gas nanobubbles form spontaneously on a smooth hydrophobic surface submerged in water. These nanobubbles were shown to be the source of gas micronuclei from which bubbles evolved during decompression of silicon wafers. We suggest that the hydrophobic inner surface of blood vessels may be a site of nanobubble production. Sections from the right and left atria, pulmonary artery and vein, aorta, and superior vena cava of sheep (n=6) were gently stretched on microscope slides and exposed to 1013 kPa for 18 h. Hydrophobicity was checked in the six blood vessels by advancing contact angle with a drop of saline of 71±19°, with a maximum of about 110±7° (mean±SD). Tiny bubbles ~30 μm in diameter rose vertically from the blood vessels and grew on the surface of the saline, where they were photographed. All of the blood vessels produced bubbles over a period of 80 min. The number of bubbles produced from a square cm was: in the aorta, 20.5; left atrium, 27.3; pulmonary artery, 17.9; pulmonary vein, 24.3; right atrium, 29.5; superior vena cava, 36.4. More than half of the bubbles were present for less than 2 min, but some remained on the saline-air interface for as long as 18 min. Nucleation was evident in both the venous (superior vena cava, pulmonary artery, right atrium) and arterial (aorta, pulmonary vein, left atrium) blood vessels. This newly suggested mechanism of nucleation may be the main mechanism underlying bubble formation on decompression. Copyright © 2013 Elsevier B.V. All rights reserved.

  13. Induction of micronuclei on Greek hairdressers occupationally exposed to chemical mixtures.

    PubMed

    Vlastos, Dimitris; Ntinopoulos, Alexandros

    2011-10-01

    Since the early 20th century, hairdressers (HD) have been exposed to a wide range of harmful chemical products. To determine the possible genetic damage to HD, as a result of their occupational exposure to combinations of different chemical factors, we applied the micronucleus assay on their peripheral blood lymphocytes cultures. The micronucleus assay was performed on blood samples from 20 Greek female HD and 20 control women, having no connection with the occupation, from the same area. In the results analysis, parameters included were age, smoking habits, and duration of occupational exposure. The results of our study showed a significant increase in HD micronuclei (MN) frequency, compared to the controls (13.4 ± 1.00 vs. 8.05 ± 0.65). The frequency of large-size MN was significantly higher in the HD and presented potential correlation with the phenomenon of aneuploidy. A statistically significant difference in the frequency of MN between HD and controls who smoked was observed, while this was not the case with the non smoker groups. However, multiple regression analysis showed no significant correlation between smoking habits and MN frequency. The observed increase of the frequency of MN in HD is attributed to the long-term occupational exposure of HD in combination with different chemical factors. Since in the literature there are very few similar studies, further combined studies are suggested on a larger number of HD from different countries, combining biological and molecular techniques, as well as chemical analytical methods of determining and tracing the chemical factors in both the occupational environment and their organisms.

  14. The antigenotoxic activities of cactus (Opuntia ficus-indica) cladodes against the mycotoxin zearalenone in Balb/c mice: prevention of micronuclei, chromosome aberrations and DNA fragmentation.

    PubMed

    Zorgui, Lazhar; Ayed-Boussema, Imen; Ayed, Yosra; Bacha, Hassen; Hassen, Wafa

    2009-03-01

    Zearalenone (ZEN) is a potent estrogenic metabolite. Evidence of its cytotoxicity and genotoxicity has recently emerged from several reports. This study was conducted to evaluate the ability of cactus (Opuntia ficus-indica) cladodes to protect Balb/c mice against ZEN induced genotoxicity. To this end, the effect of a single dose of ZEN (40 mg/kg b.w.) alone and with extract of cactus cladodes (25, 50 and 100 mg/kg b.w.) was monitored by measuring: (i) micronuclei induction in bone marrow cells, (ii) chromosome aberrations mainly breaks and gaps in bone marrow cells also and finally and (iii) DNA fragmentation in liver and kidney. Our results clearly show that ZEN is genotoxic to Balb/c mice. It induces DNA damage as indicated by DNA fragmentation, micronuclei and chromosomal aberrations in bone marrow cells. It is of note that cactus cladodes extract assayed alone at high dose (100 mg/kg b.w.) was found completely safe and did not induce any genotoxic effects. The simultaneous administration of cactus cladodes extract with ZEN resulted in an efficient prevention of micronuclei (the number of PCE MN decreased from 71.3+/-6.1 for animals treated with Zen to 32.6+/-15.5 for animals treated with cactus cladodes), chromosomal aberrations frequency (the % of chromosomal aberrations decreased from 38.3+/-3.0 to 18.6+/-1.1) in bone marrow cells and of DNA fragmentation compared to the group treated with ZEN alone. It could be concluded that cactus cladodes extract was effective in the protection against ZEN genotoxicity. This could be relevant, particularly with the emergent demand for natural products which may neutralize the genotoxic effects of the multiple food contaminants.

  15. Induction of Micronuclei in Human Fibroblasts from the Los Alamos High Energy Neutron Beam

    NASA Technical Reports Server (NTRS)

    Cox, Bradley

    2009-01-01

    The space radiation field includes a broad spectrum of high energy neutrons. Interactions between these neutrons and a spacecraft, or other material, significantly contribute to the dose equivalent for astronauts. The 15 degree beam line in the Weapons Neutron Research beam at Los Alamos Nuclear Science Center generates a neutron spectrum relatively similar to that seen in space. Human foreskin fibroblast (AG1522) samples were irradiated behind 0 to 20 cm of water equivalent shielding. The cells were exposed to either a 0.05 or 0.2 Gy entrance dose. Following irradiation, micronuclei were counted to see how the water shield affects the beam and its damage to cell nuclei. Micronuclei induction was then compared with dose equivalent data provided from a tissue equivalent proportional counter.

  16. Induction of Micronuclei in Human Fibroblasts from the Los Alamos High Energy Neutron Beam

    NASA Technical Reports Server (NTRS)

    Cox, Bradley

    2009-01-01

    The space radiation field includes a broad spectrum of high energy neutrons. Interactions between these neutrons and a spacecraft, or other material, significantly contribute to the dose equivalent for astronauts. The 15 degree beam line in the Weapons Neutron Research beam at Los Alamos Nuclear Science Center generates a neutron spectrum relatively similar to that seen in space. Human foreskin fibroblast (AG1522) samples were irradiated behind 0 to 20 cm of water equivalent shielding. The cells were exposed to either a 0.05 or 0.2 Gy entrance dose. Following irradiation, micronuclei were counted to see how the water shield affects the beam and its damage to cell nuclei. Micronuclei induction was then compared with dose equivalent data provided from a tissue equivalent proportional counter.

  17. Analysis of micronuclei in buccal epithelial cells in patients subjected to panoramic radiography.

    PubMed

    Waingade, Manjushri; Medikeri, Raghavendra S

    2012-01-01

    Ionizing radiation is a well-known carcinogen in humans. Chromosomal aberrations and formation of micronuclei in cell cytoplasm are early biological evidence of carcinogenesis. This study was undertaken to assess the genotoxic effect of panoramic radiography in the buccal epithelial cells. The study included 60 healthy individuals (median age 23.5 years; age range 12-65 years) who underwent panoramic radiographic examination. Exfoliated buccal epithelial cells were obtained immediately before and 10 days after radiation exposure. The cells were stained with Giemsa and evaluated for micronuclei by scoring 1000 cells per sample. The paired 't ' test was used to find out the significance of difference in the number of micronuclei before and after x-ray exposure. The Karl Pearson correlation coefficient was used to find out the correlation between age and micronucleated cell frequencies and number of micronucleus per 1000 cells. The ANOVA test was used to find out if there were significant differences in micronucleated cell frequencies between different age-groups. Student's unpaired 't' test was used to find out the significance of difference in micronucleated cell frequencies and number of micronucleus per 1000 cells between genders. The paired 't' test showed that micronucleated cell frequencies (P = 0.02) and number of micronucleus per 1000 cells (P = 0.047) were significantly higher after radiographic exposure. The mean number of micronucleated cells before and after radiation exposure were 0.48 ± 0.14 and 0.51 ± 0.15, respectively. There was statistically significant increase in the frequency of micronuclei in buccal epithelial cells after exposure to panoramic radiography. The correlation of micronucleus frequency with age and gender was statistically nonsignificant. The results indicate that panoramic radiography may induce genotoxic effects in buccal epithelial cells. Considering this risk, panoramic radiography should be used cautiously.

  18. Image Analysis of Cell Micronuclei Micrographs to Evaluate Their Use as Indicators of Cell Damage

    NASA Astrophysics Data System (ADS)

    Lozano, Antonio; Gonsebatt, María E.; Buenfil, Ana E.; Márquez, Jorge

    2003-09-01

    The early biological changes that can be associated with disease are important indicators or biomarkers for the development of preventive screening strategies. Epidemiological studies have shown that the presence of chromosome damage or instability in human lymphocytes could be considered as an indicator of cancer risk. Chromosome damage can also be estimated using the micronuclei (MN) assay. MN are nuclear bodies originated by chromosome breakage or chromosome segregation during cell division. MN assay can be performed in epithelial tissues in direct contact with xenobiotics and carcinogens, becoming an indicator of cancer risk. Cell MN are thus configurations that appear in the cell cytoplasm as small round bodies near the cell nucleus after cell division. Scoring micronuclei requires a trained individual to detect and count MN in approximately 3000-5000 cells from images in a microscope, becoming a tedious, subjective and error-prone task. We describe computer detection and counting techniques using digital image processing and pattern recognition, allowing automated detection and quantification of the cellular micronuclei configurations, making this technique much more effective for fast and reliable assessing of DNA damage by exposure to radiation and toxic substances. Besides gray-level intensities, the shape and configuration of nuclei and candidates of micronuclei had to be evaluated. Among the Image-Processing techniques chosen, Mathematical Morphology allows to process shapes in order to remove unwanted artifacts or details, filling gaps and holes, and separating touching features or weak connections. This shape-processing enabled to implement the morphological and configurational criteria suggested by the biologists.

  19. Cytogenetic effects of pesticides. II. Induction of micronuclei in mouse bone marrow by the insecticide gardona.

    PubMed

    Amer, S M; Fahmy, M A

    1983-01-01

    The induction of micronuclei in mouse bone marrow by the organophosphorus insecticide gardona (also known as tetrachlorvinphos) was tested. 3 routes of administration were used for the pure insecticide: intraperitoneal, oral and dermal. The different routes of treatment with gardona caused toxicity of marrow indicated as significant increases in the percentage of polychromatic erythrocytes over that of the control. Intraperitoneal and oral treatments induced a statistically significant percentage of micronucleated PE.

  20. ISOLATION AND PARTIAL CHARACTERIZATION OF MACRO- AND MICRONUCLEI FROM PARAMECIUM AURELIA

    PubMed Central

    Cummings, Donald J.

    1972-01-01

    A method was developed for the isolation of macro- and micronuclei from Paramecium aurelia. This method utilized ionic and nonionic detergents to rupture the intact cells, calcium ions and spermidine were employed to protect the nuclei, and the nuclei were purified by centrifugation. Macronuclei consisted of 22% DNA, 10% RNA, and 68% protein. Micronuclei were composed of 9% DNA, 11% RNA, and 80% protein. DNA from both macro- and micronuclei had a density of 1.687 g/cc in CsCl and 1.417 g/cc in Cs2SO4. These values corresponded to G + C content of about 23%. The RNA of macronuclei was examined by gel electrophoresis, and two high molecular weight species were identified having molecular Weights of 1.3 x 106 and 2.8 x 106 daltons. Three syngens were studied, and in each case the conditions for isolation of the nuclei were the same and no differences were observed in the properties of the nuclei. PMID:4552140

  1. Sublethal exposure of heavy metals induces micronuclei in fish, Channa punctata.

    PubMed

    Yadav, Kamlesh K; Trivedi, Sunil P

    2009-12-01

    Present studies were designed to evaluate toxic potential of three common heavy metals, adequately present in agro-industrial effluents, viz. mercury, arsenic and copper using in vivo micronucleus assay in an actinopterygiian fish, Channa punctata (2n=32). Ten days laboratory acclimatized fishes were divided into five groups. Groups I and II served as negative and positive controls, respectively and fishes of group III-V were subjected uninterrupted to sublethal concentrations (10% of 96 h LC50) of heavy metal compounds, HgCl2 (0.081 mg L(-1)), As2O3 (6.936 mg L(-1)) and CuSO(4).5H2O (0.407 mg L(-1)) for 24, 48, 72, 96 and 168 h of exposure periods. Significant increase over and above negative control in the frequency of micronuclei was observed in fishes exposed to metal compounds. The average frequency of micronuclei in fishes exposed to Hg(II), As(III) and Cu(II) observed was 9.79, 12.03 and 8.86, respectively. It reveals that the order of induction of micronuclei frequency and toxicity was As>Hg>Cu. Findings depict genotoxic potential of these metal compounds even in sublethal concentrations.

  2. Induction of micronuclei in human fibroblasts across the Bragg curve of energetic heavy ions.

    PubMed

    Wu, H; Hada, M; Meador, J; Hu, X; Rusek, A; Cucinotta, F A

    2006-10-01

    The space environment consists of a varying field of radiation particles including high-energy ions, with spacecraft shielding material providing the major protection to astronauts from harmful exposure. Unlike low-LEpsilonTau gamma or X rays, the presence of shielding does not always reduce the radiation risks for energetic charged-particle exposure. The dose delivered by the charged particle increases sharply as the particle approaches the end of its range, a position known as the Bragg peak. However, the Bragg curve does not necessarily represent the biological damage along the particle path since biological effects are influenced by the track structures of both primary and secondary particles. Therefore, the "biological Bragg curve" is dependent on the energy and the type of the primary particle and may vary for different biological end points. Here we report measurements of the biological response across the Bragg curve in human fibroblasts exposed to energetic silicon and iron ions in vitro at two different energies, 300 MeV/nucleon and 1 GeV/nucleon. A quantitative biological response curve generated for micronuclei per binucleated cell across the Bragg curve did not reveal an increased yield of micronuclei at the location of the Bragg peak. However, the ratio of mono- to binucleated cells, which indicates inhibition of cell progression, increased at the Bragg peak location. These results confirm the hypothesis that severely damaged cells at the Bragg peak are more likely to go through reproductive death and not be evaluated for micronuclei.

  3. Using carbon nanotubes to induce micronuclei and double strand breaks of the DNA in human cells

    NASA Astrophysics Data System (ADS)

    Cveticanin, Jelena; Joksic, Gordana; Leskovac, Andreja; Petrovic, Sandra; Valenta Sobot, Ana; Neskovic, Olivera

    2010-01-01

    Carbon nanotubes are unique one-dimensional macromolecules with promising applications in biology and medicine. Since their toxicity is still under debate, here we present a study investigating the genotoxic properties of purified single wall carbon nanotubes (SWCNTs), multiwall carbon nanotubes (MWCNTs), and amide functionalized purified SWCNTs on cultured human lymphocytes employing cytokinesis block micronucleus assay and enumeration of γH2AX foci as a measure of double strand breaks (DSBs) of the DNA in normal human fibroblasts. SWCNTs induce micronuclei (MN) formation in lymphocytes and decrease the proliferation potential (CBPI) of cells. In a fibroblast cell line the same dose of SWCNTs induces γH2AX foci 2.7-fold higher than in a control. Amide functionalized purified SWCNTs behave differently: they do not disturb the cell proliferation potential of harvested lymphocytes, but induce micronuclei to a higher extent than SWCNTs. When applied on fibroblasts, amide functionalized SWCNTs also induce γH2AX foci, 3.18-fold higher than the control. The cellular effects of MWCNTs display the broad spectrum of clastogenic properties seen as the highest incidence of induced lymphocyte micronuclei and anaphase bridges among nuclei in binucleated cells. Surprisingly, the incidence of induced γH2AX foci was not as high as was expected by the micronucleus test, which indicates that MWCNTs act as clastogen and aneugen agents simultaneously. Biological endpoints investigated in this study indicate a close relationship between the electrochemical properties of carbon nanotubes and observed genotoxicity.

  4. Evidence for copurification of micronuclei in sucrose density gradient-enriched plasma membranes from cell lines.

    PubMed

    Damaraju, Sambasivarao; Zhang, Nancy; Li, Nan; Tao, Lidan; Damaraju, Vijaya L; Dufour, Jennifer; Santos, Cheryl; Sun, Xue-Jun; Mackey, John; Wishart, David S; Cass, Carol E; Li, Liang

    2010-01-01

    Sucrose density gradient-enriched membrane preparations and membrane fraction enrichment through affinity purification techniques are commonly used in proteomic analysis. However, published proteomic profiles characterized by the above methods show the presence of nuclear proteins in addition to membrane proteins. While shuttling of nuclear proteins across cellular compartments and their transient residency at membrane interfaces could explain some of these observations, the presence of nuclear proteins in proteomic profiles generated with crude and enriched membranes could be the result of nonspecific contamination of nuclear debris during cell fractionation procedures. We hypothesized that micronuclei arising from the genomic instability inherent to cancer cells may copurify with plasma membrane fractions on sucrose gradients. Using sucrose gradient-enriched plasma membranes from breast cancer cell lines derived from the MCF-7 cell line, we provide experimental evidence to indicate that micronuclei are present in fresh preparations of plasma membranes. The origin of these micronuclei was traced to budding of nuclei in intact cells. Furthermore, mass spectrometric analysis confirmed the presence of nuclear proteins as well as membrane and associated signaling proteins in sucrose gradient-enriched preparations.

  5. Origin and evolution of binucleated cells and binucleated cells with micronuclei in cisplatin-treated CHO cultures.

    PubMed

    Rodilla, V

    1993-08-01

    It has recently been described that cisplatin is an agent able to induce binucleated cells (BC) in cultured CHO cells. Both the origin and the significance of those cells within a population are unknown although several hypothesis have been suggested such as blocking of cytokinesis or cell fusion. Using interval photography we have found that at least two mechanisms are involved in the production of BC. These cells can arise in a culture as a result of an incomplete process of cell division, i.e. karyokinesis with incomplete cytokinesis or as a result of the mitotic division of a pre-existent BC. The mitotic division of a BC can give rise to different types of daughter cells. These BC sometimes enter mitosis but fail to divide and as a consequence they remain BC. When the process of division is successful (in the vast majority of cases), the results that have been found are either two mononucleated cells or one mononucleated and one binucleated cell. The possible implications and significance of BC and BC with micronuclei in a given population are discussed.

  6. Relationships among micronuclei, nucleoplasmic bridges and nuclear buds within individual cells in the cytokinesis-block micronucleus assay.

    PubMed

    Cheong, Han S J; Seth, Isheeta; Joiner, Michael C; Tucker, James D

    2013-07-01

    Micronuclei have been used extensively in studies as an easily evaluated indicator of DNA damage but little is known about their association with other types of damage such as nucleoplasmic bridges and nuclear buds. Here, radiation-induced clastogenic events were evaluated via the cytokinesis-block micronucleus assay in two normal human lymphoblastoid cell lines exposed to neutrons or γ-radiation. DNA damage induced by the chemical agents mitomycin C and phleomycin was also evaluated in two normal and two mitochondrial mutant human lymphoblastoid cell lines. In addition to micronuclei, nucleoplasmic bridges and nuclear buds were enumerated by recording the coincident presence of these end points within individual cells, and the associations among these three end points were evaluated for all treatment conditions. The common odds ratios for micronuclei and nucleoplasmic bridges were found to be significantly larger than unity, indicating that the presence of one or more micronuclei in a cell imposes a significant risk of having one or more nucleoplasmic bridges in that same cell, and vice versa. The strength of this association did not change significantly with radiation dose or concentration of the chemical clastogens. Common odds ratios for association between micronuclei and buds, and between bridges and buds were also found to be significantly higher than unity. However, associations between micronuclei and buds could not be calculated for some treatments due to heterogeneity in the odds ratios and hence may depend on chemical clastogen concentration or radiation dose. This study provides evidence of how paired analyses among genetic end points in the cytokinesis-block micronucleus assay can provide information concerning abnormalities of cell division and possibly about structural chromosomal rearrangements induced by clastogens.

  7. Chromosome loss caused by DNA fragmentation induced in main nuclei and micronuclei of human lymphoblastoid cells treated with colcemid.

    PubMed

    Yamamoto, Mika; Wakata, Akihiro; Aoki, Yoshinobu; Miyamae, Yoichi; Kodama, Seiji

    2014-04-01

    Aneuploidy, a change in the number of chromosomes, plays an essential role in tumorigenesis. Our previous study demonstrated that a loss of a whole chromosome is induced in human lymphocytes by colcemid, a well-known aneugen. Here, to clarify the mechanism for colcemid-induced chromosome loss, we investigated the relationship between chromosome loss and DNA fragmentation in human lymphoblastoid cells treated with colcemid (an aneugen) compared with methyl methanesulfonate (MMS; a clastogen). We analyzed the number of fluorescence in situ hybridization (FISH) signals targeted for a whole chromosome 2 in cytokinesis-blocked binucleated TK6 cells and WTK-1 cells treated with colcemid and MMS, and concurrently detected DNA fragmentation by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Results revealed that DNA fragmentation occurred in 60% of all binucleated TK6 cells harboring colcemid-induced chromosome loss (30% of micronuclei and 30% of main nuclei). DNA fragmentation was observed in colcemid-induced micronuclei containing a whole chromosome but not in MMS-induced micronuclei containing chromosome fragments. In contrast, colcemid-induced nondisjunction had no effect on induction of DNA fragmentation, suggesting that DNA fragmentation was triggered by micronuclei containing a whole chromosome but not by micronuclei containing chromosome fragments or nondisjunction. In addition, the frequency of binucleated cells harboring chromosome loss with DNA fragmentation in micronuclei or main nuclei was higher in wild-type p53 TK6 cells than in mutated-p53 WTK-1 cells treated with colcemid. Taken together, these present and previous results suggest that colcemid-induced chromosome loss is caused by DNA fragmentation, which is triggered by a micronucleus with a whole chromosome and controlled by the p53-dependent pathway. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Radiosensitization by the ATR Inhibitor AZD6738 through Generation of Acentric Micronuclei

    PubMed Central

    Dillon, Magnus T.; Barker, Holly E.; Pedersen, Malin; Hafsi, Hind; Bhide, Shreerang A.; Newbold, Kate L.; Nutting, Christopher M.

    2017-01-01

    AZD6738 is an orally active ATR inhibitor (ATRi) currently in phase I clinical trials. We found in vitro growth inhibitory activity of this ATRi in a panel of human cancer cell lines. We demonstrated radiosensitization by AZD6738 to single radiation fractions in multiple cancer cell lines independent of both p53 and BRCA2 status by the clonogenic assay. Radiosensitization by AZD6738 to clinically relevant doses of fractionated radiation was demonstrated in vitro using a 3D tumor spheroid model and, in vivo, AZD6738 radiosensitized by abrogating the radiation-induced G2 cell-cycle checkpoint and inhibiting homologous recombination. Mitosis with damaged DNA resulted in mitotic catastrophe as measured by micronucleus formation by live-cell fluorescent-ubiquitination cell-cycle imaging of cell-cycle progression and nuclear morphology. Induction of micronuclei was significantly more prominent for AZD6738 compared with inhibition of the downstream kinase CHK1 alone at isoeffective doses. Micronuclei were characterized as acentric chromosomal fragments, which displayed characteristics of increased DNA damage and cell-cycle dyssynchrony when compared with the primary nucleus. PMID:28062704

  9. Distribution of Micronuclei in Human Fibroblasts across the Bragg Curve of Light and Heavy Ions

    NASA Technical Reports Server (NTRS)

    Hada, M.; Lacy, S.; Gridley, D. S.; Rusek, A.; Cucinotta, F. A.; Wu, H.

    2007-01-01

    The space environment consists of energetic particles of varying mass and energy, and understanding the :biological Bragg curve" is essential in optimizing shielding effectiveness against space radiation induced biological impacts. The "biological Bragg curve" is dependent on the energy and the type of the primary particle, and may vary for different biological endpoints. Previously, we studied the induction of micronuclei (MN) across the Bragg curve of energetic Fe and Si ions, and observed no increased yield of MN at the location of the Bragg peak. However, the ratio of mono- to bi-nucleated cells, which indicates inhibition of cell progression, was found higher at the Bragg peak location in comparison to the plateau region of the Bragg curve. Here, we report the induction of MN in normal human fibroblast cells across the Bragg curve of incident protons generated at Loma Linda University. Similar to Si and Fe ions, the ratio of mono- to bi-nucleated cells showed a clear spike as the protons reached the Bragg peak. Unlike the two heavy ions, however, the MN yield also increased at the Bragg peak location. These results confirm the hypothesis that severely damaged cells at the Bragg peak of heavy, but not light ions are more likely to go through reproductive death and not be evaluated for micronuclei.

  10. Distribution of Micronuclei in Human Fibroblasts across the Bragg Curve of Light and Heavy Ions

    NASA Technical Reports Server (NTRS)

    Hada, M.; Lacy, S.; Gridley, D. S.; Rusek, A.; Cucinotta, F. A.; Wu, H.

    2007-01-01

    The space environment consists of energetic particles of varying mass and energy, and understanding the :biological Bragg curve" is essential in optimizing shielding effectiveness against space radiation induced biological impacts. The "biological Bragg curve" is dependent on the energy and the type of the primary particle, and may vary for different biological endpoints. Previously, we studied the induction of micronuclei (MN) across the Bragg curve of energetic Fe and Si ions, and observed no increased yield of MN at the location of the Bragg peak. However, the ratio of mono- to bi-nucleated cells, which indicates inhibition of cell progression, was found higher at the Bragg peak location in comparison to the plateau region of the Bragg curve. Here, we report the induction of MN in normal human fibroblast cells across the Bragg curve of incident protons generated at Loma Linda University. Similar to Si and Fe ions, the ratio of mono- to bi-nucleated cells showed a clear spike as the protons reached the Bragg peak. Unlike the two heavy ions, however, the MN yield also increased at the Bragg peak location. These results confirm the hypothesis that severely damaged cells at the Bragg peak of heavy, but not light ions are more likely to go through reproductive death and not be evaluated for micronuclei.

  11. Micronuclei Assessment of The Radioprotective Effects of Melatonin and Vitamin C in Human Lymphocytes

    PubMed Central

    Rostami, Aram; Moosavi, Seyed Akbar; Dianat Moghadam, Hassan; Bolookat, Eftekhar Rajab

    2016-01-01

    Objective Critical macromolecules such as DNA maybe damaged by free radicals that are generated from the interaction of ionizing radiation with biological systems. Melatonin and vitamin C have been shown to be direct free radical scavengers. The aim of this study was to investigate the in vivo/in vitro radioprotective effects of melatonin and vitamin C separately and combined against genotoxicity induced by 6 MV x-ray irradiation in human cultured blood lymphocytes. Materials and Methods In this experimental study, fifteen volunteers were divided into three groups of melatonin, vitamin C and melatonin plus vitamin C treatment. Peripheral blood samples were collected from each group before, and 1, 2 and 3 hours after melatonin and vitamin C administration (separately and combined). The blood samples were then irradiated with 200 cGy of 6 MV x-ray. In order to characterize chromosomal aberrations, the lymphocyte samples were cultured with mitogenic stimulus on cytokinesisblocked binucleated cells. Results The samples collected 1hour after melatonin and vitamin C (separately and combined) ingestion exhibited a significant decrease in the incidence of micronuclei compared with their control group (P<0.05). The maximum synergic protection and reduction in frequency of micronuclei (57%) was observed 1 hour after vitamin C and melatonin administration combined. Conclusion We conclude that simultaneous administration of melatonin and vitamin C as radioprotector substances before irradiation may reduce genotoxicity caused by x-ray irradiation. PMID:27054118

  12. Differential micronuclei induction in human lymphocyte cultures by imidacloprid in the presence of potassium nitrate.

    PubMed

    Stivaktakis, Polychronis; Vlastos, Dimitris; Giannakopoulos, Evangelos; Matthopoulos, Demetrious P

    2010-01-08

    Humans are exposed to pesticides as a consequence of their application in farming or their persistence in a variety of media, including food, water, air, soil, plants, animals, and smoke. The interaction of pesticides with environmental factors may result in the alteration of their physicochemical properties. Square wave cathodic stripping voltammetry (SW-CSV), a technique that simulates electrodynamically the cellular membrane, is used to investigate whether the presence of potassium nitrate (KNO(3)) in the culture medium interferes with the genotoxic behavior of imidacloprid. The cytokinesis block micronuclei (CBMN) method is used to evaluate imidacloprid's genotoxicity in the absence or presence of KNO(3) in the culture medium and, as a consequence, its adsorption by lymphocytes. Comparing micronuclei (MN) frequencies in control and imidacloprid-treated blood cell cultures, statistically significant differences were not detected. KNO(3) did not induce MN frequencies compared to control. Statistically significant differences in MN frequencies were observed when blood cell cultures were treated with imidacloprid in the presence of increasing concentrations of KNO(3). SW-CSV revealed that by increasing KNO(3) molarity, imidacloprid's concentration in the culture medium decreased in parallel. This finding indicates that imidacloprid is adsorbed by cellular membranes. The present study suggests a novel role of a harmless environmental factor, such as KNO(3), on the genotoxic behavior of a pesticide, such as imidacloprid. KNO(3) rendered imidacloprid permeable to lymphocytes, resulting in elevated MN frequencies.

  13. [Preliminary study of the frequency of micronuclei in buccal mucosa cells sampled from patients with laryngeal tumors].

    PubMed

    Belowska, Jadwiga; Fraczek, Agnieszka; Rał, Małgorzata; Schmager, Jan; Składzien, Jacek; Strek, Paweł; Scióg, Anna; Trybała, Dorota

    2004-01-01

    The examination of frequency of micronuclei was carried out on two groups of patients with tumors of upper respiratory tract: cancer of larynx (36 individuals) and polyps of larynx (13 persons). Groups of habitants from Katowice, Czestochowa and Nowy Sacz (cities with the different level of air pollution) and separately group of smokers, were considered as the control. It was observed that high frequency of micronuclei in cell of buccal mucosa from individuals exposed on mutagenic substances from the air and cigarette smoke could be a marker of higher risk of carcinogenesis.

  14. [Tripartite motif-containing protein 34 (TRIM34) colocalized with micronuclei chromosome and hampers its movement to equatorial plate during the metaphase stage of mitosis].

    PubMed

    Sun, Dakang; An, Xinye; Ji, Bing; Cheng, Yanli; Gao, Honglian; Tian, Mingming

    2016-06-01

    Objective To examine whether tripartite motif-containing protein 34 (TRIM34) is colocalized with micronuclei and investigate the influence on the movement of micronuclei chromosome in mitosis. Methods The eukaryotic expression vector TRIM34-pEGFP-N3 was constructed, identified and then transfected into HEK293T cells. With 4', 6-diamidino-2-phenylindole 2HCI (DAPI) staining, the colocalization between TRIM34 and micronuclei was observed under a fluorescence microscope. Moreover, MitoTracker(R)Deep Red was used to identify the colocalization between the complex of TRIM34-micronulei and mitochondria under a confocal microscope. Finally, the effect of TRIM34 on the movement of micronuclei chromosome in mitosis was examined. Results DNA sequencing confirmed that the vector TRIM34-pEGFP-N3 was constructed successfully. A fluorescence microscope revealed that TRIM34 could be colocalized with micronuclei in HEK293T cells transfected with TRIM34-pEGFP-N3. In the same manner, a confocal microscope distinctly showed that TRIM34 was colocalized with micronuclei similarly in appearance. However, there was no distinguished colocalization relationship between the complex of TRIM34-micronulei and mitochondria. Interestingly, the micronuclei chromosome conjugated with TRIM34 was hardly transferred to equatorial plate during the metaphase stage of mitosis. Conclusion TRIM34 is colocalized with micronuclei chromosome and hampers its movement to equatorial plate in mitosis.

  15. DIBENZO[A,L]PYRENE INDUCTION OF ERYTHROCYTE MICRONUCLEI IN A/J AND P53-DEFICIENT MICE

    EPA Science Inventory

    DIBENZO[a,l]PYRENE INDUCTION OF ERYTHROCYTE MICRONUCLEI IN AlJ AND P53-DEFICIENT MICE

    Male A/J and C57Bl/6 background p53+/+, p53+/- and p53-/- mice were treated with dibenzo[a,l]pyrene (DB[a,l]P), and micronucleus (MN) frequencies were measured in erythrocytes from bone ...

  16. Adaptive response of blood lymphocytes of inhabitants residing in high background radiation areas of ramsar- micronuclei, apoptosis and comet assays.

    PubMed

    Mohammadi, Shahla; Taghavi-Dehaghani, Mahnaz; Gharaati, Mohammad R; Masoomi, Reza; Ghiassi-Nejad, Mehdi

    2006-11-01

    The hot springs in certain areas of Ramsar contain (226)Ra and (222)Rn. The effects of natural radiation on the inhabitants of these areas and the inhabitant's radiosensitivity or adaptive responses were studied. One group of volunteers from areas with high natural background radiation and another group from areas with normal background radiation were chosen as the case and control group respectively. The frequency of micronuclei, apoptosis, and DNA damage in peripheral blood mononuclear cells were measured following gamma irradiation (4 Gy). The incidence of micronuclei in the case group was significantly lower than that in the control group while their frequency of apoptosis was higher (P < 0.05). However, the rates of induced DNA damage and repair were significantly higher in the case group (P < 0.05). Smaller number of micronuclei and higher levels of apoptosis in the case group could be the result of higher resistance to radiation stress and a more rigorous checkpoint at cell division. However, regarding the alkaline labile sites, the individuals in the case group are more sensitive and susceptible to DNA damage. The results of micronuclei, apoptosis and repair studies suggest that an adaptive response might be induced in people residing in areas with high background radiation.

  17. Coumarin inhibits micronuclei formation induced by benzo(a)pyrene in male but not female ICR mice

    SciTech Connect

    Morris, D.L.; Ward, J.B. Jr. )

    1992-01-01

    Coumarin has been shown to be an effective inhibitor of carcinogenesis in rodents if given before and during the carcinogen treatment. The authors investigated the possibility that pretreatment with coumarin would inhibit the genotoxicity of benzo(a)pyrene (BP) in ICR mice as indicated by the bone marrow micronucleus test, a widely used in vivo test for genotoxicity. The studies showed that pretreatment of male mice with doses of coumarin at 65 or 130 mg/kg/day for 1 week (with 1 day of no treatment at midweek) partially inhibited the genotoxicity of BP at a single intraperitoneal dose of 150 mg/kg. Time course experiments showed a decrease in induced micronuclei in the bone marrow at several time points after the BP treatment, thus indicating a true inhibition and not a lag in the induction of micronuclei. However, no inhibition in micronuclei formation was seen in female mice pretreated with the same doses of coumarin. Coumarin treatment alone did not induce micronuclei in either sex. Future studies are needed to analyze the mechanisms responsible for the difference noted between the sexes.

  18. DIBENZO[A,L]PYRENE INDUCTION OF ERYTHROCYTE MICRONUCLEI IN A/J AND P53-DEFICIENT MICE

    EPA Science Inventory

    DIBENZO[a,l]PYRENE INDUCTION OF ERYTHROCYTE MICRONUCLEI IN AlJ AND P53-DEFICIENT MICE

    Male A/J and C57Bl/6 background p53+/+, p53+/- and p53-/- mice were treated with dibenzo[a,l]pyrene (DB[a,l]P), and micronucleus (MN) frequencies were measured in erythrocytes from bone ...

  19. Baseline micronuclei and nuclear abnormalities frequencies in native fishes from the Paraná River (Argentina).

    PubMed

    Furnus, G N A; Caffetti, J D; García, E M; Benítez, M F; Pastori, M C; Fenocchio, A S

    2014-02-01

    This work aims to establish baseline frequencies of micronuclei (MN) and nuclear abnormalities (NA) in native fish species collected in situ from the Paraná River. For this purpose, the micronucleus test was applied in peripheral blood erythrocytes from specimens obtained from samplings collected at two localities (Posadas and Candelaria, Misiones, Argentina) during the period 2007-2010. The results were statistically analyzed using the Kruskal Wallis test. Data from nine fish species were obtained, among which Steindachnerina brevipinna (Characiformes) revealed the highest baseline frequency of MN and NA, showing statistically significant differences with regard to the other analyzed species. These results are the first report of baseline MN and NA frequencies for native fish species studied and could be useful for future comparisons with data of fishes belonging to other environments.

  20. Marked reduction of radiation-induced micronuclei in human blood lymphocytes pretreated with melatonin

    SciTech Connect

    Vijayalaxmi; Reiter, R.J.; Leal, B.Z.

    1995-07-01

    Human peripheral blood lymphocytes which were pretreated in vitro with melatonin, and endogenously synthesized pineal hormone, for 20 min at 37 {plus_minus} 1{degrees}C exhibited a significant and concentration-dependent reduction in the frequency of {gamma}radiation-induced micronuclei compared with irradiated cells which did not receive the pretreatment. The extent of the reduction observed with 2.0 mM melatonin was similar to that found in lymphocytes pretreated for 20 min with 1.0 M dimethylsulfoxide, a known free radical scavenger. These observations indicate that melatonin may have an active role in protection of humans against genetic damage due to endogenously produced free radicals, and also may be of use in reducing damage due to exposure to physical and chemical mutagens and carcinogens which generate free radicals. 25 refs., 2 tabs.

  1. Flow cytometric detection of micronuclei by combined staining of DNA and membranes

    SciTech Connect

    Wessels, J.M.; Nuesse, M.

    1995-03-01

    A new staining method is presented for flow cytometric measurement of micronuclei (MN) in cell cultures and human lymphocytes using membrane-specific fluorescent dyes in addition to DNA staining. Several combinations of fluorescent membrane and DNA dyes were studied for a better discrimination of MN from debris in a suspension of nuclei and micronuclei. For staining of membranes, the lipophilic dyes 2-hydroxyethyl-7,12,17-tris(methoxyethyl)porphycene (HEPn) and 1,6-diphenyl-1,3,5-hexatriene (DPH) were used in combination with ethidium bromide (EB), proflavine (PF), and Hoechst 33258 (HO). Due to their spectral properties, HO or EB combined with HEPn were not as suitable for the discrimination of MN from debris as was HEPn in combination with PF. With HEPn in combination with PF, however, additional noise was found at low fluorescence intensities, probably due to free fluorescent dye molecules in the solution. The optimal simultaneous staining of membranes and DNA was obtained using a combination of DPH and EB. The induction of MN in Chinese hamster and mouse NIH-3T3 cells by UV-B illumination was studied with this new staining technique. UV-B illumination (280-360 nm) induced MN in both cell lines. Chinese hamster cells were found to be more sensitive to these wavelengths. Illumination with wavelengths above 360 nm did not induce MN in either cell line. The results obtained from human lymphocytes using the combination of EB or DPH were comparable to the results obtained with the combination of EB and HO. 23 refs., 7 figs.

  2. Biomonitoring of primary aluminium industry workers: detection of micronuclei and repairable DNA lesions by alkaline SCGE.

    PubMed

    Crebelli, Riccardo; Carta, Plinio; Andreoli, Cristina; Aru, Gabriella; Dobrowolny, Gabriella; Rossi, Sabrina; Zijno, Andrea

    2002-04-26

    The genetic effects of occupational exposure to low polycyclic aromatic hydrocarbon (PAH) concentrations were investigated in primary aluminium industry workers. The study subjects were employed in a plant that uses pre-baked anode cells, and has relatively low PAH contamination. Forty-two male workers belonging to different job categories (anode fabrication, baking, rodding, electrolysis, maintenance), together with 16 male local residents with no occupational exposure to PAHs were selected for the analysis of micronuclei and DNA lesions in peripheral lymphocytes. The incidence of micronuclei determined in 1000 cytokinesis-blocked cells in each subject was not significantly different between workers and controls (8.5+/-5.4 per thousand versus 9.7+/-4.9 per thousand, respectively), nor between smokers and non-smokers (8.3+/-5.8 per thousand versus 9.2+/-5.1 per thousand), but was significantly (P<0.05) related to the subjects' age. Also the analysis of DNA damage in unstimulated and mitogen-stimulated lymphocytes by single cell gel electrophoresis (SCGE) did not show significant differences between the studied groups (average tail moment values were 0.53+/-0.53 and 0.49+/-0.45 microm in exposed subjects and controls, respectively). However, when lymphocytes were cultured in the presence of cytosine arabinoside (Ara-C, 1 microg/ml for 16h) the SCGE analysis revealed a significant (P=0.018) difference in tail moment values between aluminium workers and controls (1.73+/-1.05 microm versus 0.93+/-0.88 microm, respectively). This difference may highlight an excess of relatively stable DNA lesions, that do not affect strand integrity, and are expressed as intermediates of excision repair in stimulated cells, when gap refilling is inhibited by cytosine arabinoside (Ara-C).

  3. Anticlastogenic effect of Spirulina maxima extract on the micronuclei induced by maleic hydrazide in Tradescantia.

    PubMed

    Ruiz Flores, L Elvia; Madrigal-Bujaidar, Eduardo; Salazar, María; Chamorro, Germán

    2003-02-07

    The aim of this investigation was to determine if extracts of Spirulina maxima reduce the genotoxic damage induced by maleic hydrazide (MH) using the Tradescantia biosssay. Two types of extracts from the alga were prepared: an aqueous extract with two different concentrations, 100 and 500 mg/ml, and a second one, the extract of a 1% solution of dimethyl sulfoxide (DMSO) which corresponded to 100 mg/ml of the alga. The capacity of MH to induce micronuclei (MN) was initially established by administering 0.005, 0.01, and 0.015 mg/ml of the chemical to the Tradescantia inflorescences, and observing its effect after 24 h.The results of this experiment showed a significant MN increase with the two high concentrations tested, although no dose-response effect was observed. For the anticlastogenic assay, the extracts of Spirulina were applied to the inflorescences alone or immediately before the application of MH (0.01 mg/ml) and the induced MN were observed 24 h later. We found that none of the extracts increased the MN level with respect to the untreated plants; also, that MH more or less doubled the basal micronuclei frequency, and finally, that all tested extracts reduced the genotoxic damage caused by MH. The inhibitory indices obtained for the aqueous extracts (100 and 500 mg/ml) and for the DMSO extract were respectively 59, 85, and 56.3%. These data indicate that Spirulina is an anticlastogenic agent and suggest that it is advisable to extend studies on this matter using other biological models.

  4. Micronuclei induction in human lymphocytes induced by carbon ions exposion along the penetrate depth of ions in water

    NASA Astrophysics Data System (ADS)

    Wang, Z. Z.; Li, W. J.; Zhi, D. J.; Qu, Y.; Jing, X. G.

    2009-08-01

    Here we used cytokinesis-block micronucleus assay to measure the biological response along the penetrate depth of ions in water in human lymphocytes exposed to 100 MeV/u incident carbon ions in vitro. Polyethylene shielding was used to change the penetration depth of ions in water. A quantitative biological response curve was generated for micronuclei induction. The results showed a marked increase with the penetrate depth of ions in water in the micronuclei formation, which was consistent with a linear-energy-transfer dependent increase in biological effectiveness. The dose-response relationship for MN information was different at different penetrate depth of ions in water, at the 6 and 11.2 mm penetrate depth of ions in water, the dose-response relationships for the micronucleus frequencies induced by carbon ions irradiation were linear; while it was power function at 17.1 mm penetrate depth.

  5. Brachypodium distachyon – A Useful Model in the Qualification of Mutagen-Induced Micronuclei Using Multicolor FISH

    PubMed Central

    Kus, Arita; Kwasniewska, Jolanta; Hasterok, Robert

    2017-01-01

    Brachypodium distachyon (Brachypodium) is now intensively utilized as a model grass species in various biological studies. Its favorable cytological features create a unique foundation for a convenient system in mutagenesis, thereby potentially enabling the ‘hot spots’ and ‘cold spots’ of DNA damage in its genome to be analyzed. The aim of this study was to analyze the involvement of 5S rDNA, 25S rDNA, the Arabidopsis-type (TTTAGGG)n telomeric sequence and the Brachypodium-originated centromeric BAC clone CB33J12 in the micronuclei formation in Brachypodium root tip cells that were subjected to the chemical clastogenic agent maleic hydrazide (MH). To the best of our knowledge, this is the first use of a multicolor fluorescence in situ hybridization (mFISH) with four different DNA probes being used simultaneously to study plant mutagenesis. A quantitative analysis allowed ten types of micronuclei, which were characterized by the presence or absence of specific FISH signal(s), to be distinguished, thus enabling some specific rules governing the composition of the MH-induced micronuclei with the majority of them originating from the terminal regions of chromosomes, to be identified. The application of rDNA sequences as probes showed that 5S rDNA-bearing chromosomes are involved in micronuclei formation more frequently than the 25S rDNA-bearing chromosomes. These findings demonstrate the promising potential of Brachypodium to be a useful model organism to analyze the effects of various genotoxic agents on the plant nuclear genome stability, especially when the complex FISH-based and chromosome-specific approaches such as chromosome barcoding and chromosome painting will be applied in future studies. PMID:28118403

  6. Effects of orally administered antioxidants on micronuclei and sister chromatid exchange frequency in workers professionally exposed to antineoplastic agents.

    PubMed

    Mrđanović, Jasminka; Jungić, Saša; Šolajić, Slavica; Bogdanović, Višnja; Jurišić, Vladimir

    2012-08-01

    The widespread use of antineoplastic drugs in cancer treatment increased concern about possible hazard to workers involved in the preparation and administration of these drugs. In the present study, the effects of commercial antioxidative drug Oligogal Se on genome protection were analyzed in 15 nurses handling the antineoplastic drugs at the Oncology Department in comparison to twenty healthy volunteers. The nurses took antioxidant mixture Oligogal Se, consisting of vitamins C, E, A and selenium, one capsule per day, over a period of 6 months. Genome damage was measured in peripheral blood lymphocytes by usage of sister chromatid exchange test and the cytokinesis-block micronuclei test. The frequency of sister chromatid exchange (SCE) and micronuclei (MN) in the exposed group was significantly higher when compared to the control group (SCE, p<0.05; MN, p<0.01 respectively). After antioxidant supplementation, the frequency of sister chromatid exchange and micronuclei decreased (p<0.05) when compared with the values from the beginning of the study, but were still above the values of the control group. The effects of confounding factors such as cigarette smoking and cytostatics exposure time were also evaluated. The data indicated that Oligogal Se contributed to the decreasing of genome damages in workers handling the cytostatics. Copyright © 2012 Elsevier Ltd. All rights reserved.

  7. Micronuclei in nasal mucosa, oral mucosa and lymphocytes in students exposed to formaldehyde vapor in anatomy class.

    PubMed

    Ying, C J; Yan, W S; Zhao, M Y; Ye, X L; Xie, H; Yin, S Y; Zhu, X S

    1997-12-01

    The frequency of micronuclei (MN) in cells of the nasal mucosa, oral mucosa and in lymphocytes was evaluated for 25 students in anatomy classes exposed to formaldehyde (FA) over an 8-week period. Each student served as his or her own control. The time-weighted average concentration (TWA) of formaldehyde in anatomical laboratories and in students' dormitories was 0.508 +/- 0.299 mg/m3 and 0.012 +/- 0.0025 mg/m3, respectively. A higher frequency of micronuclei was observed in nasal and oral exfoliative cells after formaldehyde exposure (3.85 +/- 1.48 vs 1.20 +/- 0.676 and 0.857 +/- 0.558 vs 0.568 +/- 0.317, paired-t test: P < 0.001 and P < 0.01, respectively). No significant increase in the frequency of lymphocyte micronuclei was found after formaldehyde exposure (P > 0.05). The present study shows that nasal mucosa cells exposed through respiration are the chief target of FA-induced genotoxic effects.

  8. Spontaneous and mitomycin-C-induced micronuclei in human lymphocytes exposed to extremely low frequency pulsed magnetic fields

    SciTech Connect

    Scarfi, M.R.; Bersani, F.; Cossarizza, A.; Monti, D.; Castellani, G.; Cadossi, R.; Franceschetti, G.; Franceschi, C. )

    1991-04-15

    The cytokinesis block micronucleus method, a very sensitive cytogenetic assay, was used to ascertain the possible genotoxic effects of extremely low frequency pulsed magnetic fields in phytohemagglutinin-stimulated human lymphocytes cultures from 16 healthy donors. Four conditions were studied: lymphocytes not exposed to the field (control cultures); lymphocytes exposed to the field; lymphocytes treated with mitomycin-C and not exposed to the field; and lymphocytes treated with mitomycin-C and exposed to the field. Mitomycin-C-treated cultures were used as control for the micronucleus method, because it is known that mitomycin-C is a potent genotoxic agent, capable of inducing micronuclei. The frequency of micronuclei in field-exposed cultures was similar to the spontaneous frequency observed in control unexposed-cultures. Moreover, the exposure to pulsed magnetic fields did not affect the frequency of micronuclei induced by mitomycin-C, suggesting that, in the experimental conditions used, this kind of field neither affected the integrity of chromosomes nor interfered with the genotoxic activity of mitomycin-C.

  9. Frequencies of micronuclei in bank voles from zones of high radiation at Chernobyl, Ukraine

    SciTech Connect

    Rodgers, B.E.; Baker, R.J.

    2000-06-01

    A population of Clethrionomys glareolus (bank vole) from a highly radioactive area within the Chernobyl, Ukraine exclusion zone was sampled in June 1997 and in June and October 1998. Internal radiation doses from radiocesium were estimated to be as high as 8 rads/d. Total dose, which takes into account the internal dose form radiostrontium and the surrounding environment, was estimated to be 15 to 20 rads/d. In contrast, individuals from a reference population lying outside of the exclusion zone registered negligible levels of contamination. The authors used the micronucleus test in a double-blind study to analyze blood samples from 58 individuals. They scored more than 600,000 polychromatic erythrocytes (PCEs) but could not reject the null hypothesis that the frequency of micronucleated PCEs in voles exposed to radiation was equal to the frequency in unexposed voles. Results of their study stand in sharp contrast to earlier reports of increased frequencies of micronuclei in rodents exposed to fallout of the Chernobyl accident, but with radiation doses that were orders of magnitude lower than those reported here. Radio resistance and experimental methods are possible explanations for these differences in the results.

  10. Potential Uses, Limitations, and Basic Procedures of Micronuclei and Nuclear Abnormalities in Buccal Cells

    PubMed Central

    Torres-Bugarín, Olivia; Zavala-Cerna, María Guadalupe; Nava, Arnulfo; Flores-García, Aurelio; Ramos-Ibarra, María Luisa

    2014-01-01

    The use of biomarkers as tools to evaluate genotoxicity is increasing recently. Methods that have been used previously to evaluate genomic instability are frequently expensive, complicated, and invasive. The micronuclei (MN) and nuclear abnormalities (NA) technique in buccal cells offers a great opportunity to evaluate in a clear and precise way the appearance of genetic damage whether it is present as a consequence of occupational or environmental risk. This technique is reliable, fast, relatively simple, cheap, and minimally invasive and causes no pain. So, it is well accepted by patients; it can also be used to assess the genotoxic effect derived from drug use or as a result of having a chronic disease. Furthermore the beneficial effects derived from changes in life style or taking additional supplements can also be evaluated. In the present paper, we aim to focus on the explanation of MN test and its usefulness as a biomarker; we further give details about procedures to perform and interpret the results of the test and review some factors that could have an influence on the results of the technique. PMID:24778463

  11. Induction of Micronuclei in Human Fibroblasts across the Bragg Curve of Energetic Si and Fe Ions

    NASA Technical Reports Server (NTRS)

    Wu, H.; Rusek, A.; Hada, M.

    2006-01-01

    The space environment consists of a varying field of radiation particles including high-energy ions, with spacecraft shielding material providing the major protection to astronauts from harmful exposure. Unlike low-LET gamma or X-rays, the presence of shielding does not always reduce the radiation risks for energetic charged particle exposure. Since the dose delivered by the charged particle increases sharply as the particle approaches the end of its range, a position known as the Bragg peak, the Bragg curve does not necessarily represent the biological damage along the particle traversal since biological effects are influenced by the track structure of both primary and secondary particles. Therefore, the biological Bragg curve is dependent on the energy and the type of the primary particle, and may vary for different biological endpoints. We studied micronuclei (MN) induction across the Bragg curve of Si and Fe ions at incident energies of 300 MeV/nucleon and 1 GeV/nucleon. A quantitative biological response curve did not reveal an increased yield of MN at the location of the Bragg peak. However, the ratio of mono- to bi-nucleated cells, which indicates inhibition in cell progression, increased at the Bragg peak location. These results confirm the hypothesis that severely damaged cells at the Bragg peak are likely to go through reproduction death.

  12. Micronuclei formation in liver fibrosis samples from patients infected by hepatitis C virus

    PubMed Central

    2010-01-01

    Genetic research on fibrosis outset and its progression in chronic hepatitis (CH) by hepatitis C virus (HCV) are limited. The lack of cytogenetic data led us to investigate the presence of micronuclei (MNi), as a sign of genomic damage. Hepatocytes of hepatic parenchyma from 62 cases diagnosed with CH associated with HCV and displaying different degrees of fibrosis (F1-F4) were analyzed. These data were compared to 15 cases without fibrosis (F0). Twelve healthy liver parenchyma samples were included as control. All samples were obtained from paraffin-embedded archival material. Micronucleated hepatocytes (MN-Heps) were analyzed through Feulgen/Fast-green staining. Results showed that the rates of MN-Heps in the F4 group were statistically significant (p < 0.05) and higher than those in the control group. Like results were also obtained on comparing F4 with F0, F1, F2 and F3 cases. Conversely, differences were not significant (p > 0.05) on comparing F0, F1, F2, F3, one against the other, as well as individual versus control. Although chromosomal losses in CH were detected, it was shown that liver parenchyma with fibrosis in the initial stages (F1-F3) cannot be considered cytogenetically abnormal. PMID:21637406

  13. Micronuclei assay and FISH analysis in human lymphocytes treated with six metal salts.

    PubMed

    Migliore, L; Cocchi, L; Nesti, C; Sabbioni, E

    1999-01-01

    The capability of some metal compounds for inducing micronuclei (MN) in human lymphocytes was studied. In this investigation, Al (III), Cd (II), Hg (II), Sb (V), Te (VI), and Tl (I) salts were considered. The FISH (fluorescence in situ hybridization) technique with a centromeric probe was coupled with the MN assay in binucleated cells in order to detect both centromere-positive MN (C+ MN) due to malsegregation phenomena and centromere-negative MN (C- MN) due to chromosome breakage. The blood of two young nonsmoking male donors was employed for all experiments. In both donors, all the tested metal compounds, with the exception of Tl(2)SO(4), showed a statistically significant increase of MN compared to controls, at least at one dose. FISH analysis revealed an increase in the fraction of C+ MN for Al, Cd, and Hg compounds, and of C- MN for the Sb salt; however, this was not a statistically significant increase. A different efficiency was observed for the different metal compounds, in particular, KSbO(3) and CH(3)HgCl, which were highly genotoxic, whereas the others showed minimal effects. Copyright 1999 Wiley-Liss, Inc.

  14. Oxidative stress enzyme status and frequency of micronuclei in heroin addicts in Turkey.

    PubMed

    Soykut, Buğra; Eken, Ayşe; Erdem, Onur; Akay, Cemal; Aydın, Ahmet; Çetin, Mustafa Kemal; Dilbaz, Nesrin

    2013-11-01

    Heroin is among the most widely used and dangerous addictive opiate. The World Health Organization (WHO) estimated that more than 15 million people are under the influence of opiate addiction. The aim of this study was to investigate copper zinc-superoxide dismutase (Cu,Zn-SOD), catalase (CAT) and selenium-dependent glutathione peroxidase (Se-GPx) antioxidant enzyme activities, malondialdehyde (MDA) levels and the frequency of micronuclei (MN) in addicts using heroin, the most commonly abused opiate in Turkey. Addicts were defined as individuals diagnosed according to "Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV)" criteria by the "Alcohol and Substance Abuse Treatment and Education Centre-Ankara (AMATEM)". The control group had no addiction. In comparisons between the groups, a significant decrease in Cu,Zn-SOD activity and increases in MDA levels and MN frequency were observed in addicts. It can be concluded that opiates may cause oxidative stress and that antioxidant supplementation, in addition to pharmacological and psychiatric approaches, can reduce the toxicological effects of these opiates.

  15. Frequencies of HPRT mutants and micronuclei in lymphocytes of cancer patients under chemotherapy: a prospective study.

    PubMed

    Tates, A D; van Dam, F J; Natarajan, A T; Zwinderman, A H; Osanto, S

    1994-05-01

    Fifteen cancer patients, including 10 testicular carcinoma patients, were treated with several types of combination chemotherapy. Blood samples were collected before, during and after chemotherapy. Subsequently, lymphocytes were analyzed for frequencies of HPRT mutants (MF) and micronuclei (MNF). Significantly elevated MFs were detected in eight patients. Mean expression time (+/- SD) for mutations was 98 +/- 54 days (range: 42-172 days). In some patients, enhanced MFs persisted for a period of 430-490 days after cessation of chemotherapy. In five patients MNFs were increased 2-6-fold and the enhancement was fairly persistent. Ifosfamide and cyclophosphamide appeared to be the most mutagenic and clastogenic constituents of the chemotherapy, while evidence for adverse effects of adriamycin, 4-epi-adriamycin and bleomycin was equivocal. Results indicate that the clinical use of mutagenic drugs must be weighed against the risks of persistent genetic damage and secondary malignancies in cured patients and their potential offspring. Further studies are necessary to determine the true risks and incidence of such abnormalities following chemotherapy for curable forms of cancer.

  16. Establishment of a Dose-response Curve for X-ray-Induced Micronuclei in Human Lymphocytes

    PubMed Central

    Lusiyanti, Yanti; Alatas, Zubaidah; Syaifudin, Mukh; Purnami, Sofiati

    2016-01-01

    The cytokinesis-block micronucleus assay in peripheral blood lymphocytes is an established technique for biodosimetry. The aim of this project was to generate a X-ray induced micronuclei (MN) curve for peripheral blood lymphocytes taken from five healthy donors. The blood samples were irradiated with X-rays of 122 KeV at a dose rate of 0.652 Gy/min to doses of 0.5, 1, 2, 3, and 4 Gy. The blood samples were then cultured for 72 h at 37°C and processed following the International Atomic Energy Agency standard procedure with slight modifications. The result showed that the yields of MN frequencies were increased with the increase of radiation dose. Reconstruction of the relationship of MN with dose was fitted to a linear-quadratic model using Chromosome Aberration Calculation Software version 2.0. Due to their advantages, mainly, the dependence on radiation dose and dose rate, despite their limitation, these curves will be useful as alternative method for in vitro dose reconstruction and can support the preparedness for public or occupational radiation overexposure and protection. The results reported here also give us confidence to apply the obtained calibration curve of MN for future biological dosimetry requirements in Indonesia. PMID:28217283

  17. Establishment of a Dose-response Curve for X-ray-Induced Micronuclei in Human Lymphocytes.

    PubMed

    Lusiyanti, Yanti; Alatas, Zubaidah; Syaifudin, Mukh; Purnami, Sofiati

    2016-01-01

    The cytokinesis-block micronucleus assay in peripheral blood lymphocytes is an established technique for biodosimetry. The aim of this project was to generate a X-ray induced micronuclei (MN) curve for peripheral blood lymphocytes taken from five healthy donors. The blood samples were irradiated with X-rays of 122 KeV at a dose rate of 0.652 Gy/min to doses of 0.5, 1, 2, 3, and 4 Gy. The blood samples were then cultured for 72 h at 37°C and processed following the International Atomic Energy Agency standard procedure with slight modifications. The result showed that the yields of MN frequencies were increased with the increase of radiation dose. Reconstruction of the relationship of MN with dose was fitted to a linear-quadratic model using Chromosome Aberration Calculation Software version 2.0. Due to their advantages, mainly, the dependence on radiation dose and dose rate, despite their limitation, these curves will be useful as alternative method for in vitro dose reconstruction and can support the preparedness for public or occupational radiation overexposure and protection. The results reported here also give us confidence to apply the obtained calibration curve of MN for future biological dosimetry requirements in Indonesia.

  18. Micronuclei and other nuclear anomalies in buccal epithelial cells of children with chronic kidney disease.

    PubMed

    Aykanat, Banu; Demircigil, Gonca Cakmak; Buyan, Necla; Baskin, Esra; Gulleroglu, Kaan; Fidan, Kibriya; Bayrakci, Umut Selda; Dalgic, Aydin; Karakayali, Hamdi; Haberal, Mehmet; Burgaz, Sema

    2016-12-01

    The objective of this study was to reveal the likely genomic instability in children with chronic kidney disease (CKD) using micronucleus (MN) assay on buccal epithelial cells (BEC). We investigated the frequencies of micronuclei and other nuclear anomalies, such as nuclear buds, binucleated cells, condensed chromatin, and karyorrhectic and pyknotic cells in BEC. Children with CKD were grouped as follows: children in the pre-dialysis (PreD) stage (N=17), children on regular haemodialysis (HD) (N=14), and children who have undergone transplantation (Tx) (N=17). As a control group, twenty age- and gender-matched healthy children were selected. The MN frequency in BEC of all groups of children with CKD was significantly elevated (5- to 7-fold) as compared to the control group (p<0.001). In contrast, the frequencies of nuclear buds were not significantly higher in the study groups compared to the control group. The frequencies of binucleated cells and condensed chromatin cells were significantly higher in all subgroups of children with CKD relative to the control group (p<0.001). Our results show that the BEC of pediatric PreD, HD, and Tx patients with CKD display increased cytogenetic, cytokinetic, and cytotoxic effects. They also point to the sensitivity and usefulness of the BEC MN assay in the assessment of genetic susceptibility of patients with CKD.

  19. Preimplantation paternal effects of acrylamide treatment on development and micronuclei formation in mice

    SciTech Connect

    Titenko-Holland, N.; Shang, N.; Smith, M.T.

    1997-10-01

    Treatment of male mice with acrylamide (AA, 50 mg/kg, 5 days) at postmeiotic stages of spermatogenesis was used to assess paternally mediated developmental and genetic toxicity in preimplantation embryos. There was a significant increase in the proportion of morphologically abnormal embryos (88.7 v 14.8%). The proliferation of morphologically normal embryos was significantly delayed, size of nuclei and number of cells were decreased, and fragmented nuclei were found in the majority of abnormal embryos (P<0.001). Cytogenetic damage was determined by the presence of micronuclei (MN) stained with DAPI or FISH with a pancentromeric probe. AA caused 10- and 20-fold increases in cells with MN in morphologically normal and abnormal embryos, respectively (41 and 93 MN per 1000 cells). There were no detectable effects of AA on size or ratio of centromere-positive MN. The presence of MN was not associated with the number or size of cells in the embryos. These findings suggest that multiple mechanisms are involved in male-mediated developmental and genetic toxicity of AA on preimplantation stages of embryogenesis. Future studies are needed to establish how preimplantation defects contribute to postimplantation and postnatal abnormalities.

  20. Micronuclei Induction in Human Fibroblasts Exposed In Vitro to Los Alamos High-Energy Neutrons

    NASA Technical Reports Server (NTRS)

    Gersey, Brad; Sodolak, John; Hada, Megumi; Saganti, Prem; Wilkins, Richard; Cucinotta, Francis; Wu, Honglu

    2006-01-01

    High-energy secondary neutrons, produced by the interaction of galactic cosmic rays with the atmosphere, spacecraft structure and planetary surfaces, contribute to a significant fraction to the dose equivalent in crew members and passengers during commercial aviation travel, and astronauts in space missions. The Los Alamos Nuclear Science Center (LANSCE) neutron facility#s ICE House 30L beamline is known to generate neutrons that simulate the secondary neutron spectra of earth#s atmosphere. The neutron spectrum is also similar to that measured onboard spacecraft like the MIR and International Space Station (ISS). To evaluate the biological damage, we exposed human fibroblasts in vitro to the LANSCE neutron beams without degrader at an entrance dose rate of 25 mGy/hr and analyzed the micronuclei (MN) induction. The cells were also placed behind a 9.9 cm water column to study effect of shielding in the protection of neutron induced damages. It was found that the dose response in the MN frequency was linear for the samples with and without shielding and the slope of the MN yield behind the shielding was reduced by a factor of 3.5. Compared to the MN induction in human fibroblasts exposed to a gamma source at a low dose rate, the RBE was found to be 16.7 and 10.0 for the neutrons without and with 9.9 cm water shielding, respectively.

  1. Beta-carotene prevents x-ray induction of micronuclei in human lymphocytes.

    PubMed

    Umegaki, K; Ikegami, S; Inoue, K; Ichikawa, T; Kobayashi, S; Soeno, N; Tomabechi, K

    1994-02-01

    The effects of beta-carotene and ascorbic acid on spontaneous and x-ray-induced appearance of micronuclei (MNs) in human lymphocytes were studied. For 12 d, three groups of healthy volunteers were given beta-carotene-deficient meals containing 100 mg ascorbic acid. There was no supplementation in the first 6 d but, in the last 6 d, the respective groups were given beta-carotene (30 mg), ascorbic acid (300 mg), or placebo. Blood samples were drawn on days 7 and 13 before breakfast, exposed either to x-ray irradiation or left unexposed and were cultured. Lymphocytes containing MNs were then counted. On day 7 the three groups showed comparable MN frequencies. On day 13 lymphocytes containing x-ray-induced MNs became less frequent in the beta-carotene but not the ascorbic acid group. Both before and after the supplementation, the MN frequency of irradiated lymphocytes showed a significant inverse correlation with plasma beta-carotene. These results strongly suggest that beta-carotene protects human lymphocytes from x-ray-induced genetic damage.

  2. Potential uses, limitations, and basic procedures of micronuclei and nuclear abnormalities in buccal cells.

    PubMed

    Torres-Bugarín, Olivia; Zavala-Cerna, María Guadalupe; Nava, Arnulfo; Flores-García, Aurelio; Ramos-Ibarra, María Luisa

    2014-01-01

    The use of biomarkers as tools to evaluate genotoxicity is increasing recently. Methods that have been used previously to evaluate genomic instability are frequently expensive, complicated, and invasive. The micronuclei (MN) and nuclear abnormalities (NA) technique in buccal cells offers a great opportunity to evaluate in a clear and precise way the appearance of genetic damage whether it is present as a consequence of occupational or environmental risk. This technique is reliable, fast, relatively simple, cheap, and minimally invasive and causes no pain. So, it is well accepted by patients; it can also be used to assess the genotoxic effect derived from drug use or as a result of having a chronic disease. Furthermore the beneficial effects derived from changes in life style or taking additional supplements can also be evaluated. In the present paper, we aim to focus on the explanation of MN test and its usefulness as a biomarker; we further give details about procedures to perform and interpret the results of the test and review some factors that could have an influence on the results of the technique.

  3. Induction of micronuclei in cultured mammalian cells by fume condensates of roofing asphalt.

    PubMed

    Qian, H W; Ong, T; Whong, W Z

    1996-05-01

    A considerable number of workers in the United States are employed in asphalt industries and are potentially exposed to asphalt fumes. The information regarding the potential carcinogenic hazards of such fumes to exposed workers is still limited. Studies have been conducted to determine the cytogenetic effects of roofing asphalt fume using cultured mammalian cells. Exponentially growing Chinese hamster lung fibroblasts (V79 cells) were exposed to different concentrations of condensates of type I and type III roofing asphalt fumes, generated at temperatures similar to actual roofing operation (316 +/- 10 degrees C). The frequencies of micronucleated cells in the treated and control cultures were determined. Additionally, immunofluorescent staining of kinetochore with human anti-kinetochore primary antibody and flouresceinated goat anti-human IgG was used to investigate the potential mechanism of micronucleus formation. The results show that both types of roofing asphalt fume condensates caused a significant increase in the frequency of micronucleated cells, and that 70% of micronucleated cells induced by asphalt fume condensates carried kinetochore-positive micronuclei. These findings indicate that both type I and type III roofing asphalt fumes are capable of causing principally cytogenetic damage by spindle apparatus alterations in cultured mammalian cells.

  4. Micronuclei Frequencies and Nuclear Abnormalities in Oral Exfoliated Cells of Nuclear Power Plant Workers

    PubMed Central

    Babannavar, Roopa; Lohra, Abhishek; Kodgi, Ashwin; Bapure, Sunil; Rao, Yogesh; J., Arun; Malghan, Manjunath

    2014-01-01

    Aim: Biomonitoring provides a useful tool to estimate the genetic risk from exposure to genotoxic agents. The aim of this study was to evaluate the frequencies of Micronuclei (MN) and other Nuclear abnormalities (NA) from exfoliated oral mucosal cells in Nuclear Power Station (NPS) workers. Materials and Methods: Micronucleus frequencies in oral exfoliated cells were done from individuals not known to be exposed to either environmental or occupational carcinogens (Group I). Similarly samples were obtained from full-time Nuclear Power Station (NPS) workers with absence of Leukemia and any malignancy (Group II) and workers diagnosed as leukemic patients and undergoing treatment (Group III). Results: There was statistically significant difference between Group I, Group II & Group III. MN and NA frequencies in Leukemic Patients were significantly higher than those in exposed workers &control groups (p < 0.05). Conclusion: MN and other NA reflect genetic changes, events associated with malignancies. Therefore, there is a need to educate those who work in NPS about the potential hazard of occupational exposure and the importance of using protective measures. PMID:25654022

  5. Micronuclei induction and chromosomal aberrations in Rattus norvegicus by chloroacetic acid and chlorobenzene.

    PubMed

    Faisal Siddiqui, Mohammad; Ahmad, Riaz; Ahmad, Waseem; Hasnain, Absar-ul

    2006-10-01

    Chloroacetic acid (CAA) and chlorobenzene (CB) have been evaluated for in vivo mutagenic potential in Rattus norvegicus, employing the following criteria : (i) chromosomal aberrations (CAs) such as breaks, gaps, exchanges, rings, and multiple aberrations and (ii) micronuclei (MN) induction. Three sublethal doses, 0.008, 0.01, and 0.012 mg/g b. wt. of CAA and 0.75, 1.0, and 1.25 mg/g b. wt. of rat of CB were administered and the bone marrow cells evaluated in each of the three treated groups at 12, 24, and 48 h, respectively. Mean MN frequencies of 4.40+/-0.2 and 5.42+/-0.3, obtained respectively for CAA and CB. The higher induction of MN by CAA and CB was dose- and time-dependent. Most significant impact (P<0.05) for either of the compounds was observed at 24h post administration, when the recorded mean frequency of CAs was maximum for CAA (4.33+/-0.6) as well as for CB (4.66+/-0.5).

  6. Induction of micronuclei and nuclear lesions in Channa punctatus following exposure to carbosulfan, glyphosate and atrazine.

    PubMed

    Nwani, Christopher Didigwu; Nagpure, Naresh Sahebrao; Kumar, Ravindra; Kushwaha, Basdeo; Kumar, Pavan; Lakra, Wazir Singh

    2014-10-01

    The genotoxic effects of commonly used agricultural pesticides viz., carbosulfan, glyphosate, and atrazine, were evaluated in Channa punctatus (Pisces, Perciformes) using micronucleus (MN) test and induction of nuclear lesions (NL). The 96 h LC50 value were estimated by probit analysis as 0.27, 32.0 and 42.0 mg L(-1), respectively, for carbosulfan, glyphosate, and atrazine using semi-static bioassays. Based on these values, three sublethal test concentrations of carbosulfan (0.07, 0.13, 0.20 mg L(-1)), glyphosate (8.1, 16.3, 24.4 mg L(-1)) and atrazine (10.6, 21.2, 31.8 mg L(-1)) corresponding to ¼, ½ and ¾ of the LC50 of the pesticides respectively, were selected for exposure for 96 h. Peripheral blood samplings were taken at intervals of 24 h for assessment of MN and NL frequencies. Considerably higher genotoxic damage was induced by carbosulfan as compared to glyphosate and atrazine. There were significant effects (p < 0.01) of concentrations in all the treated groups. The induction of MN and NL was highest at 96 h pesticide exposure at all test concentrations. The nuclear abnormalities recorded in this study, such as blebbed-, lobed-, notched- and bi-nuclei, other than micronuclei, are indicators of genotoxic damage.

  7. Induction of micronuclei in human fibroblasts across the Bragg curve of energetic heavy ions

    NASA Technical Reports Server (NTRS)

    Hada, Megumi; Rusek, Adam; Cucinotta, Francis A.; Wu, Honglu

    2006-01-01

    The space environment consists of a varying field of radiation particles including high energy ions, with spacecraft shielding material providing the major protection to astronauts from harmful exposure. Unlike low-L or X-rays, the presence of shielding does not always reduce the radiation risks for energetic charged particle exposure. Although the dose delivered by the charged particle increases sharply as the particle approaches the Bragg peak, the Bragg curve does not necessarily represent the biological damage along the particle traversal. The "biological Bragg curve" is dependent on the energy and the type of the primary particle, and may vary for different biological endpoints. To investigate "biological Bragg curves", we analyzed micronuclei (MN) induction along the particle traversal of Si and Fe ions at incident energies of 300 MeV/nucleon and 1 GeV/nucleon. A quantitative biological response curve did not reveal an increased yield of MN at the location of the Bragg peak. However, the ratio of mono-to bi-nucleated cells, which indicates inhibition in cell progression, increased at the Bragg peak location. These results confirm the hypothesis that "over kill" at the Bragg peak will affect the outcome of other biological endpoints.

  8. The Association of LINE-1 Hypomethylation with Age and Centromere Positive Micronuclei in Human Lymphocytes.

    PubMed

    Cho, Yoon Hee; Woo, Hae Dong; Jang, Yoonhee; Porter, Virginia; Christensen, Sonja; Hamilton, Raymond F; Chung, Hai Won

    2015-01-01

    Global hypomethylation in white blood cell (WBC) DNA has recently been proposed as a potential biomarker for determining cancer risk through genomic instability. However, the amplitude of the changes associated with age and the impacts of environmental factors on DNA methylation are unclear. In this study, we investigated the association of genomic hypomethylation with age, cigarette use, drinking status and the presence of centromere positive micronuclei (MNC+)-a biomarker for age-dependent genomic instability. Genomic hypomethylation of the repetitive element LINE-1 was measured in WBC DNA from 32 healthy male volunteers using the pyrosequencing assay. We also measured MNC+ with the micronucleus-centromere assay using a pan-centromeric probe. Possibly due to the small sample size and resulting low statistical power, smoking and drinking status had no significant effect on LINE-1 hypomethylation or the occurrence of MNC+. Consequently, we did not include them in further analyses. In contrast, LINE-1 hypomethylation and age significantly predicted MNC+; therefore, we examined whether LINE-1 hypomethylation plays a role in MNC+ formation by age, since genomic hypomethylation is associated with genomic instability. However, LINE-1 hypomethylation did not significantly mediate the effect of age on MNC+. Our data indicate that the repetitive element LINE-1 is demethylated with age and increasing MNC+ frequency, but additional studies are needed to fully understand the relation between genomic DNA hypomethylation, age and genomic instability.

  9. The Association of LINE-1 Hypomethylation with Age and Centromere Positive Micronuclei in Human Lymphocytes

    PubMed Central

    Cho, Yoon Hee; Woo, Hae Dong; Jang, Yoonhee; Porter, Virginia; Christensen, Sonja; Hamilton, Raymond F.; Chung, Hai Won

    2015-01-01

    Global hypomethylation in white blood cell (WBC) DNA has recently been proposed as a potential biomarker for determining cancer risk through genomic instability. However, the amplitude of the changes associated with age and the impacts of environmental factors on DNA methylation are unclear. In this study, we investigated the association of genomic hypomethylation with age, cigarette use, drinking status and the presence of centromere positive micronuclei (MNC+)—a biomarker for age-dependent genomic instability. Genomic hypomethylation of the repetitive element LINE-1 was measured in WBC DNA from 32 healthy male volunteers using the pyrosequencing assay. We also measured MNC+ with the micronucleus-centromere assay using a pan-centromeric probe. Possibly due to the small sample size and resulting low statistical power, smoking and drinking status had no significant effect on LINE-1 hypomethylation or the occurrence of MNC+. Consequently, we did not include them in further analyses. In contrast, LINE-1 hypomethylation and age significantly predicted MNC+; therefore, we examined whether LINE-1 hypomethylation plays a role in MNC+ formation by age, since genomic hypomethylation is associated with genomic instability. However, LINE-1 hypomethylation did not significantly mediate the effect of age on MNC+. Our data indicate that the repetitive element LINE-1 is demethylated with age and increasing MNC+ frequency, but additional studies are needed to fully understand the relation between genomic DNA hypomethylation, age and genomic instability. PMID:26196382

  10. Comparative studies on radiation-induced micronuclei and chromosomal aberrations in V79 cells

    SciTech Connect

    Keshava, C.; Ong., T. |; Nath, J.

    1994-12-31

    Induction of micronuclei (MN) and structural chromosomal aberrations (SCA) by physical agents extensively in a variety of cell lines for genotoxicity assessment. However, comparative data on the relationship between these two cytogenetic endpoints are limited. This study compares MN and SCA formation in V79 Chinese hamster lung cells treated with X-rays and UV radiation. Four replicate cultures of exponentially growing cells were exposed to four doses of X-rays (100 to 800 rad). For two replicate cultures, cytochalasin B (3 {mu}g/ml) was added and cells harvested 16 h later for MN and cell cycle kinetics assessments. For the remaining two replicate cultures, colcemid (0.025{mu}g/ml) was added 16 h post-treatment and harvested 2 h later for SCA and mitotic index (MI) analysis. This experiment was duplicated using four doses of UV radiation (100 to 800 {mu}joules x 10{sup 2}/cm{sup 2}). In the x-ray experiment, a dose-related decrease in the % of binucleated (BN) cells and MI was noted. Also, there was a clear dose-related increase in micronucleated binucleate (MNBN) and aberrant cells. Similar dose-response, but with lower frequencies, was observed in the UV radiation treatment. These data suggest that there is a good relationship between chromosome damage as measured by the % of MNBN and aberrant cells and cytotoxicity as measured by the % of BN cells and MI in these assays.

  11. Induction of micronuclei in human fibroblasts across the Bragg curve of energetic heavy ions

    NASA Technical Reports Server (NTRS)

    Hada, Megumi; Rusek, Adam; Cucinotta, Francis A.; Wu, Honglu

    2006-01-01

    The space environment consists of a varying field of radiation particles including high energy ions, with spacecraft shielding material providing the major protection to astronauts from harmful exposure. Unlike low-L or X-rays, the presence of shielding does not always reduce the radiation risks for energetic charged particle exposure. Although the dose delivered by the charged particle increases sharply as the particle approaches the Bragg peak, the Bragg curve does not necessarily represent the biological damage along the particle traversal. The "biological Bragg curve" is dependent on the energy and the type of the primary particle, and may vary for different biological endpoints. To investigate "biological Bragg curves", we analyzed micronuclei (MN) induction along the particle traversal of Si and Fe ions at incident energies of 300 MeV/nucleon and 1 GeV/nucleon. A quantitative biological response curve did not reveal an increased yield of MN at the location of the Bragg peak. However, the ratio of mono-to bi-nucleated cells, which indicates inhibition in cell progression, increased at the Bragg peak location. These results confirm the hypothesis that "over kill" at the Bragg peak will affect the outcome of other biological endpoints.

  12. Micronuclei in peripheral blood and bone marrow cells of mice exposed to 42 GHz electromagnetic millimeter waves.

    PubMed

    Vijayalaxmi; Logani, Mahendra K; Bhanushali, Ashok; Ziskin, Marvin C; Prihoda, Thomas J

    2004-03-01

    The genotoxic potential of 42.2 +/- 0.2 GHz electromagnetic millimeter-wave radiation was investigated in adult male BALB/c mice. The radiation was applied to the nasal region of the mice for 30 min/day for 3 consecutive days. The incident power density used was 31.5 +/- 5.0 mW/cm2. The peak specific absorption rate was calculated as 622 +/- 100 W/kg. Groups of mice that were injected with cyclophosphamide (15 mg/kg body weight), a drug used in the treatment of human malignancies, were also included to determine if millimeter-wave radiation exposure had any influence on drug-induced genotoxicity. Concurrent sham-exposed and untreated mice were used as controls. The extent of genotoxicity was assessed from the incidence of micronuclei in polychromatic erythrocytes of peripheral blood and bone marrow cells collected 24 h after treatment. The results indicated that the incidence of micronuclei in 2000 polychromatic erythrocytes was not significantly different among untreated, millimeter wave-exposed, and sham-exposed mice. The group mean incidences were 6.0 +/- 1.6, 5.1 +/- 1.5 and 5.1 +/- 1.3 in peripheral blood and 9.1 +/- 1.1, 9.3 +/- 1.6 and 9.1 +/- 1.6 in bone marrow cells, respectively. Mice that were injected with cyclophosphamide exhibited significantly increased numbers of micronuclei, 14.6 +/- 2.7 in peripheral blood and 21.3 +/- 3.9 in bone marrow cells (P< 0.0001). The drug-induced micronuclei were not significantly different in millimeter wave-exposed and sham-exposed mice; the mean incidences were 14.3 +/- 2.8 and 15.4 +/- 3.0 in peripheral blood and 23.5 +/- 2.3 and 22.1 +/- 2.5 in bone marrow cells, respectively. Thus there was no evidence for the induction of genotoxicity in the peripheral blood and bone marrow cells of mice exposed to electromagnetic millimeter-wave radiation. Also, millimeter-wave radiation exposure did not influence cyclophosphamide-induced micronuclei in either type of cells.

  13. Micronuclei in Bone Marrow and Liver in relation to Hepatic Metabolism and Antioxidant Response due to Coexposure to Chloroform, Dichloromethane, and Toluene in the Rat Model

    PubMed Central

    Belmont-Díaz, Javier; López-Gordillo, Ana Paulina; Molina Garduño, Eunice; Serrano-García, Luis; Coballase-Urrutia, Elvia; Cárdenas-Rodríguez, Noemí; Arellano-Aguilar, Omar; Montero-Montoya, Regina D.

    2014-01-01

    Genotoxicity in cells may occur in different ways, direct interaction, production of electrophilic metabolites, and secondary genotoxicity via oxidative stress. Chloroform, dichloromethane, and toluene are primarily metabolized in liver by CYP2E1, producing reactive electrophilic metabolites, and may also produce oxidative stress via the uncoupled CYP2E1 catalytic cycle. Additionally, GSTT1 also participates in dichloromethane activation. Despite the oxidative metabolism of these compounds and the production of oxidative adducts, their genotoxicity in the bone marrow micronucleus test is unclear. The objective of this work was to analyze whether the oxidative metabolism induced by the coexposure to these compounds would account for increased micronucleus frequency. We used an approach including the analysis of phase I, phase II, and antioxidant enzymes, oxidative stress biomarkers, and micronuclei in bone marrow (MNPCE) and hepatocytes (MNHEP). Rats were administered different doses of an artificial mixture of CLF/DCM/TOL, under two regimes. After one administration MNPCE frequency increased in correlation with induced GSTT1 activity and no oxidative stress occurred. Conversely, after three-day treatments oxidative stress was observed, without genotoxicity. The effects observed indicate that MNPCE by the coexposure to these VOCs could be increased via inducing the activity of metabolism enzymes. PMID:24949447

  14. Genotoxicity of nano/microparticles in in vitro micronuclei, in vivo comet and mutation assay systems

    PubMed Central

    Totsuka, Yukari; Higuchi, Takashi; Imai, Toshio; Nishikawa, Akiyoshi; Nohmi, Takehiko; Kato, Tatsuya; Masuda, Shuich; Kinae, Naohide; Hiyoshi, Kyoko; Ogo, Sayaka; Kawanishi, Masanobu; Yagi, Takashi; Ichinose, Takamichi; Fukumori, Nobutaka; Watanabe, Masatoshi; Sugimura, Takashi; Wakabayashi, Keiji

    2009-01-01

    Background Recently, manufactured nano/microparticles such as fullerenes (C60), carbon black (CB) and ceramic fiber are being widely used because of their desirable properties in industrial, medical and cosmetic fields. However, there are few data on these particles in mammalian mutagenesis and carcinogenesis. To examine genotoxic effects by C60, CB and kaolin, an in vitro micronuclei (MN) test was conducted with human lung cancer cell line, A549 cells. In addition, DNA damage and mutations were analyzed by in vivo assay systems using male C57BL/6J or gpt delta transgenic mice which were intratracheally instilled with single or multiple doses of 0.2 mg per animal of particles. Results In in vitro genotoxic analysis, increased MN frequencies were observed in A549 cells treated with C60, CB and kaolin in a dose-dependent manner. These three nano/microparticles also induced DNA damage in the lungs of C57BL/6J mice measured by comet assay. Moreover, single or multiple instillations of C60 and kaolin, increased either or both of gpt and Spi- mutant frequencies in the lungs of gpt delta transgenic mice. Mutation spectra analysis showed transversions were predominant, and more than 60% of the base substitutions occurred at G:C base pairs in the gpt genes. The G:C to C:G transversion was commonly increased by these particle instillations. Conclusion Manufactured nano/microparticles, CB, C60 and kaolin, were shown to be genotoxic in in vitro and in vivo assay systems. PMID:19725983

  15. Impact of p53 status on heavy-ion radiation-induced micronuclei in circulating erythrocytes

    NASA Technical Reports Server (NTRS)

    Chang, P. Y.; Torous, D.; Lutze-Mann, L.; Winegar, R.

    2000-01-01

    Transgenic mice that differed in their p53 genetic status were exposed to an acute dose of highly charged and energetic (HZE) iron particle radiation. Micronuclei (MN) in two distinct populations of circulating peripheral blood erythrocytes, the immature reticulocytes (RETs) and the mature normochromatic erythrocytes (NCEs), were measured using a simple and efficient flow cytometric procedure. Our results show significant elevation in the frequency of micronucleated RETs (%MN-RETs) at 2 and 3 days post-radiation. At 3 days post-irradiation, the magnitude of the radiation-induced MN-RET was 2.3-fold higher in the irradiated p53 wild-type animals compared to the unirradiated controls, 2.5-fold higher in the p53 hemizygotes and 4.3-fold higher in the p53 nullizygotes. The persistence of this radiation-induced elevation of MN-RETs is dependent on the p53 genetic background of the animal. In the p53 wild-type and p53 hemizygotes, %MN-RETs returned to control levels by 9 days post-radiation. However, elevated levels of %MN-RETs in p53 nullizygous mice persisted beyond 56 days post-radiation. We also observed elevated MN-NCEs in the peripheral circulation after radiation, but the changes in radiation-induced levels of MN-NCEs appear dampened compared to those of the MN-RETs for all three strains of animals. These results suggest that the lack of p53 gene function may play a role in the iron particle radiation-induced genomic instability in stem cell populations in the hematopoietic system.

  16. Micronuclei and other erythrocyte nuclear abnormalities in fishes from the Great Lakes Basin, USA.

    PubMed

    Braham, Ryan P; Blazer, Vicki S; Shaw, Cassidy H; Mazik, Patricia M

    2017-09-04

    Biological markers (biomarkers) sensitive to genotoxic and mutagenic contamination in fishes are widely used to identify exposure effects in aquatic environments. The micronucleus assay was incorporated into a suite of indicators to assess exposure to genotoxic and mutagenic contamination at five Great Lakes Areas of Concern (AOCs), as well as one non-AOC (reference) site. The assay allowed enumeration of micronuclei as well as other nuclear abnormalities for both site and species comparisons. Erythrocyte abnormality data was also compared to skin and liver tumor prevalence and hepatic transcript abundance. Erythrocyte abnormalities were observed at all sites with variable occurrence and severity among sites and species. Benthic-oriented brown bullhead (Ameiurus nebulosus) and white sucker (Catostomus commersonii) expressed lower rates of erythrocyte abnormalities, but higher rates of skin and liver neoplasms, when compared to pelagic-oriented largemouth bass (Micropterus salmoides) or smallmouth bass (Micropterus dolomieu) at the same site. The reduced erythrocyte abnormalities, increased transcript abundance associated with Phase I and II toxicant responsive pathways, and increased neoplastic lesions among benthic-oriented taxa may indicate the development of contaminant resistance of these species to more acute effects. Environ. Mol. Mutagen., 2017. © 2017 This article is a U.S. Government work and is in the public domain in the USA. Environmental and Molecular Mutagenesis published by Wiley Periodicals, Inc. on behalf of Environmental Mutagen Society. © 2017 This article is a U.S. Government work and is in the public domain in the USA. Environmental and Molecular Mutagenesis published by Wiley Periodicals, Inc. on behalf of Environmental Mutagen Society.

  17. Sister chromatid exchanges and micronuclei in peripheral lymphocytes of shoe factory workers exposed to solvents.

    PubMed Central

    Pitarque, Marià; Vaglenov, Alexander; Nosko, Maria; Pavlova, Sonya; Petkova, Vera; Hirvonen, Ari; Creus, Amadeu; Norppa, Hannu; Marcos, Ricard

    2002-01-01

    We examined sister chromatid exchanges (SCEs) and micronuclei (MN; cytokinesis-block method) in cultured peripheral lymphocytes from 52 female workers of two shoe factories and from 36 unexposed age- and sex-matched referents. The factory workers showed an elevated level of urinary hippuric acid, a biomarker of toluene exposure, and workplace air contained high concentrations of various organic solvents such as toluene, gasoline, acetone, and (in one of the plants only) ethylacetate and methylenediphenyl diisocyanate. The shoe factory workers showed a statistically significant higher frequency of micronucleated binucleate lymphocytes in comparison with the referents. This finding agreed with three preliminary MN determinations (each comprising 27-32 shoe workers and 16-20 controls) performed in one of the plants 2-5 years earlier. The shoe factory workers also had a lower average level of blood hemoglobin than the referents. In contrast, no difference was found between the groups in SCE analysis. Smokers showed significantly higher mean frequencies of SCEs per cell and high frequency cells (HFC) than nonsmokers. Aging was associated with increased MN rates and reduced cell proliferation. Polymorphism of the glutathione S-transferase M1 gene (GSTM1) did not affect the individual level of SCEs; but in smoking shoe workers an effect of the occupational exposure on the frequency of micronucleated cells could be seen only in GSTM1 null subjects. The low prevalence of the glutathione S-transferase T1 (GSTT1) null genotype precluded the evaluation of the influence of GSTT1 polymorphism. Our results show that the shoe factory workers have experienced genotoxic exposure, which is manifest as an increase in the frequency of MN, but not of SCEs, in peripheral lymphocytes. The exposures responsible for the MN induction could not be identified with certainty, but exposure to benzene in gasoline and methylenediphenyl diisocyanate may explain some of the findings. PMID:11940458

  18. A comparative study for selectivity of micronuclei in oral exfoliated epithelial cells

    PubMed Central

    Grover, S; Mujib, ABR; Jahagirdar, A; Telagi, N; Kulkarni, PG

    2012-01-01

    Background: Micronucleus (MN) represents small, additional nuclei formed by the exclusion of chromosome fragments or whole chromosomes lagging at mitosis. MN rates, therefore, indirectly reflect chromosome breakage or impairment of the mitotic apparatus. During the last few decades, micronuclei (“MNi”) in oral exfoliated epithelial cells are widely used as biomarkers of chromosomal damage, genome instability and cancer risk in humans. However, until now only little attention has been given to the effect of different staining procedures on the results of these MN assays. Aim: To compare the MNi frequencies in oral exfoliated epithelial cells using three different stains, i.e.,Feulgen stain, Papanicolaou stain (Pap) and hemotoxylin and eosin stain (H and E). Materials and Methods: Oral exfoliated cells from 45 cases of potentially malignant disorders (15 oral submucous fibrosis, 15 lichen planus and 15 leukoplakia) and 15 controls with healthy mucosa, were taken and MNi frequencies (No. of MNi/1000 cells) were compared using three different stains. Results: Mean MNi frequency in cases was found to be 3.8 with Feulgen stain, 16.8 with PAP and 25.9 with H and E. In controls, mean MNi frequency was 1.6 with Feulgen stain, 7.7 with PAP and 9.6 with H and E stain. Statistically significant value (P < 0.01) were observed when the three stains were compared together using Kruskal Walli's ANOVA test. Conclusion: Feulgen being a DNA-specific stain gave the least counts, although statistically significant results from the comparison of MNi frequency between cases and controls were obtained with all the three stains. PMID:23326025

  19. Metal nanoparticle-induced micronuclei and oxidative DNA damage in mice

    PubMed Central

    Song, Ming-Fen; Li, Yun-Shan; Kasai, Hiroshi; Kawai, Kazuaki

    2012-01-01

    Several mechanisms regarding the adverse health effects of nanomaterials have been proposed. Among them, oxidative stress is considered to be one of the most important. Many in vitro studies have shown that nanoparticles generate reactive oxygen species, deplete endogenous antioxidants, alter mitochondrial function and produce oxidative damage in DNA. 8-Hydroxy-2'-deoxyguanosine is a major type of oxidative DNA damage, and is often analyzed as a marker of oxidative stress in human and animal studies. In this study, we focused on the in vivo toxicity of metal oxide and silver nanoparticles. In particular, we analyzed the induction of micronucleated reticulocyte formation and oxidative stress in mice treated with nanoparticles (CuO, Fe3O4, Fe2O3, TiO2, Ag). For the micronucleus assay, peripheral blood was collected from the tail at 0, 24, 48 and 72 h after an i.p. injection of nanoparticles. Following the administration of nanoparticles by i.p. injection to mice, the urinary 8-hydroxy-2'-deoxyguanosine levels were analyzed by the HPLC-ECD method, to monitor the oxidative stress. The levels of 8-hydroxy-2'-deoxyguanosine in liver DNA were also measured. The results showed increases in the reticulocyte micronuclei formation in all nanoparticle-treated groups and in the urinary 8-hydroxy-2'-deoxyguanosine levels. The 8-hydroxy-2'-deoxyguanosine levels in the liver DNA of the CuO-treated group increased in a dose-dependent manner. In conclusion, the metal nanoparticles caused genotoxicity, and oxidative stress may be responsible for the toxicity of these metal nanoparticles. PMID:22573923

  20. Micronuclei and chromosome aberrations in subjects occupationally exposed to antineoplastic drugs: a multicentric approach.

    PubMed

    Moretti, Massimo; Grollino, Maria Giuseppa; Pavanello, Sofia; Bonfiglioli, Roberta; Villarini, Milena; Appolloni, Massimo; Carrieri, Mariella; Sabatini, Laura; Dominici, Luca; Stronati, Laura; Mastrangelo, Giuseppe; Barbieri, Anna; Fatigoni, Cristina; Bartolucci, Giovanni Battista; Ceretti, Elisabetta; Mussi, Francesca; Monarca, Silvano

    2015-08-01

    Recently published works showed that occupational exposure to antineoplastic drugs (ANPD) is still frequent in hospital settings, despite significant safety policy improvements. The aim of this study was to assess the current level of occupational exposure to ANPD and any potentially associated cytogenetic damages in hospital nurses routinely handling ANPD. Occupationally ANPD-exposed (n = 71) and ANPD-unexposed (n = 77; control) nurses were recruited on a voluntary basis from five hospitals in Northern and Central Italy. Evaluation of surface contamination and dermal exposure to ANPD was assessed by determining cyclophosphamide (CP) on selected surfaces (wipes) and on exposed nurses' clothes (pads). The concentration of unmetabolized CP—as a biomarker of internal dose—was measured in end-shift urine samples. Biomonitoring of genotoxic effects (i.e., biological effect monitoring) was conducted by analyzing micronuclei (MN) and chromosome aberrations (CA) in peripheral blood lymphocytes. Genetic polymorphisms for enzymes involved in metabolic detoxification (i.e., glutathione S-transferases) were analyzed as well. We observed a significant increase in MN frequency (5.30 ± 2.99 and 3.29 ± 1.97; mean values ± standard deviation; p < 0.0001) in exposed nurses versus controls, as well as in CA detection (3.30 ± 2.05 and 1.84 ± 1.67; p < 0.0001), exposed subjects versus controls. Our results provide evidence that, despite safety controlled conditions, ANPD handling still represents a considerable genotoxic risk for occupationally exposed personnel. Because both MN and CA have been described as being predictive of group-increased cancer risk, our findings point to a need for improving specific safety procedures in handling and administering ANPD.

  1. Elevated frequencies of micronuclei in pregnant women with type 1 diabetes mellitus and in their newborns.

    PubMed

    Witczak, Monika; Ferenc, Tomasz; Gulczyńska, Ewa; Nowakowska, Dorota; Łopaczyńska, Dobrosława; Wilczyński, Jan

    2014-03-15

    Pregestational diabetes mellitus (type 1 and type 2) affects about 1% of the obstetric population. In diabetes, persistent hyperglycemia can be a source of DNA damage via overproduction of reactive oxygen species (ROS). Using the cytokinesis-block micronucleus (CBMN) test, we measured the frequencies of micronuclei (MN) per 1000 binucleated (BN) cells in pregnant women (mothers) with type 1 diabetes mellitus (T1DM) and in their newborns. Peripheral blood lymphocytes were collected from 17 pregnant women with T1DM and cord-blood lymphocytes from their 17 newborns. The control group included 40 pregnant women (mothers) without diabetes mellitus (DM) and their 40 newborns. In the group of pregnant women with T1DM, the mean number of MN per 1000 BN cells was 2.35 (±1.07), significantly (p<0.001) higher than in the control group of pregnant women (0.86±0.90). The frequency value in the group of newborns of T1DM mothers was 1.42 (±0.60), significantly (p<0.05) higher than in the corresponding control group (0.67±0.79). The value in the group of mothers with T1DM was significantly (p<0.05) higher than in their newborns. Comparing mothers without DM with their newborns, no significant frequency differences were observed. No significant correlations were observed between MN frequencies in mothers with T1DM and either the frequencies in their newborns, the duration of diabetes, or HbA1C levels. Our results indicate that T1DM is accompanied by increased frequencies of MN in pregnant women and their newborns.

  2. Impact of p53 status on heavy-ion radiation-induced micronuclei in circulating erythrocytes

    NASA Technical Reports Server (NTRS)

    Chang, P. Y.; Torous, D.; Lutze-Mann, L.; Winegar, R.

    2000-01-01

    Transgenic mice that differed in their p53 genetic status were exposed to an acute dose of highly charged and energetic (HZE) iron particle radiation. Micronuclei (MN) in two distinct populations of circulating peripheral blood erythrocytes, the immature reticulocytes (RETs) and the mature normochromatic erythrocytes (NCEs), were measured using a simple and efficient flow cytometric procedure. Our results show significant elevation in the frequency of micronucleated RETs (%MN-RETs) at 2 and 3 days post-radiation. At 3 days post-irradiation, the magnitude of the radiation-induced MN-RET was 2.3-fold higher in the irradiated p53 wild-type animals compared to the unirradiated controls, 2.5-fold higher in the p53 hemizygotes and 4.3-fold higher in the p53 nullizygotes. The persistence of this radiation-induced elevation of MN-RETs is dependent on the p53 genetic background of the animal. In the p53 wild-type and p53 hemizygotes, %MN-RETs returned to control levels by 9 days post-radiation. However, elevated levels of %MN-RETs in p53 nullizygous mice persisted beyond 56 days post-radiation. We also observed elevated MN-NCEs in the peripheral circulation after radiation, but the changes in radiation-induced levels of MN-NCEs appear dampened compared to those of the MN-RETs for all three strains of animals. These results suggest that the lack of p53 gene function may play a role in the iron particle radiation-induced genomic instability in stem cell populations in the hematopoietic system.

  3. Micronuclei frequency in peripheral blood lymphocytes of cancer patients: a meta-analysis.

    PubMed

    Iarmarcovai, G; Ceppi, M; Botta, A; Orsière, T; Bonassi, S

    2008-01-01

    Micronuclei (MN) frequency is a biomarker of chromosomal damage, genome instability, and cancer risk that integrates acquired mutations and genetic susceptibility. To evaluate and summarize the evidence reporting association between cancer and MN formation, we performed a meta-analysis assessing the frequency of this biomarker in cancer patients. Findings from 37 publications were retrieved through an extensive search of the MedLine/PubMed database. Given the heterogeneity of the study design, all studies were re-classified into three groups: (i) baseline MN frequency of untreated cancer patients (25 studies), (ii) induced MN frequency in thyroid cancer patients undergoing radioiodine treatment (9 studies), and (iii) radiosensitivity of lymphocytes (12 studies) in untreated cancer patients. A meta-estimate of the frequency ratio (meta-FR) was computed in each group. A significant increase of MN frequency was found in untreated cancer patients (meta-FR=1.45; 95% Confidence Interval (95% CI): 1.28-1.64) and in thyroid cancer patients after radioiodine treatment (meta-FR=2.26; 95% CI: 1.90-2.68). The third meta-analysis showed a negative trend of meta-FR's when plotted vs. the dose used to study patients' radiosensitivity, possibly associated to a high rate of apoptosis. The results of this review substantiate the existing evidence about a role of MN in various steps of carcinogenesis. The relatively small numbers of papers suitable for the meta-analysis call for new and larger studies, possibly based on high-throughput techniques, to further understand the role of MN formation in the occurrence of genetic instability and cancer.

  4. Maternal diet and dioxin-like activity, bulky DNA adducts and micronuclei in mother-newborns.

    PubMed

    Pedersen, Marie; Halldorsson, Thorhallur I; Autrup, Herman; Brouwer, Abraham; Besselink, Harrie; Loft, Steffen; Knudsen, Lisbeth E

    2012-06-01

    Maternal diet can contribute to carcinogenic exposures and also modify effects of environmental exposures on maternal and fetal genetic stability. In this study, associations between maternal diet and the levels of dioxin-like plasma activity, bulky DNA adducts in white blood cells and micronuclei (MN) in lymphocytes from mother to newborns were examined. From 98 pregnant women living in the greater area of Copenhagen, Denmark in 2006-2007, maternal peripheral blood and umbilical cord blood were collected, together with information on health, environmental exposure and lifestyle. Maternal diet was estimated on the basis of maternal food frequency questionnaire (FFQ) completed by the end of pregnancy. Biomarkers were detected in paired blood samples through the dioxin-responsive chemical-activated luciferase expression (CALUX)(®) bioassay, (32)P-postlabelling technique and cytokinesis-block MN assay. Maternal preference for meats with dark surface were significantly associated with higher bulky DNA adducts in both maternal (β 95%CI; 0.46 (0.08, 0.84)) and cord blood (β 95%CI; 0.46 (0.05, 0.86)) before and after adjustment for potential confounders. No other significant associations between the 18 dietary variables and the biomarkers measured in maternal and fetal samples were identified. The present study suggests that maternal intake of meats with dark surface contributes to the bulky DNA adduct levels in maternal and umbilical cord blood. Relationship between food preparation and bulky DNA adducts appear to be captured by a FFQ while potential associations for other biomarkers might be more complex or need larger sample size.

  5. 6 ANEUPLOIDY TOLERANCE IN RHESUS MACAQUE PRE-IMPLANTATION EMBRYOS VIA MICRONUCLEI FORMATION, CELLULAR FRAGMENTATION, AND BLASTOMERE EXCLUSION.

    PubMed

    Daughtry, B L; Rosenkrantz, J L; Lazar, N; Redmayne, N; Nevonen, K A; Carbone, L; Chavez, S L

    2016-01-01

    A primary contributor to in vitro fertilization (IVF) failure is the presence of unbalanced chromosomes in pre-implantation embryos. Previous array-based and next-generation sequencing (NGS) studies determined that ~50 to 80% of human embryos are aneuploid at the cleavage stage. During early mitotic divisions, many human embryos also sequester mis-segregated chromosomes into micronuclei and concurrently undergo cellular fragmentation. We hypothesised that cellular fragmentation represents a response to mis-segregated chromosomes that are encapsulated into micronuclei. Here, we utilised the rhesus macaque pre-implantation embryo as a model to study human embryonic aneuploidy using a combination of Eeva(TM) time-lapse imaging for evaluating cell divisions, single-cell/-fragment DNA-Sequencing (DNA-Seq), and confocal microscopy of nuclear structures. Results from our time-lapse image analysis demonstrated that there are considerable differences in the timing of the first and third mitotic divisions between rhesus blastocysts and those that arrested before this stage in development (P<0.01; ANOVA). By examining the chromosome content of each blastomere from cleavage stage embryos via DNA-Seq, we determined that rhesus embryos have an aneuploidy frequency up to ~62% (N=26) with several embryos exhibiting chromosomal mosaicism between blastomeres (N=6). Certain blastomeres also exhibited reciprocal whole chromosomal gains or losses, indicating that these embryos had undergone mitotic non-disjunction early in development. In addition, findings of reciprocal sub-chromosomal deletions/duplications among blastomeres suggest that chromosomal breakage had occurred in some embryos as well. Embryo immunostaining for the nuclear envelope protein, LAMIN-B1, demonstrated that fragmented cleavage-stage rhesus embryos often contain micronuclei and that cellular fragments can enclose DNA. Our DNA-Seq analysis confirmed that cellular fragments might encapsulate whole and/or partial

  6. Micronuclei as biomarkers of carcinogen exposure in populations exposed to arsenic through drinking water in West Bengal, India: a comparative study in three cell types.

    PubMed

    Basu, Anamika; Ghosh, Pritha; Das, Jayanta K; Banerjee, Apurba; Ray, Kunal; Giri, Ashok K

    2004-05-01

    Contamination of groundwater by arsenic, a paradoxical human carcinogen, has become a cause of global public health concern. In West Bengal, India, the groundwater in 9 of 18 districts is heavily contaminated with arsenic. Various adverse health effects including cancer have been reported from these districts and are associated with prolonged arsenic exposure. A cross-sectional biomarker study was conducted to evaluate and compare the frequencies of micronuclei in peripheral blood lymphocytes, oral mucosa cells, and urothelial cells from the inhabitants of North 24 Parganas, one of the arsenic-affected districts. The three cell types were collected from 163 residents exposed to high levels of arsenic in drinking water (214.7213 +/- 9.0273 microg/l) and from 154 unexposed subjects residing in the unaffected East Midnapur district with very little or no exposure to arsenic through drinking water (9.2017 +/- 0.3157 microg/l). Our analysis revealed that micronuclei frequencies in the exposed group were significantly elevated to 5.33-fold over unexposed levels for lymphocytes, 4.63-fold for oral mucosa cells, and 4.71-fold for urothelial cells (increases in micronuclei frequencies significant at P < 0.01). The results indicate that chronic ingestion of arsenic in drinking water by the exposed subjects is linked to the enhanced incidence of micronuclei in all the three cell types, slightly higher level of micronuclei being observed in lymphocytes compared with oral mucosa and urothelial cells.

  7. In vitro RABiT measurement of dose rate effects on radiation induction of micronuclei in human peripheral blood lymphocytes

    PubMed Central

    Bertucci, Antonella; Smilenov, Lubomir B.; Turner, Helen C.; Amundson, Sally A.; Brenner, David J.

    2016-01-01

    Developing new methods for radiation biodosimetry has been identified as a high priority need in case of a radiological accident or nuclear terrorist attacks. A large-scale radiological incident would result in an immediate critical need to assess the radiation doses received by thousands of individuals. Casualties will be exposed to different doses and dose-rates due to their geographical position and sheltering conditions, and dose-rate is one of the principal factors that determine the biological consequences of a given absorbed dose. In these scenarios high-throughput platforms are required to identify the biological dose in a large number of exposed individuals for clinical monitoring and medical treatment. The RABiT (Rapid Automated Biodosimetry Tool) is designed to be completely automated from the input of blood sample into the machine to the output of a dose estimate. The primary goal of this paper was to quantify the dose-rate effects for RABiT-measured micronuclei in vitro in human lymphocytes. Blood samples from healthy volunteers were exposed in vitro to different doses of X-rays to acute and protracted doses over a period up to 24 hours. The acute dose (ADR) was delivered at ∼1.03Gy/min and the low dose rate (LDR) exposure at ∼0.31Gy/min. The results showed that the yield of micronuclei decreases with decreasing dose-rate starting at 2Gy, whereas response was indistinguishable from that of acute exposure in the low dose region, up to 0.5Gy. The results showed a linear-quadratic dose-response relationship for the occurrence of micronuclei for the acute exposure and a linear dose-response relationship for the low dose-rate exposure. PMID:26791381

  8. Micronuclei levels in mothers and their newborns from regions with different types of air pollution.

    PubMed

    Rossnerova, Andrea; Spatova, Milada; Pastorkova, Anna; Tabashidze, Nana; Veleminsky, Milos; Balascak, Ivan; Solansky, Ivo; Sram, Radim J

    2011-10-01

    The aim of this study was to analyze genetic damage in human lymphocytes measured using automated image analysis of micronuclei (MN) in a group of 178 mothers and their newborns from two locations in the Czech Republic. The concentrations of benzo[a]pyrene (B[a]P), particulate matter of aerodynamic diameter <2.5 μm (PM2.5) and benzene were measured by stationary monitoring in the winter season of 2008/2009 in the capital city of Prague and in Ceske Budejovice, a regional city in a rural area. The 3-month mean concentration of B[a]P before delivery was lower in Prague in comparison with Ceske Budejovice: 1.9 ± 0.5ng/m³ vs. 3.2 ± 0.2ng/m³ (p<0.001). The opposite trend was found for PM2.5 and benzene: 27.0 ± 2.5μg/m³ and 2.5 ± 0.5μg/m³ vs. 24.5 ± 0.7μg/m³ and 2.1 ± 0.8μg/m³ (p<0.001) for Prague vs. Ceske Budejovice, respectively. The average age of the mothers was 31 years (range, 18-49 years). The frequencies of MN per 1000 binucleated cells were 8.35 ± 3.06 vs. 6.47 ± 2.35 (p<0.001) for mothers from Prague and Ceske Budejovice, respectively, and 2.17 ± 1.32 vs. 3.82 ± 2.43 (p<0.001) for newborns from Prague and Ceske Budejovice, respectively. Other factors, including vitamin intake, exposure to tobacco smoke, body mass index (BMI) before pregnancy, the education level of the mothers and the impact of the mothers' and fathers' ages were analyzed in our study. The results suggest that the different sensitivity of the study groups to various mixtures of carcinogenic pollutants could be affected by significant differences in lifestyle factors. Possible higher genetic damage was analyzed in newborns of smoking mothers, and the birth weight of this group was 7.4% lower (p<0.05) in comparison with the newborns of nonsmoking mothers. No impact of the age of the mothers or fathers on MN frequency in the newborns was observed.

  9. Can Feulgen Stain be a Reliable Biomarker over PAP Stain for Estimation of Micronuclei Score?

    PubMed Central

    Prasad, Umesh Chandra; Chandolia, Betina; Manjunath, S M; Basu, Shiva; Verma, Silvie

    2016-01-01

    Introduction Malignant transformation of the Potentially Malignant Lesions (PML) in the oral cavity is associated with elevated mortality rate because of its aggressive and exceedingly invasive nature. Meticulous diagnosis and prompt therapy of PML may help prevent malignant conversion in oral lesions. Carcinogenic insult to oral cells results in chromosomal damage and formation of Micronuclei (Mn), before the development of clinical symptoms. Aim To determine the genotoxic effect of smoking and chewing tobacco on target tissue using Mn assay and to evaluate the prevalence of other nuclear anomalies associated with it and to determine the reliability of feulgen stain for Mn assay over Papaincolau (PAP) stain. Materials and Methods PAP and feulgen staining was done to study Mn in individuals who were having tobacco habits (smoking and chewing) without lesion (n=30), individuals who were having tobacco habit (smoking and chewing) with PML (n=30) and apparently healthy subjects (n=30). Data was analysed for statistical significance using SPSS 17.0 by Kruskal - Wallis Test and Bonferronii test. Results Tobacco habits in the form of smoking and chewing have mutagenic effects on human chromosomes which is indicated by increased frequency of Mn in oral exfoliative cells. The mean Mn frequency using feulgen stain was found to be 12.27 with lesion, 10.23 with without lesion and 3.87 in controls. Whereas, metanucleated analysis revealed no significant correlation with the formation of Mn. Non-specific DNA stain (PAP) showed high numbers of Mn cells in all the groups compared to feulgen. Statistically significant difference (p<0.0001) was observed when both the stains were compared for Mn numbers. Conclusion These findings indicate that the individuals having tobacco habits (smoking and chewing) with lesion have high number of Mn cells, thus supporting the assay to be used as a reliable biomarker to assess the genotoxic effect of tobacco in the oral mucosa. The reason for

  10. Baseline values of micronuclei and comet assay in the lizard Tupinambis merianae (Teiidae, Squamata).

    PubMed

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

    2012-10-01

    The Micronucleus test (MN) and Comet assay (CA) are currently the most widely used methods that allow the characterization of DNA damage induced by physical and chemical agents in wild species. The continuous expansion of the cultivated areas in Argentina, since the introduction of transgenic crops, mainly soy, in association with the increased use of pesticides, transformed deeply the natural environments where the lizard Tupinambis merianae (tegu lizard) occurs. Despite the fact that reptiles have shown to be excellent bioindicators of environmental contaminants, there is no record of genotoxicity studies in T. merianae. The aim of the present study was to adjust the MN test and CA protocols to be applied in erythrocytes of T. merianae, and determine the baseline values of DNA damage in this species. We used 20 adult lizards (10 males: 10 females) from Estación Zoológica Experimental "Granja La Esmeralda" (Santa Fe, Argentina). Peripheral blood samples were collected from all animals and the MN test and CA applied according to the protocols established for other reptilian species. We test critical parameters of CA protocol (cell density, unwinding and electrophoresis times) using increasing concentrations of H2O2 (10, 25 and 50 μM) as a known genotoxic agent to induce DNA damage. Based on this, we determined the most suitable conditions for the CA in this species: a cell density of 4×10(3) erythrocytes per slide, 10 min of unwinding and 15 min of electrophoresis at 0.90 V/cm approximately. The baseline frequency of micronuclei (BFMN=MN/1000 erythrocytes counted) determined for this species was 0.95±0.27 and the basal damage index (BDI: calculated from 100 comet images classified in arbitrary units)=103.85±0.97. No differences were observed between sexes in the BFMN or BDI (p>0.05), and no relation was found between baseline values and length or weight of the analyzed animals (p>0.05). These results demonstrated the sensitivity of both biomarkers of

  11. Analysis of mutations and bone marrow micronuclei in Big Blue rats fed leucomalachite green.

    PubMed

    Manjanatha, M G; Shelton, S D; Bishop, M; Shaddock, J G; Dobrovolsky, V N; Heflich, R H; Webb, P J; Blankenship, L R; Beland, F A; Greenlees, K J; Culp, S J

    2004-03-22

    Leucomalachite green (LMG) is the major metabolite of malachite green (MG), a triphenylmethane dye that has been used widely as an antifungal agent in the fish industry. Concern over MG and LMG is due to the potential for consumer exposure, suggestive evidence of tumor promotion in rodent liver, and suspicion of carcinogenicity based on structure-activity relationships. In order to evaluate the risks associated with exposure to LMG, female Big Blue rats were fed up to 543 ppm LMG; groups of these rats were killed after 4, 16, or 32 weeks of exposure and evaluated for genotoxicity. We previously reported that this treatment resulted in a dose-dependent induction of liver DNA adducts, and that the liver lacI mutant frequency (MF) was increased, but only in rats fed 543 ppm LMG for 16 weeks. In the present study, we report the results from lymphocyte Hprt mutant assays and bone marrow micronucleus assays performed on these same rats. In addition, we have determined the types of lacI mutations induced in the rats fed 543 ppm LMG for 16 weeks and the rats fed control diet. No significant increases in the frequency of micronuclei or Hprt mutants were observed for any of the doses or time points assayed. Molecular analysis of 80 liver lacI mutants from rats fed 543 ppm LMG for 16 weeks revealed that 21% (17/80) were clonal in origin and that most (55/63) of the independent mutations were base pair substitutions. The predominant type of mutation was G:C --> A:T transition (31/63) and the majority (68%) of these involved CpG sites. When corrected for clonality, the 16-week lacI mutation frequency (36 +/- 10) x 10(-6) in treated rats was not significantly different from the clonally corrected control frequency (17 +/- 9 x 10(-6); P = 0.06). Furthermore, the lacI mutational spectrum in treated rats was not significantly different from that found for control rats (P = 0.09). Taken together, these data indicate that the DNA adducts produced by LMG in female rats do not result

  12. Effects of inhibitors of DNA, RNA and protein synthesis on frequencies and types of premature chromosome condensation from X-ray induced micronuclei.

    PubMed

    Madle, S; Nowak, J; Obe, G

    1976-10-28

    Cells containing X-ray induced micronuclei were treated for a few hours before fixation with inhibitors of DNA synthesis (cytosine arabinoside; azathioprine; thymidine; trenimon), of RNA synthesis (actinomycin D; ethidium bromide), and of protein synthesis (puromycin). Only the inhibitors of DNA synthesis lead to a significant suppression of the frequencies of mitoses with micronucleus derived premature chromosome condensation (PCC). We tend to interprete the result as follows: Micronuclei that are in the G1 phase of their cell cycles are accumulated at the G1/S border or in the early S phase of their cell cycles under the influence of the inhibitors of the DNA synthesis. Micronuclei blocked in this way cannot be induced to undergo PCC and seem to disappear from the cells.

  13. Water mutagenic potential assessment on a semiarid aquatic ecosystem under influence of heavy metals and natural radioactivity using micronuclei test.

    PubMed

    Chaves, Luiz Cláudio Cardozo; Navoni, Julio Alejandro; de Morais Ferreira, Douglisnilson; Batistuzzo de Medeiros, Silvia; Ferreira da Costa, Thomas; Petta, Reinaldo Antônio; Souza do Amaral, Viviane

    2016-04-01

    The contamination of water bodies by heavy metals and ionizing radiation is a critical environmental issue, which can affect water quality and, thus, human health. This study aimed to evaluate the water quality of the Boqueirão de Parelhas Dam in the Brazilian semiarid region. A 1-year study (2013-2014) was performed through the assessment of physicochemical parameters, heavy metal content, and radioactivity along with the mutagenicity potential of water using micronuclei test in Orechromis niloticus (in vivo) and the cytokinesis-block micronucleus (CBMN) assay in human lymphocytes (in vitro). A deterioration of water organoleptics characteristics by the presence of high levels of sulfate and total solids was observed. High concentrations of aluminum, nickel, silver, and lead along with the alpha particle content were higher than the limits suggested by the World Health Organization and Brazilian legislation for drinking water. An increase in the frequency of micronuclei and nuclear abnormalities was observed in both experimental models. The results obtained confirmed the mutagenic potential present in water samples. This study highlights that geogenic agents affect water quality becoming a human health concern to be taken into account due to the relevance that this water reservoir has in the region.

  14. Elevated Frequencies of Micronuclei and other Nuclear Abnormalities of Chrome Plating Workers Occupationally Exposed to Hexavalent Chromium

    PubMed Central

    Sudha, S; Kripa, SK; Shibily, P; Shyn, J

    2011-01-01

    Background Biomonitoring provides a useful tool to estimate the genetic risk from exposure to genotoxic agents. The aim of this study was to assess the potential cytogenetic damage associated with occupational exposure to hexavalent chromium by using micronuclei (MN) as a biomarker. Methods This was a cross-sectional study and all participants were males. Both the exposed and control individuals were selected from Coimbatore, Southern India. Exfoliated buccal cells from 44 chrome plating workers and 40 age and sex matched control subjects were examined for MN frequency and nuclear abnormalities (NA) other than micronuclei, such as binucleates, broken eggs, karyorrhexis, karyolysis and pyknosis. Results Results showed statistically significant difference between chrome plating workers and control groups. MN and NA frequencies in chrome plating workers were significantly higher than those in control groups (p < 0.05) and also significantly related to smoking habit (P < 0.05). A significant difference in NA was observed in workers exposed to chromium for longer duration. In addition to this, a higher degree of NA was observed among smokers. Conclusion MN and other NA reflect genetic changes, events associated with carcinogenesis. Therefore the results of this study indicate that chrome plating workers are under risk of significant cytogenetic damage. Therefore, there is a need to educate those who work with heavy metals about the potential hazard of occupational exposure and the importance of using protective measures. PMID:26328050

  15. Hyperbaric oxygen pretreatment according to the gas micronuclei denucleation hypothesis reduces neurologic deficit in decompression sickness in rats.

    PubMed

    Katsenelson, K; Arieli, R; Arieli, Y; Abramovich, A; Feinsod, M; Tal, D

    2009-08-01

    During sudden or too rapid decompression, gas is released within supersaturated tissues in the form of bubbles, the cause of decompression sickness. It is widely accepted that these bubbles originate in the tissue from preexisting gas micronuclei. Pretreatment with hyperbaric oxygen (HBO) has been hypothesized to shrink the gas micronuclei, thus reducing the number of emerging bubbles. The effectiveness of a new HBO pretreatment protocol on neurologic outcome was studied in rats. This protocol was found to carry the least danger of oxygen toxicity. Somatosensory evoked potentials (SSEPs) were chosen to serve as a measure of neurologic damage. SSEPs in rats given HBO pretreatment before a dive were compared with SSEPs from rats not given HBO pretreatment and SSEPs from non-dived rats. The incidence of abnormal SSEPs in the animals subjected to decompression without pretreatment (1,013 kPa for 32 min followed by decompression) was 78%. In the pretreatment group (HBO at 304 kPa for 20 min followed by exposure to 1,013 kPa for 33 min and decompression) this was significantly reduced to 44%. These results call for further study of the pretreatment protocol in higher animals.

  16. Effect of space flight on the frequency of micronuclei and expression of stress-responsive proteins in cultured mammalian cells.

    PubMed

    Ikenaga, Mituo; Hirayama, Jun; Kato, Tomohisa; Kitao, Hiroyuki; Han, Zhen-Bo; Ishizaki, Kanji; Nishizawa, Kimiko; Suzuki, Fumio; Cannon, Thomas F; Fukui, Keiji; Shimazu, Toru; Kamigaichi, Shigeki; Ishioka, Noriaki; Matsumiya, Hiroyuki

    2002-12-01

    Results of past space experiments suggest that the biological effect of space radiation could be enhanced under microgravity in some cases, especially in insects. To examine if such a synergistic effect of radiation and microgravity also exists in human cells, frequencies of chromosome instability and cellular levels of several stress-responsive proteins were analyzed in cultured human and rodent cells after space flight. Human (MCF7 and AT2KY), mouse (m5S) and hamster (SHE) cell lines were loaded on the Space Shuttle Discovery (STS-95 mission) and grown during a 9-day mission. After landing, the micronuclei resulting from abnormal nuclear division and accumulation of stress-responsive proteins such as p53 and mitogen-activated protein kinases (MAPKs), which are involved in radiation-induced signal transduction cascades, were analyzed. The frequencies of micronuclei in all the four mammalian cell strains tested were not significantly different between flight and ground control samples. Also, the cellular amounts of p53, p21 (WAF1/SDI1/CIP1) and activated (phosphorylated) forms of three distinct MAPKs in MCF7 and m5S cells of flight samples were similar to those of ground control samples. These results indicated that any effect of space radiation, microgravity, or combination of both were not detectable, at least under the present experimental conditions.

  17. Construction of dose response calibration curves for dicentrics and micronuclei for X radiation in a Serbian population.

    PubMed

    Pajic, J; Rakic, B; Jovicic, D; Milovanovic, A

    2014-10-01

    Biological dosimetry using chromosome damage biomarkers is a valuable dose assessment method in cases of radiation overexposure with or without physical dosimetry data. In order to estimate dose by biodosimetry, any biological dosimetry service have to have its own dose response calibration curve. This paper reveals the results obtained after irradiation of blood samples from fourteen healthy male and female volunteers in order to establish biodosimetry in Serbia and produce dose response calibration curves for dicentrics and micronuclei. Taking into account pooled data from all the donors, the resultant fitted curve for dicentrics is: Ydic=0.0009 (±0.0003)+0.0421 (±0.0042)×D+0.0602 (±0.0022)×D(2); and for micronuclei: Ymn=0.0104 (±0.0015)+0.0824 (±0.0050)×D+0.0189 (±0.0017)×D(2). Following establishment of the dose response curve, a validation experiment was carried out with four blood samples. Applied and estimated doses were in good agreement. On this basis, the results reported here give us confidence to apply both calibration curves for future biological dosimetry requirements in Serbia. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Induction of micronuclei and alteration of gene expression by an organomodified clay in HepG2 cells.

    PubMed

    Maisanaba, Sara; Hercog, Klara; Ortuño, Natalia; Jos, Ángeles; Žegura, Bojana

    2016-07-01

    Clay2 is an organomodified montmorillonite developed by the Technological Institute of Packaging, Transport and Logistic (ITENE) in order to improve polymeric materials used in food packaging. There is not much known on Clay2 toxic potential, particularly at DNA level, therefore it is mandatory to assess its toxicity prior to its commercialization. In the present study the human hepatoma cell line (HepG2) was exposed to non-cytotoxic concentrations of Clay2 and the genomic stability was studied with the Cytokinesis block micronucleus cytome assay, by determining the formation of micronuclei (MN), nucleoplasmic bridges (NPBs) and nuclear buds (NBUDs). Moreover, the expression of various genes involved in the mechanisms of its action using the real-time quantitative PCR was studied. The results obtained provide the evidence that Clay2 is potentially genotoxic as it increased the frequency of micronuclei. In addition it deregulated genes involved in the metabolism, immediate-early response/signaling, DNA damage and oxidative stress showing new valuable information on the cellular response to Clay2. Nonetheless, further studies are highly needed to elucidate the molecular mechanisms of clays toxicity.

  19. Apoptosis and micronuclei induction in human epithelial cells exposed to energetic carbon ions in the Bragg peak region

    NASA Astrophysics Data System (ADS)

    Emami, K.; Hada, M.; Lacy, S.; Clement, J.; Rusek, A.; Cucinotta, F. A.; Wu, H.

    Space radiation is a complex mixture of charged particles from solar and galactic origins. Many of these high energy charged particles can penetrate current spacecraft shielding and produce secondary particles, creating significant health hazard. Therefore, understanding the biological effects of these particles along the particle traversal is critical in optimizing new shielding designs. Here, we studied DNA damage on monolayer culture of mammary epithelial cell line irradiated by 290 MeV/nucleon carbon ions. Frequencies of apoptosis and micronuclei (MN) induction were scored across the Bragg curve at entrance radiation doses of 0.5 and 2 Gy. The results for both doses show that the peak of apoptosis yield coincides with the physical Bragg peak. However, the peak location for the MN frequency appears to be dose dependent. We argue that the presence of a higher proportion of micronuclei prior to the Bragg peak at the higher radiation dose is the consequence of "overkill" at the physical Bragg peak location. Results of the carbon exposure were compared with the data for the same cell type exposed to γ-rays.

  20. Detection of micronuclei, cell proliferation and hyperdiploidy in bladder epithelial cells of rats treated with o-phenylphenol.

    PubMed

    Balakrishnan, S; Uppala, P T; Rupa, D S; Hasegawa, L; Eastmond, D A

    2002-01-01

    o-Phenylphenol (OPP), a widely used fungicide and antibacterial agent, has been considered to be among the top 10 home and garden pesticides used in the USA. Earlier studies have consistently shown that the sodium salt of OPP (SOPP) causes bladder cancer in male Fischer 344 (F344) rats, whereas OPP has produced variable results. This difference has been attributed to the presence of the sodium salt. To determine cellular and genetic alterations in the rat bladder and the influence of the sodium salt, F344 rats were administered 2% OPP, 2% NaCl and 2% NaCl + 2% OPP in their diet for 14 days. Twenty-four hours before being killed the animals were administered 5-bromo-2'-deoxyuridine (BrdU) by i.p. injection. Bladder cells were isolated, stained with DAPI and scored for the presence of micronuclei and incorporation of BrdU into replicating cells. To determine changes in chromosome number, we used fluorescence in situ hybridization (FISH) with a DNA probe for rat chromosome 4. Significant increases in the frequency of micronuclei and BrdU incorporation were seen in bladder cells of rats from all treatment groups. In contrast, the frequency of hyperdiploidy/polyploidy in treated animals was not increased over that seen in controls. A high control frequency of cells with three or more hybridization signals was seen, probably due to the presence of polyploid cells in the bladder. The presence of polyploid cells combined with cytotoxicity and compensatory cell proliferation makes it difficult to determine whether OPP is capable of inducing aneuploidy in the rat urothelium. In summary, these studies show that OPP can cause cellular and chromosomal alterations in rat bladder cells in the absence of the sodium salt. These results also indicate that at high concentrations the sodium salt can enhance chromosomal damage in the rat urothelium.

  1. Evaluation of Genotoxicity in Automobile Mechanics Occupationally Exposed to Polycyclic Aromatic Hydrocarbons Using Micronuclei and Other Nuclear Abnormalities

    PubMed Central

    Khan, Mohammed Rafiq; Sudha, Sellappa

    2012-01-01

    Background Occupational and environmental exposures mostly represent mixtures of genotoxic agents, whereas the specificity of biomarker measurements varies widely. Exploration of correlations among biomarkers contributes to the further progress of molecular cancer epidemiology and to the selection of the optimal biomarkers for the investigation of human exposure to carcinogens. The aim of this study was to assess the potential cytogenetic damage associated with occupational exposure to Polycyclic Aromatic Hydrocarbons (PAHs) among automobile mechanics by using Micronuclei (MN) and other Nuclear Abnormalities (NA) as a biomarker. Methods The study population composed of 110 occupationally exposed automobile mechanics and 100 unexposed controls. All the study participants were males. Both the exposed and control individuals were selected from automobile garages located in the urban area of Coimbatore City, South India. Exfoliated buccal cells were collected from 110 automobile mechanics and 100 age and sex matched controls. Further, cells were examined for MN frequency and Nuclear Abnormalities (NA) other than micronuclei, such as binucleates, broken eggs and karyolysis. Results Results showed a statistically significant difference between occupationally exposed automobile mechanics and control groups. MN and NA frequencies in automobile mechanics were significantly higher than those in control groups (p < 0.05) and also significantly related to smoking habit (p < 0.05). In addition, a higher degree of NA was observed among the exposed subjects with smoking, drinking, tobacco chewing, which is an indicative of cytogenetic damage in these individuals. Conclusion MN and other NA reflect genetic changes, events associated with carcinogenesis. Therefore, the results of this study indicate that automobile mechanics exposed to PAHs are under risk of significant cytogenetic damage. Therefore, it is important to provide and offer better awareness of occupational hazards

  2. Mitotic slippage underlies the relationship between p53 dysfunction and the induction of large micronuclei by colcemid.

    PubMed

    Hashimoto, Kiyohiro; Todo, Takeshi

    2013-07-01

    Micronuclei induced by aneugens are larger than those induced by clastogens in both in vitro and in vivo micronucleus (MN) assays. p53 dysfunction increases the formation of large micronuclei following treatment with aneugens; this study sought to identify the mechanisms responsible for this. Treatment with colcemid, both a mitotic inhibitor and an aneugen, induced MN containing two or more chromosomes more frequently in NH32 cells, in which p53 function is compromised, than in TK6 cells, in which p53 is functional. This indicates that p53 dysfunction enhances aneugen-induced chromosome loss or perturbs apoptosis, resulting in the formation of large MN. To examine the former hypothesis, the incidence of chromosome malsegregation in colcemid-treated TK6 and NH32 cells was compared using the cytokinesis-block MN assay. The incidence of chromosome non-disjunction was higher in NH32 cells than in TK6 cells, whereas the incidence of MN containing two or more chromosomes was similar between the two cell lines. To address the involvement of apoptosis in cell cycle progression, examination of chromosome 8 distribution revealed that more mononuclear NH32 than TK6 cells were tetraploid after prolonged mitotic inhibition, which indicated that the more number of NH32 cells may have bypassed the spindle assembly checkpoint via mitotic slippage and progression into the next interphase. Cells that underwent mitotic slippage were likely to contain lagging chromosomes formed via chromosome malsegregation, resulting in MN separated from the main nucleus. The number of TK6 cells containing large MN following colcemid treatment was increased by treatment with a caspase inhibitor in a dose-dependent manner, indicating that TK6 cells with MN normally undergo apoptosis. In conclusion, these findings indicate that mitotic slippage and perturbed apoptosis contribute to the induction of large MN in p53-compromised cells following treatment with colcemid.

  3. Increased Susceptibility to Methotrexate-Induced Toxicity in Nonalcoholic Steatohepatitis

    PubMed Central

    Hardwick, Rhiannon N.; Clarke, John D.; Lake, April D.; Canet, Mark J.; Anumol, Tarun; Street, Stephanie M.; Merrell, Matthew D.; Goedken, Michael J.; Snyder, Shane A.; Cherrington, Nathan J.

    2014-01-01

    Hepatic drug metabolizing enzymes and transporters play a crucial role in determining the fate of drugs, and alterations in liver function can place individuals at greater risk for adverse drug reactions (ADRs). We have shown that nonalcoholic steatohepatitis (NASH) leads to changes in the expression and localization of enzymes and transporters responsible for the disposition of numerous drugs. The purpose of this study was to determine the effect of NASH on methotrexate (MTX) disposition and the resulting toxicity profile. Sprague Dawley rats were fed either a control or methionine-choline-deficient diet for 8 weeks to induce NASH, then administered a single ip vehicle, 10, 40, or 100 mg/kg MTX injection followed by blood, urine, and feces collection over 96 h with terminal tissue collection. At the onset of dosing, Abcc1–4, Abcb1, and Abcg2 were elevated in NASH livers, whereas Abcc2 and Abcb1 were not properly localized to the membrane, similar to that previously observed in human NASH. NASH rodents receiving 40–100 mg/kg MTX exhibited hepatocellular damage followed by initiation of repair, whereas damage was absent in controls. NASH rodents receiving 100 mg/kg MTX exhibited slightly greater renal toxicity, indicating multiple organ toxicity, despite the majority of the dose being excreted by 6 h. Intestinal toxicity in NASH however, was strikingly less severe than controls, and coincided with reduced fecal MTX excretion. Because MTX-induced gastrointestinal toxicity limits the dose escalation necessary for cancer remission, these data suggest a greater risk for life-threatening MTX-induced hepatic and renal toxicity in NASH in the absence of overt gastrointestinal toxicity. PMID:25080921

  4. Methotrexate-induced misincorporation of uracil into DNA

    PubMed Central

    Goulian, M.; Bleile, B.; Tseng, B. Y.

    1980-01-01

    A line of human lymphoid cells was tested for the presence of dUMP in DNA with or without treatment with the dihydrofolate reductase inhibitor, methotrexate. Cells treated with methotrexate and labeled with [3H]dUrd contained dUMP in DNA in readily detectable amounts (≈0.8 pmol of dUMP per μmol of total DNA nucleotide), and this was increased ≈3-fold if the cells were also treated with Ura at the same time. No dUMP (<1 fmol/μmol of DNA) could be detected by these methods in DNA from cells not treated with methotrexate, regardless of whether Ura was present or absent. The presence of dUMP in DNA from cells treated with methotrexate is a result of the great increase in intracellular concentration of dUTP and the fall in dTTP that accompany inhibition of thymidylate synthetase (5,10-methylenetetrahydrofolate:dUMP C-methyltransferase; EC 2.1.1.45) by the drug. These changes are apparently sufficient to overcome the normal mechanisms that exclude dUMP from DNA, and the enhancement by Ura reflects suppression of one of the mechanisms, Ura removal from DNA by the enzyme Ura-DNA glycosylase. The results suggest an active lesion of DNA in cells in which thymidylate synthetase is inhibited. Under these conditions there appears to be a cyclic incorporation and removal of dUMP resulting from reinsertion of dUMP during gap repair at sites of Ura removal. This consequence of the normal excision-repair process, which occurs when intracellular levels of dUTP approach those of dTTP, may have effects related to the cytotoxicity of drug inhibitors of thymidylate synthetase, clinical deficiencies of folate and vitamin B-12, and thymineless death, in general. Images PMID:6929529

  5. Hepatoprotective effect of sitagliptin against methotrexate induced liver toxicity

    PubMed Central

    Abo-Haded, Hany M.; Elkablawy, Mohamed A.; Al-johani, Zeyad; Al-ahmadi, Osama; El-Agamy, Dina S.

    2017-01-01

    Sitagliptin is selective dipeptidyl peptidase-4 inhibitor (DPP4-I), used clinically as a new oral anti-diabetic agent. This study explored the underlying mechanisms of the hepatoprotective role of sitagliptin pretreatment against methotrexate (MTX) induced hepatotoxicity in mice. Forty mice were divided into four groups (10 mice each); control, MTX, and two sitagliptin groups (pretreated with sitagliptin 10 and 20 mg/kg/day, respectively) for five consecutive days prior to MTX injection. Results showed that MTX induced marked hepatic injury in the form of cloudy swelling, hydropic degeneration, apoptosis and focal necrosis in all hepatic zones. Biochemical analysis revealed significant increase in the serum transaminases, alkaline phosphatase and lactate dehydrogenase in MTX group. Oxidative stress and depressed antioxidant system of the hepatic tissues were evident in MTX group. MTX down-regulated nuclear factor erythroid 2-related factor 2 (Nrf2) expression and reduced its binding capacity. Additionally, MTX increased the activation and the expression of nuclear factor kappa-B (NF-κB) and downstream inflammatory mediators. MTX induced the activation of inducible nitric oxide synthase (iNOS) and increased nitrite/nitrate level. Finally, hepatic cellular apoptosis was clearly obvious in MTX-intoxicated animals using TUNEL staining. Also, there was increase in the immunoexpression of pro-apoptotic protein Bax, increase in Bax and caspase-3 levels and decrease in the level of anti-apoptotic Bcl2 in liver. On the other hand, sitagliptin pretreatment significantly ameliorated all of the above mentioned biochemical, histopathological, immunohistochemical changes induced by MTX. These results provide new evidences that the hepatoprotective effect of sitagliptin is possibly mediated through modulation of Nrf2 and NF-κB signaling pathways with subsequent suppression of inflammatory and apoptotic processes. PMID:28334048

  6. Protective effects of thymoquinone against methotrexate-induced testicular injury.

    PubMed

    Gökçe, Ahmet; Oktar, Suleyman; Koc, Ahmet; Yonden, Zafer

    2011-08-01

    Thymoquinone is the major active component derived from Nigella sativa. Methotrexate is a folic acid antagonist widely used in clinic. Aim of this study was to investigate the possible protective role of thymoquinone on testicular toxicity of methotrexate. Experiments were performed on male C57BL/6 mice (6 weeks old, 20 ± 2 g). The animals were divided into four groups with six mice in each group. Equivalent volumes of saline were injected intraperitoneally (i.p.) in the control group. In the thymoquinone group, mice received thymoquinone i.p. with a dose of 10 mg/kg/day for 4 days. Mice in the methotrexate group received single dose of methotrexate i.p., with a dose of 20 mg/kg. Finally, in the methotrexate plus thymoquinone group, in the first and the following 3 days after methotrexate administration, thymoquinone was injected with a dose of 10 mg/kg/day, i.p. At the end of the experiment, the left testis was quickly removed and divided into two parts for histological examination and biochemical analysis. Methotrexate alone increased total antioxidant capacity and myeloperoxidase activity compared to the controls. Thymoquinone treatment decreased total antioxidant capacity and prevented the increase in the myeloperoxidase activity. Light microscopy showed in mice that receiving methotrexate resulted in interstitial space dilatation, edema, severe disruption of the seminiferous epithelium and reduced diameter of the seminiferous tubules. Administration of thymoquinone reversed histological changes of methotrexate significantly. We suggest that thymoquinone use may decrease the destructive effects of methotrexate on testicular tissue of patients using this agent.

  7. The insecticide buprofezin induces morphological transformation and kinetochore-positive micronuclei in cultured Syrian hamster embryo cells in the absence of detectable DNA damage.

    PubMed

    Herrera, L A; Ostrosky-Wegman, P; Schiffmann, D; Chen, Q Y; Ziegler-Skylakakis, K; Andrae, U

    1993-11-01

    The insecticide buprofezin was examined for its genotoxicity in cultured Syrian hamster embryo cells in order to better understand the mechanisms underlying the genotoxicity of the compound in mammalian cells. Exposure to buprofezin concentrations of 12.5-100 microM did not significantly affect the colony-forming ability of the cells, but did result in increased frequencies of morphologically transformed colonies. Treatment with buprofezin did not cause a detectable induction of DNA repair synthesis, an indicator of DNA damage, but significantly increased the frequency of micronuclei. Immunostaining of the cells with antikinetochore antibody (CREST antibody) showed that essentially all of the buprofezin-induced micronuclei were kinetochore-positive. The results suggest that morphological transformation of Syrian hamster embryo cells by buprofezin results from an interaction of the compound or a metabolite of it with the mitotic apparatus rather than from DNA damage.

  8. Simultaneous Analysis of SEPT9 Promoter Methylation Status, Micronuclei Frequency, and Folate-Related Gene Polymorphisms: The Potential for a Novel Blood-Based Colorectal Cancer Biomarker

    PubMed Central

    Ravegnini, Gloria; Zolezzi Moraga, Juan Manuel; Maffei, Francesca; Musti, Muriel; Zenesini, Corrado; Simeon, Vittorio; Sammarini, Giulia; Festi, Davide; Hrelia, Patrizia; Angelini, Sabrina

    2015-01-01

    One challenge in colorectal cancer (CRC) is identifying novel biomarkers to be introduced in screening programs. The present study investigated the promoter methylation status of the SEPT9 gene in peripheral blood samples of subjects’ positive fecal occult blood test (FOBT). In order to add new insights, we investigated the association between SEPT9 promoter methylation and micronuclei frequency, and polymorphisms in the folate-related pathway genes. SEPT9 promoter methylation, micronuclei frequency, and genotypes were evaluated on 74 individuals’ FOBT positive. Individuals were subjected to a colonoscopy that provided written informed consent for study participation. SEPT9 promoter methylation status was significantly lower in the CRC group than controls (p = 0.0006). In contrast, the CaCo2 cell-line, analyzed as a tissue specific model of colon adenocarcinoma, showed a significantly higher percentage of SEPT9 promoter methylation compared to the CRC group (p < 0.0001). Linear regression analysis showed an inverse correlation between micronuclei frequency and the decrease in the methylation levels of SEPT9 promoter region among CRC patients (β = −0.926, p = 0.0001). With regard to genotype analysis, we showed the involvement of the DHFR polymorphism (rs70991108) in SEPT9 promoter methylation level in CRC patients only. In particular, the presence of at least one 19 bp del allele significantly correlates with decreased SEPT9 promoter methylation, compared to the 19 bp ins/ins genotype (p = 0.007). While remaining aware of the strengths and limitations of the study, this represents the first evidence of a novel approach for the early detection of CRC, using SEPT9 promoter methylation, micronuclei frequency and genotypes, with the potential to improve CRC risk assessment. PMID:26633373

  9. Evaluation of the migration of mutagens/carcinogens from PET bottles into mineral water by Tradescantia/micronuclei test, Comet assay on leukocytes and GC/MS.

    PubMed

    Biscardi, D; Monarca, S; De Fusco, R; Senatore, F; Poli, P; Buschini, A; Rossi, C; Zani, C

    2003-01-20

    This study monitored the release of mutagenic/carcinogenic compounds into mineral water (natural and carbonated) from polyethylene terephthalate (PET) bottles, using a plant mutagenicity test which reveals micronuclei formation in Tradescantia pollen cells (Trad/MCN test), a DNA damage assay (Comet assay) on human leukocytes and gas chromatography/mass spectrometry (GC/MS) for the characterisation of migrants. The water samples were collected at a bottling plant and stored in PET bottles for a period ranging from 1 to 12 months. Every month some samples were randomly collected and lyophilised, the residual powders were extracted with organic solvents and then analysed by GC/MS and tested for DNA damage in human leukocytes, or reconstituted with distilled water to obtain concentrates for the exposure of Tradescantia inflorescences. Micronuclei increase in pollen was found only in natural mineral water stored for 2 months. DNA-damaging activity was found in many of the natural and carbonated water samples. Spring water was negative in the plant micronuclei test and the Comet assay, whereas distributed spring water showed DNA-damaging effects, suggesting a possible introduction of genotoxins through the distribution pipelines. GC/MS analysis showed the presence in mineral water of di(2-ethylhexyl)phthalate, a nongenotoxic hepatocarcinogenic plasticizer, after 9 months of storage in PET bottles. Copyright 2002 Elsevier Science B.V.

  10. Induction of micronuclei and binuclei in blood, gill and liver cells of fishes subchronically exposed to cadmium chloride and copper sulphate.

    PubMed

    Cavas, Tolga; Garanko, Natasha N; Arkhipchuk, Victor V

    2005-04-01

    Common carp (Cyprinus carpio), Prussian carp (Carassius gibelio) and Peppered cory (Corydoras paleatus) were evaluated as target species to perform genotoxicity tests for heavy metals. Fishes were exposed to different doses of cadmium (0.005-0.1 mg/L) and copper (0.01-0.25 mg/L) for 21 days. Hexavalent chromium at a single dose of 5 mg/L was used as a positive control. Frequencies of micronuclei and binuclei were evaluated comparatively in peripheral blood erythrocytes, gill epithelial cells and liver cells. As a result it was observed that, fish species and their tissues showed differential sensitivity to the heavy metal treatment. In general, frequencies of micronucleated and binucleated cells significantly increased following the exposure for 21 days to copper, cadmium and chromium. On the other hand, gill and liver cells showed higher frequencies of micronuclei and binuclei than erythrocytes. Our results indicated the formation of micronuclei and binuclei in fish cells caused by their exposure to cadmium, copper and chromium, thus verifying results obtained earlier on mammals, which indicated that these heavy metals have cytotoxic and genotoxic effects. The suitability of the micronucleus assay in native fish species for the screening of aquatic genotoxicants is highlighted and the importance of target tissue selection in the piscine micronucleus test is emphasized.

  11. Micronuclei and cell proliferation as early biological markers of ortho-phenylphenol-induced changes in the bladder of male F344 rats.

    PubMed

    Balakrishnan, S; Eastmond, D A

    2006-08-01

    ortho-Phenylphenol (OPP) and its sodium salt, sodium ortho-phenylphenate (SOPP), are widely used fungicides and antibacterial agents known to cause tumors in the bladders of male F344 rats. Previous studies in our laboratory have shown that micronuclei and cell proliferation were induced in the bladders of treated rats by a high dose of OPP. In our present studies, we investigated the relationship in dose response between these two biomarkers and previously reported tumor formation in the bladders of male F344 rats. Significant non-linear increases in micronuclei (MN) and BrdU-labeling were seen in the bladder cells of rats treated with the 8000 and 12,500 ppm doses of OPP and at 20,000 ppm SOPP. CREST anti-kinetochore staining showed that the micronuclei originated from both chromosomal loss and breakage. In addition, increases in MN were detected in the bladder but not in the bone marrow, underscoring the value of assessing genotoxicity in the target organ. In summary, these studies clearly show that at high doses, OPP and SOPP are genotoxic to the rat bladder. These results also indicate that micronucleus formation and cell proliferation can detect early OPP-induced changes in the rat bladder and may be useful as biomarkers for bladder carcinogens.

  12. Induction of micronuclei and other nuclear abnormalities in European minnow Phoxinus phoxinus and mollie Poecilia latipinna: an assessment of the fish micronucleus test.

    PubMed

    Ayllon, F; Garcia-Vazquez, E

    2000-05-08

    In this work, we have measured both micronuclei and other nuclear abnormalities in renal erythrocytes from European minnow Phoxinus phoxinus and mollie Poecilia latipinna, with the aim to contribute to the standardisation of the micronucleus test for fish species. Intraperitoneal injections of colchicine (10 mg/kg), cyclophosphamide (40 mg/kg), or mitomycin C (20 mg/kg) for 24 h induced diverse nuclear abnormalities in minnow erythrocytes, therefore nuclear abnormalities should be added to micronuclei as genotoxicity indicators in fish micronucleus tests. The adequacy of administration protocols based on intraperitoneal injections has been evaluated by injecting saline solution to both species: single or double injections have not induced neither micronuclei nor other nuclear abnormalities in any case. Finally, the differential sensitivity of both species to toxic heavy metals was evaluated by exposing individuals of both species to different doses (0.17, 1.7, 2x1.7, and 3.4 mg/kg) of cadmium and mercury for 24 h; we concluded that the mollie is sensitive to both metals whereas the minnow is not sensitive to mercury.

  13. Studies on the alterations in haematological indices, micronuclei induction and pathological marker enzyme activities in Channa punctatus (spotted snakehead) perciformes, channidae exposed to thermal power plant effluent.

    PubMed

    Javed, Mehjbeen; Ahmad, Irshad; Ahmad, Ajaz; Usmani, Nazura; Ahmad, Masood

    2016-01-01

    The present study was conducted to assess the toxicity of thermal power plant effluent containing heavy metals (Fe > Cu > Zn > Mn > Ni > Co > Cr) on haematological indices, micronuclei, lobed nuclei and activity of pathological marker enzymes [alkaline phosphatase (ALP), aspartate transferase (AST), alanine transferase (ALT) and creatine kinase (CK)] in Channa punctatus. Total erythrocyte count (-54.52 %), hemoglobin (-36.98 %), packed cell volume (-36.25 %), mean corpuscular hemoglobin concentration (-1.41 %) and oxygen (O2) carrying capacity (-37.04 %) declined significantly over reference fish, however total leukocyte count (+25.43 %), mean corpuscular hemoglobin (+33.52 %) and mean corpuscular volume (+35.49 %) showed elevation. High frequency of micronuclei (1133.3 %) and lobed nuclei (150 %) were observed in exposed fish which may indicate mutagenesis. Activities of pathological marker enzymes ALP, AST, ALT and CK increased significantly in serum of exposed fish. The ratio of ALT: AST in exposed fish was beyond 1 which indicates manifestation of pathological processes. These biomarkers show that fish have macrocytic hypochromic anemia. Leukocytosis showed general defence response against heavy metal toxicity and marker enzymes showed tissue degeneration. In conclusion, thermal power plant effluent has strong potential to induce micronuclei, tissue pathology, making the fish anemic, weak, stressed and vulnerable to diseases.

  14. Assessment of micronuclei frequency in individuals with a habit of tobacco by means of exfoliated oral buccal cells

    PubMed Central

    Dosi, Tanvi; Gupta, Dhaman; Hazari, Alka; Rajput, Rajan; Chauhan, Prabhav; Rajapuri, Anushri S.

    2016-01-01

    Aims and Objectives: To study the genotoxic effects of tobacco on the exfoliated buccal epithelial cells in patients with oral precancerous lesions (OPLs) and Patients with tobacco habit but without oral precancerous lesion(habit controls) by using micronucleus assay as well as the quantification and detection of the biomarkers in these premalignant lesions which will be helpful in finding those patients who are at higher risk for malignant transformation. Materials and Methods: Forty samples were collected from the right and left side of buccal epithelial cells obtained from 20 individuals, i.e., 10 patients with habit control and 10 patients with OPLs. Statistical analysis was performed by the Statistical Package for the Social Sciences version 21.0 Unpaired t-test was performed to determine the micronucleated cell (MNC) and micronuclei (MN) frequencies in individuals; significance was set at P > 0.05. Results: There was an increase in both the MNC and MN frequency from habit controls to OPLs, indicating that the number of cells with chromosomal damage and extent of chromosomal damage in each cell was high in OPLs. Conclusion: The MN count can be used as a noninvasive tool for early detection, educating patients, screening a large population, and to check the risk for malignancy, which in turn may help in treatment planning. PMID:27652247

  15. Dose rate effect on micronuclei induction in human blood lymphocytes exposed to single pulse and multiple pulses of electrons.

    PubMed

    Acharya, Santhosh; Bhat, N N; Joseph, Praveen; Sanjeev, Ganesh; Sreedevi, B; Narayana, Y

    2011-05-01

    The effects of single pulses and multiple pulses of 7 MV electrons on micronuclei (MN) induction in cytokinesis-blocked human peripheral blood lymphocytes (PBLs) were investigated over a wide range of dose rates per pulse (instantaneous dose rate). PBLs were exposed to graded doses of 2, 3, 4, 6, and 8 Gy of single electron pulses of varying pulse widths at different dose rates per pulse, ranging from 1 × 10(6) Gy s(-1) to 3.2 × 10(8) Gy s(-1). Different dose rates per pulse were achieved by changing the dose per electron pulse by adjusting the beam current and pulse width. MN yields per unit absorbed dose after irradiation with single electron pulses were compared with those of multiple pulses of electrons. A significant decrease in the MN yield with increasing dose rates per pulse was observed, when dose was delivered by a single electron pulse. However, no reduction in the MN yield was observed when dose was delivered by multiple pulses of electrons. The decrease in the yield at high dose rates per pulse suggests possible radical recombination, which leads to decreased biological damage. Cellular response to the presence of very large numbers of chromosomal breaks may also alter the damage.

  16. Dose response of micronuclei induced by combination radiation of α-particles and γ-rays in human lymphoblast cells.

    PubMed

    Ren, Ruiping; He, Mingyuan; Dong, Chen; Xie, Yuexia; Ye, Shuang; Yuan, Dexiao; Shao, Chunlin

    2013-01-01

    Combination radiation is a real situation of both nuclear accident exposure and space radiation environment, but its biological dosimetry is still not established. This study investigated the dose-response of micronuclei (MN) induction in lymphocyte by irradiating HMy2.CIR lymphoblast cells with α-particles, γ-rays, and their combinations. Results showed that the dose-response of MN induced by γ-rays was well-fitted with the linear-quadratic model. But for α-particle irradiation, the MN induction had a biphasic phenomenon containing a low dose hypersensitivity characteristic and its dose response could be well-stimulated with a state vector model where radiation-induced bystander effect (RIBE) was involved. For the combination exposure, the dose response of MN was similar to that of α-irradiation. However, the yield of MN was closely related to the sequence of irradiations. When the cells were irradiated with α-particles at first and then γ-rays, a synergistic effect of MN induction was observed. But when the cells were irradiated with γ-rays followed by α-particles, an antagonistic effect of MN was observed in the low dose range although this combination radiation also yielded a synergistic effect at high doses. When the interval between two irradiations was extended to 4h, a cross-adaptive response against the other irradiation was induced by a low dose of γ-rays but not α-particles.

  17. Incidence of micronuclei in human peripheral blood lymphocytes exposed to modulated and unmodulated 2450 MHz radiofrequency fields.

    PubMed

    Vijayalaxmi; Reddy, Abhishek B; McKenzie, Raymond J; McIntosh, Robert L; Prihoda, Thomas J; Wood, Andrew W

    2013-10-01

    Peripheral blood samples from four healthy volunteers were collected and aliquots were exposed in vitro for 2 h to either (i) modulated (wideband code division multiple access, WCDMA) or unmodulated continuous wave (CW) 2450 MHz radiofrequency (RF) fields at an average specific absorption rate of 10.9 W/kg or (ii) sham-exposed. Aliquots of the same samples that were exposed in vitro to an acute dose of 1.5 Gy ionizing gamma-radiation (GR) were used as positive controls. Half of the aliquots were treated with melatonin (Mel) to investigate if such treatment offers protection to the cells from the genetic damage, if any, induced by RF and GR. The cells in all samples were cultured for 72 h and the lymphocytes were examined to determine the extent of genetic damage assessed from the incidence of micronuclei (MN). The results indicated the following: (i) the incidence of MN was similar in incubator controls, and those exposed to RF/sham and Mel alone; (ii) there were no significant differences between WCDMA and CW RF exposures; (iii) positive control cells exposed to GR alone exhibited significantly increased MN; and (iv) Mel treatment had no effect on cells exposed to RF and sham, while such treatment significantly reduced the frequency of MN in GR-exposed cells.

  18. The effect of 50 Hz electromagnetic fields on the formation of micronuclei in rodent cell lines exposed to gamma radiation.

    PubMed

    Lagroye, I; Poncy, J L

    1997-08-01

    Low frequency electromagnetic fields (EMF) do not produce enough energy to damage DNA, in contrast to ionizing radiations. Any relationship between increased incidence of cancer and EMF must therefore be explained by a promoting effect on cellular transformation by ionizing radiation. The aim of this study was to investigate using the cytokinesis-blocked micronucleus assay a possible amplification of the genotoxic effects of ionizing radiations in cells exposed to combined static and power-frequency electromagnetic fields. Rat tracheal epithelial cell lines were first exposed in vitro to 60Co gamma rays (0, 2 and 6 Gy) and cells were then cultured for 24 h in a homogeneous sinusoidal 50 Hz magnetic field (flux density: 100 microTrms) combined with an artificial geomagnetic-like field created by the use of horizontal and vertical pairs of Helmholtz coils. Control cells were cultured in an adjacent incubator where the background EMF was about 0.1 microTrms. Under our in vitro experimental conditions, EMF appeared to have no significant direct effect on micronucleus induction in rat tracheal cell lines. However, an increased frequency of binucleated cells with micronuclei was observed in cells exposed to 6 Gy of gamma rays and EMF, compared with gamma irradiation alone. This could enhance radiation-induced genomic alterations and increase the probability of neoplastic transformation.

  19. Micronuclei frequency in lymphocytes and antioxidants in the blood of traditional limited-resource farm workers exposed to pesticides.

    PubMed

    Tope, Avinash; Bebe, Frederick N; Panemangalore, Myna

    2006-01-01

    Chronic low-level exposure to synthetic pesticides is implicated in many health conditions that result from the induction of oxidative stress, including cytogenetic damage. The objective of this study was to assess the risk of genotoxicity using micronuclei (MN) formation in lymphocytes and to determine changes in blood antioxidants superoxide dismutase (SOD) in erythrocytes (E) and glutathione (GSH) in E and plasma (PL) in farm workers for six months during a growing season. Blood and urine samples were collected once a month for six months (June to November 2003) from farm workers (n = 15) and urban unexposed controls (n = 10). Lymphocytes from blood were separated by density gradient centrifugation using Histopaque and cultured using the standard technique. There was no significant difference in the cytokinesis blocked proliferation index (CBPI) of lymphocytes between the farm workers and the control group, but there was a 76% increase in average MN frequency in lymphocytes of the farm worker group (P

  20. Modulatory role of GSTM1 null genotype on the frequency of micronuclei in pesticide-exposed agricultural workers.

    PubMed

    Tumer, Tugba Boyunegmez; Savranoglu, Seda; Atmaca, Pelin; Terzioglu, Gulsum; Sen, Alaattin; Arslan, Sevki

    2016-12-01

    In this study, we aimed to investigate the extent of genotoxic risk and the association between null GSTM1/GSTT1 and GSTP1 Ile105Val variants and cellular DNA damage, as measured by micronucleus (MN) assay in a group of agricultural workers from Denizli, Turkey. Peripheral blood samples were collected from 116 subjects, including 58 workers who were occupationally exposed to pesticides and 58 healthy unexposed controls. The MN frequencies of each individual were assessed by cytokinesis-blocked micronuclei assays on lymphocytes. Genotypes for different GST variants were determined using polymerase chain reaction-based methods. A significant 3.4-fold increase in MN frequency was observed in workers compared with the controls (p < 0.001). Among the GST genotypes, only the GSTM1 null genotype was found to be significantly associated with an increased MN frequency in workers (p = 0.01). Individuals with a concomitant null GSTM1/GSTT1 genotype demonstrated a significant (p = 0.01) increase in MN frequency compared with those with functional isozymes in the exposed worker group. The association of the GSTM1 null genotype with higher MN frequency suggests that it may be a modifier of genotoxic risk in individuals exposed to pesticides and may thus be a candidate susceptibility biomarker for human biomonitoring studies. © The Author(s) 2015.

  1. Effects of shielding on the induction of 53BP1 foci and micronuclei after Fe ion exposures

    PubMed Central

    Hu, Wentao; Pei, Hailong; Li, He; Ding, Nan; He, Jinpeng; Wang, Jufang; Furusawa, Yoshiya; Hirayama, Ryoichi; Matsumoto, Yoshitaka; Liu, Cuihua; Li, Yinghui; Kawata, Tetsuya; Zhou, Guangming

    2014-01-01

    High atomic number and high-energy (HZE) particles in deep space are of low abundance but substantially contribute to the biological effects of space radiation. Shielding is so far the most effective way to partially protect astronauts from these highly penetrating particles. However, simulated calculations and measurements have predicted that secondary particles resulting from the shielding of cosmic rays produce a significant fraction of the total dose and dose equivalent. In this study, we investigated the biological effects of secondary radiation with two cell types, and with cells exposed in different phases of the cell cycle, by comparing the biological effects of a 200 MeV/u iron beam with a shielded beam in which the energy of the iron ion beam was decreased from 500 MeV/u to 200 MeV/u with PMMA, polyethylene (PE), or aluminum. We found that beam shielding resulted in increased induction of 53BP1 foci and micronuclei in a cell-type-dependent manner compared with the unshielded 200 MeV/u Fe ion beam. These findings provide experimental proof that the biological effects of secondary particles resulting from the interaction between HZE particles and shielding materials should be considered in shielding design. PMID:23728321

  2. Micronuclei in human peripheral blood lymphocytes exposed to mixed beams of X-rays and alpha particles.

    PubMed

    Staaf, Elina; Brehwens, Karl; Haghdoost, Siamak; Nievaart, Sander; Pachnerova-Brabcova, Katerina; Czub, Joanna; Braziewicz, Janusz; Wojcik, Andrzej

    2012-08-01

    The purpose of this study was to analyse the cytogenetic effect of exposing human peripheral blood lymphocytes (PBL) to a mixed beam of alpha particles and X-rays. Whole blood collected from one donor was exposed to different doses of alpha particles ((241)Am), X-rays and a combination of both. All exposures were carried out at 37 °C. Three independent experiments were performed. Micronuclei (MN) in binucleated PBL were scored as the endpoint. Moreover, the size of MN was measured. The results show that exposure of PBL to a mixed beam of high and low linear energy transfer radiation led to significantly higher than expected frequencies of MN. The measurement of MN size did not reveal any differences between the effect of alpha particles and mixed beam. In conclusion, a combined exposure of PBL to alpha particles and X-rays leads to a synergistic effect as measured by the frequency of MN. From the analysis of MN distributions, we conclude that the increase was due to an impaired repair of X-ray-induced DNA damage.

  3. Indium chloride-induced micronuclei via reactive oxygen species in Chinese hamster lung fibroblast V79 cells.

    PubMed

    Lin, Ruey-Hseng; Yang, Ming-Ling; Li, Yi-Ching; Chang, Hui-Min; Kuan, Yu-Hsiang

    2013-10-01

    We study the cytotoxicity of indium chloride (InCl₃) in Chinese hamster lung fibroblasts, the V79 cells, using MTT assay. The results showed that InCl₃ did not induce significant cytotoxicity at various concentrations tested. In addition, the frequency of micronuclei (MN) was assayed to evaluate the genotoxic effects of InCl₃ in V79 cells. InCl₃ at concentrations ranged 0.1-1 μM significantly increased MN frequency in a concentration-dependent manner. Both catalase and superoxide dismutase at concentrations of 75 and 150 μg/mL significantly inhibited InCl₃-induced MN. Similarly, Germanium oxide (GeO₂) and dimercaprol expressed antigenotoxic effects. From these findings, it is concluded that InCl₃ is a potent genotoxic chemical, which may be mediated partly by inducing oxidative stress. The significance of this study shows that the workers in the semiconductor factories should be cautious in exposing to the hazardous genotoxic InCl₃.

  4. Environmentally Relevant Concentrations of Atrazine and Ametrine Induce Micronuclei Formation and Nuclear Abnormalities in Erythrocytes of Fish.

    PubMed

    Botelho, R G; Monteiro, S H; Christofoletti, C A; Moura-Andrade, G C R; Tornisielo, V L

    2015-11-01

    A rapid and sensitive method using liquid chromatography coupled with mass spectrometry triple quadrupole direct aqueous injection for analysis of atrazine and ametrine herbicides in surface waters was developed. According to the validation method, water samples from six different locations in the Piracicaba River were collected monthly from February 2011 to January 2012 and injected into a liquid chromatographer/dual mass spectrometer without the need for sample extraction. The method was validated and shown to be precise and accurate; limits of detection and quantification were 0.07 and 0.10 µg L(-1) for atrazine and 0.09 and 0.14 µg L(-1) for ametrine. During the sampling period, concentrations of atrazine ranged from 0.11 to 1.92 µg L(-1) and ametrine from 0.25 to 1.44 µg L(-1). After analysis of the herbicides, Danio rerio were exposed a range of concentrations found in the river water to check the induction of micronuclei and nuclear abnormalities (NAs) in erythrocytes. Concentrations of atrazine and ametrine >1.0 and 1.5 µg L(-1), respectively, induced MN formation in D. rerio. Ametrine was shown to be more genotoxic to D. rerio because a greater incidence of NAs was observed compared with atrazine. Therefore, environmentally relevant concentrations of atrazine and ametrine found in the Piracicaba River are dangerous to the aquatic biota.

  5. Effects of shielding on the induction of 53BP1 foci and micronuclei after Fe ion exposures.

    PubMed

    Hu, Wentao; Pei, Hailong; Li, He; Ding, Nan; He, Jinpeng; Wang, Jufang; Furusawa, Yoshiya; Hirayama, Ryoichi; Matsumoto, Yoshitaka; Liu, Cuihua; Li, Yinghui; Kawata, Tetsuya; Zhou, Guangming

    2014-01-01

    High atomic number and high-energy (HZE) particles in deep space are of low abundance but substantially contribute to the biological effects of space radiation. Shielding is so far the most effective way to partially protect astronauts from these highly penetrating particles. However, simulated calculations and measurements have predicted that secondary particles resulting from the shielding of cosmic rays produce a significant fraction of the total dose and dose equivalent. In this study, we investigated the biological effects of secondary radiation with two cell types, and with cells exposed in different phases of the cell cycle, by comparing the biological effects of a 200 MeV/u iron beam with a shielded beam in which the energy of the iron ion beam was decreased from 500 MeV/u to 200 MeV/u with PMMA, polyethylene (PE), or aluminum. We found that beam shielding resulted in increased induction of 53BP1 foci and micronuclei in a cell-type-dependent manner compared with the unshielded 200 MeV/u Fe ion beam. These findings provide experimental proof that the biological effects of secondary particles resulting from the interaction between HZE particles and shielding materials should be considered in shielding design.

  6. Effects of Arbutin on Radiation-Induced Micronuclei in Mice Bone Marrow Cells and Its Definite Dose Reduction Factor.

    PubMed

    Nadi, Saba; Monfared, Ali Shabestani; Mozdarani, Hossein; Mahmodzade, Aziz; Pouramir, Mahdi

    2016-05-01

    Interactions of free radicals from ionizing radiation with DNA can induce DNA damage and lead to mutagenesis and carsinogenesis. With respect to radiation damage to human, it is important to protect humans from side effects induced by ionizing radiation. In the present study, the effects of arbutin were investigated by using the micronucleus test for anti-clastogenic activity, to calculate the ratio of polychromatic erythrocyte to polychromatic erythrocyte plus normochromatic erythrocyte (PCE/PCE+NCE) in order to show cell proliferation activity. Arbutin (50, 100, and 200 mg/kg) was intraperitoneally (ip)administered to NMRI mice two hours before gamma radiation at 2 and 4 gray (Gy). The frequency of micronuclei in 1000 PCEs (MnPCEs) and the ratio of PCE/PCE+NCE were calculated for each sample. Data were statistically evaluated using one-way ANOVA, Tukey HSD test, and t-test. The findings indicated that gamma radiation at 2 and 4 Gy extremely increased the frequencies of MnPCE (P<0.001) while reducing PCE/PCE+NCE (P<0.001) compared to the control group. All three doses of arbutin before irradiation significantly reduced the frequencies of MnPCEs and increased the ratio of PCE/PCE+NCE in mice bone marrow compared to the non-drug-treated irradiated control (P<0.001). All three doses of arbutin had no toxicity effect on bone marrow cells. The calculated dose reduction factor (DRF) showed DRF=1.93 for 2Gy and DRF=2.22 for 4 Gy. Our results demonstrated that arbutin gives significant protection to rat bone against the clastogenic and cytotoxic effects of gamma irradiation.

  7. Effects of Arbutin on Radiation-Induced Micronuclei in Mice Bone Marrow Cells and Its Definite Dose Reduction Factor

    PubMed Central

    Nadi, Saba; Monfared, Ali Shabestani; Mozdarani, Hossein; Mahmodzade, Aziz; Pouramir, Mahdi

    2016-01-01

    Background: Interactions of free radicals from ionizing radiation with DNA can induce DNA damage and lead to mutagenesis and carsinogenesis. With respect to radiation damage to human, it is important to protect humans from side effects induced by ionizing radiation. In the present study, the effects of arbutin were investigated by using the micronucleus test for anti-clastogenic activity, to calculate the ratio of polychromatic erythrocyte to polychromatic erythrocyte plus normochromatic erythrocyte (PCE/PCE+NCE) in order to show cell proliferation activity. Methods: Arbutin (50, 100, and 200 mg/kg) was intraperitoneally (ip)administered to NMRI mice two hours before gamma radiation at 2 and 4 gray (Gy). The frequency of micronuclei in 1000 PCEs (MnPCEs) and the ratio of PCE/PCE+NCE were calculated for each sample. Data were statistically evaluated using one-way ANOVA, Tukey HSD test, and t-test. Results: The findings indicated that gamma radiation at 2 and 4 Gy extremely increased the frequencies of MnPCE (P<0.001) while reducing PCE/PCE+NCE (P<0.001) compared to the control group. All three doses of arbutin before irradiation significantly reduced the frequencies of MnPCEs and increased the ratio of PCE/PCE+NCE in mice bone marrow compared to the non-drug-treated irradiated control (P<0.001). All three doses of arbutin had no toxicity effect on bone marrow cells. The calculated dose reduction factor (DRF) showed DRF=1.93 for 2Gy and DRF=2.22 for 4 Gy. Conclusion: Our results demonstrated that arbutin gives significant protection to rat bone against the clastogenic and cytotoxic effects of gamma irradiation. PMID:27217601

  8. Biologic dosimetry of bone marrow: induction of micronuclei in reticulocytes after exposure to 32P and 90Y.

    PubMed

    Lenarczyk, M; Goddu, S M; Rao, D V; Howell, R W

    2001-01-01

    Bone marrow is the dose-limiting organ in targeted radionuclide therapy. Hence, determination of the absorbed dose to bone marrow from incorporated radionuclides is a critical element in treatment planning. This study investigated the potential of the micronucleus assay in peripheral blood reticulocytes (MnRETs) as an in vivo biologic dosimeter for bone marrow. After intravenous administration of 32P-orthophosphate or 90Y-citrate in Swiss Webster mice, DNA damage induced in bone marrow erythroblastoid cells was measured by subsequent scoring of MnRETs in peripheral blood. The response to exponentially decreasing dose rates was calibrated by irradiating animals with external 137Cs-gamma-rays. The gamma-ray dose rate was decreased exponentially, with the dose-rate decrease half-time corresponding to the effective clearance half-time (Te) of the radioactivity from the femoral bone (Te = 64 h for 90Y-citrate and Te = 255 h for 32P-orthophosphate). The maximum MnRETs frequency occurred on the second and third day after injection of 90Y-citrate and 32P-orthophosphate, respectively. The same pattern was observed for exponentially decreasing dose rates of 137Cs-gamma-rays. For each type of exposure, the maximum MnRETs frequency increased in a dose-dependent manner. Using the calibrated dosimeter, the initial dose rates to the marrow per unit of injected activity were 0.0020 cGy/h/kBq and 0.0026 cGy/h/kBq for 32P-orthophosphate and 90Y-citrate, respectively. Micronuclei in peripheral blood reticulocytes can be used as a noninvasive biologic dosimeter for measuring absorbed dose rate and absorbed dose to bone marrow from incorporated radionuclides.

  9. Protective effect of ferulic acid on gamma-radiation-induced micronuclei, dicentric aberration and lipid peroxidation in human lymphocytes.

    PubMed

    Prasad, N Rajendra; Srinivasan, M; Pugalendi, K V; Menon, Venugopal P

    2006-02-28

    In this study we examined radioprotective effect of ferulic acid (FA) on gamma radiation-induced dicentric aberration and lipid peroxidation with reference to alterations in cellular antioxidant status in cultured lymphocytes. To establish most effective protective support we used three different concentrations of FA (1, 5 and 10 microg/ml) and three different doses of gamma-radiation (1, 2 and 4 Gy). Treatment of lymphocytes with FA alone (at 10 microg/ml) gave no significant change in micronuclei (MN), dicentric aberration (DC), thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) or glutathione peroxidase (GPx) activities when compared with normal lymphocytes; irradiation at 1, 2 and 4 Gy increased the MN and DC frequencies in a dose-dependent manner. Treatment with FA for 30 min before radiation exposure resulted in a significant decline of MN and DC yields as FA concentration increased. Compared to 1 Gy exposure alone, the extent to which FA (1 microg/ml) reduced the MN and DC yields was 75% and 50%, respectively. With 4 Gy irradiation, FA (10 microg/ml) decreased 45% MN and 25% DC frequencies. FA-pretreated lymphocytes (1, 5 and 10 microg/ml) showed progressively decreased TBARS levels after irradiation. Irradiation (1, 2 and 4 Gy) significantly decreased GSH levels, SOD, CAT and GPx activities in a dose-dependent manner. Pretreatment with 10 microg/ml of FA significantly (p<0.05) prevented the decreases in the radiation-induced GSH, SOD, CAT and GPx activities. These findings suggest potential use and benefit of FA as a radioprotector.

  10. Urinary cyclophosphamide excretion and micronuclei frequencies in peripheral lymphocytes and in exfoliated buccal epithelial cells of nurses handling antineoplastics.

    PubMed

    Burgaz, S; Karahalil, B; Bayrak, P; Taşkin, L; Yavuzaslan, F; Bökesoy, I; Anzion, R B; Bos, R P; Platin, N

    1999-02-02

    In this study, urinary cyclophosphamide (CP) excretion rate, as well as micronuclei (MN) in peripheral lymphocytes and in buccal epithelial cells were determined for 26 nurses handling antineoplastics and 14 referents matched for age and sex. In urine samples of 20 out of 25 exposed nurses CP excretion rate was found in a range of 0.02-9.14 microg CP/24 h. Our results of the analyses of CP in urine demonstrates that when the nurses were handling CP (and other antineoplastic drugs) this particular compound was observed in urine. The mean values (+/-SD) of MN frequencies (%) in peripheral lymphocytes from the nurses and controls were 0.61 (+/-0. 32) and 0.28 (+/-0.16), respectively (p<0.01). The mean value (+/-SD) of MN frequency (%) in buccal epithelial cells of nurses was 0.16 (+/-0.19) and also mean MN frequency in buccal epithelial cells for controls was found to be as 0.08 (+/-0.08), (p>0.05). Age, sex and smoking habits have not influenced the parameters analyzed in this study. Handling time of antineoplastics, use of protective equipment and handling frequency of drugs have no effect on urinary and cytogenetic parameters analyzed. No correlation was found between the urinary CP excretion and the cytogenetic findings in nurses. Neither could we find any relationship between two cytogenetic endpoints. Our results have identified the possible genotoxic damage of oncology nurses related to occupational exposure to at least one antineoplastic agent, which is used as a marker for drug handling. As a whole, there is concern that the present handling practices of antineoplastic drugs used in the several hospitals in Ankara will not be sufficient to prevent exposure.

  11. Dioxin-like exposures and effects on estrogenic and androgenic exposures and micronuclei frequency in mother-newborn pairs.

    PubMed

    Pedersen, Marie; Halldorsson, Thorhallur I; Mathiesen, Line; Mose, Tina; Brouwer, Abraham; Hedegaard, Morten; Loft, Steffen; Kleinjans, Jos C S; Besselink, Harrie; Knudsen, Lisbeth E

    2010-05-01

    In utero exposure to environmental dioxin-like, estrogen and androgen compounds can cause adverse health effects. Little is known about potential interactions in vivo between dioxin-like compounds, estrogens and androgens during fetal development in humans. Therefore we explored the potential interactions in vivo between dioxin-like compounds, estrogens, androgens using chemical-activated luciferase expression (CALUX)(R) bioassays in maternal and umbilical cord blood plasma concurrently collected at the time of planned Caesarean section from 98 healthy pregnancies. The dioxin-like activity was also determined after placental transfer of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the ex vivo human placenta perfusion system. Similar dioxin-like activity in maternal and cord blood (37 versus 33pg CALUX(R)-TEQ/g plasma lipids, P>0.05) was detected and it demonstrates transplacental transfer. Increased dioxin-like activity in the perfused placenta tissue after ex vivo TCDD perfusions (from 17 to 280pg CALUX(R)-TEQ/g plasma lipids) suggest that accumulation in the placenta prevents immediate transplacental transfer of TCDD. Androgenic activity were also similar in the paired mother-newborns (0.10 versus 0.18ng CALUX(R)-AEQ/mL plasma), whereas cord blood plasma estrogenic activity was higher than maternal levels (22.6 versus 18.5ng CALUX(R)-EEQ/mL plasma). In cord blood plasma androgenic activity was strongly positively associated with maternal levels (Rs=0.8, P<0.001) whereas dioxin-like and estrogenic activities were modestly associated with maternal levels (Rsmicronuclei frequency, an indicator of genetic instability was significantly associated with dioxin-like activity in cord blood, independently of other recorded factors (Rs=0.4, P<0.003). This study demonstrated interactions in vivo between dioxin-like, estrogenic and androgenic exposures during fetal development of humans.

  12. Does exposure to glyphosate lead to an increase in the micronuclei frequency? A systematic and meta-analytic review.

    PubMed

    Ghisi, Nédia de Castilhos; de Oliveira, Elton Celton; Prioli, Alberto José

    2016-02-01

    Glyphosate-based herbicides are among the most used pesticides worldwide. Reviews on the safety of glyphosate have been conducted by several regulatory agencies and researches centers, many times with contradictory results. This study is a systematic meta-analytical review of experimental studies on the relationship between exposure to the glyphosate (GLY) and its formulations with the formation of micronuclei (MN) to establish a quantitative estimate of the environmental risks. The natural logarithm (ln) of the estimated response ratio was calculated from 81 experiments. A meta-analysis was performed on the complete data set, and individual meta-analyses were conducted after stratification by test system, class of vertebrate, exposure route, gender, endpoints, type of literature, formulation, GLY dose and exposure time. A forest plot showed an overall positive association between GLY exposure and its formulations and MN, corroborated by the cumulative effects size. Different responses were observed on mammalian and non-mammalian. Interesting results was noticed in exposure route where oral administration of GLY presented no significance. Exposure by intraperitoneal injection presented the highest MN formation. Pure GLY caused fewer effects than to commercial mixtures, but both presented mutagenic effects. The studies with males presented significant responses, while studies with females were not significant. The cumulative effects size was not clearly related to GLY dose, and was negatively related to exposure time. It can be attributed to different test systems, exposure routes and protocols analyzed. In conclusion, our results support the hypothesis that exposure to GLY and its formulations increases the frequency of MN formation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Comparative toxicity and micronuclei formation in Tribolium castaneum, Callosobruchus maculatus and Sitophilus oryzae exposed to high doses of gamma radiation.

    PubMed

    Ahmadi, Mehrdad; Mozdarani, Hossein; Abd-Alla, Adly M M

    2015-07-01

    The effects of gamma radiation on mortality and micronucleus formation in Tribolium castaneum Herbst, Callosobruchus maculatus (F.) and Sitophilus oryzae (L.) genital cells were evaluated. Two groups of healthy and active adult insects 1-3 and 8-10 days old were irradiated with various doses (50-200 Gy) gamma ray. Seven days post-irradiation; mortality rates and micronucleus formation were assessed in genital cells of the irradiated insects. The results show that with increasing gamma doses, the mortality rate of each species increased and T. castaneum and S. oryzae showed the low and high sensitivity respectively. It was shown that the micronucleus appearance in the tested insects had correlation with amount and intensity of radiation doses. Moreover our results indicate different levels in the genotoxicity of gamma radiation among the insects' genital cells under study. The frequency of micronuclei in genital cells of 1-3 days old insects exposed to 50 and 200 Gy were 12.6 and 38.8 Mn/1000 cells in T. castaneum, 20.8 and 46.8 Mn/1000 cells in C. maculatus and 16.8 and 57.2 Mn/1000 cells in S. oryzae respectively. A high sensitivity of the genital cells to irradiation exposure was seen in S. oryzae correlated with its high mortality rate compared with the other two species. These results might be indicative of inflicting chromosomal damage expressed as micronucleus in high mortality rates observed in the pest population; an indication of genotoxic effects of radiation on the studied species.

  14. Pharmacological inhibition of Polo Like Kinase 2 (PLK2) does not cause chromosomal damage or result in the formation of micronuclei

    SciTech Connect

    Fitzgerald, Kent; Bergeron, Marcelle; Willits, Christopher; Bowers, Simeon; Aubele, Danielle L.; Goldbach, Erich; Tonn, George; Ness, Daniel; Olaharski, Andrew

    2013-05-15

    Polo Like Kinase 2 (PLK2) phosphorylates α-synuclein and is considered a putative therapeutic target for Parkinson's disease. Several lines of evidence indicate that PLK2 is involved with proper centriole duplication and cell cycle regulation, inhibition of which could impact chromosomal integrity during mitosis. The objectives of the series of experiments presented herein were to assess whether specific inhibition of PLK2 is genotoxic and determine if PLK2 could be considered a tractable pharmacological target for Parkinson's disease. Several selective PLK2 inhibitors, ELN 582175 and ELN 582646, and their inactive enantiomers, ELN 582176 and ELN 582647, did not significantly increase the number of micronuclei in the in vitro micronucleus assay. ELN 582646 was administered to male Sprague Dawley rats in an exploratory 14-day study where flow cytometric analysis of peripheral blood identified a dose-dependent increase in the number of micronucleated reticulocytes. A follow-up investigative study demonstrated that ELN 582646 administered to PLK2 deficient and wildtype mice significantly increased the number of peripheral micronucleated reticulocytes in both genotypes, suggesting that ELN 582646-induced genotoxicity is not through the inhibition of PLK2. Furthermore, significant reduction of retinal phosphorylated α-synuclein levels was observed at three non-genotoxic doses, additional data to suggest that pharmacological inhibition of PLK2 is not the cause of the observed genotoxicity. These data, in aggregate, indicate that PLK2 inhibition is a tractable CNS pharmacological target that does not cause genotoxicity at doses and exposures that engage the target in the sensory retina. - Highlights: • Active and inactive enantiomers test negative in the in vitro micronucleus test. • ELN 582646 significantly increased micronuclei at 100 and 300 mg/kg/day doses. • ELN 582646 significantly increased micronuclei in PLK2 knockout mice. • ELN 582646 decreased

  15. Stress induced by premature chromatin condensation triggers chromosome shattering and chromothripsis at DNA sites still replicating in micronuclei or multinucleate cells when primary nuclei enter mitosis.

    PubMed

    Terzoudi, Georgia I; Karakosta, Maria; Pantelias, Antonio; Hatzi, Vasiliki I; Karachristou, Ioanna; Pantelias, Gabriel

    2015-11-01

    Combination of next-generation DNA sequencing, single nucleotide polymorphism array analyses and bioinformatics has revealed the striking phenomenon of chromothripsis, described as complex genomic rearrangements acquired in a single catastrophic event affecting one or a few chromosomes. Via an unproven mechanism, it is postulated that mechanical stress causes chromosome shattering into small lengths of DNA, which are then randomly reassembled by DNA repair machinery. Chromothripsis is currently examined as an alternative mechanism of oncogenesis, in contrast to the present paradigm that considers a stepwise development of cancer. While evidence for the mechanism(s) underlying chromosome shattering during cancer development remains elusive, a number of hypotheses have been proposed to explain chromothripsis, including ionizing radiation, DNA replication stress, breakage-fusion-bridge cycles, micronuclei formation and premature chromosome compaction. In the present work, we provide experimental evidence on the mechanistic basis of chromothripsis and on how chromosomes can get locally shattered in a single catastrophic event. Considering the dynamic nature of chromatin nucleoprotein complex, capable of rapid unfolding, disassembling, assembling and refolding, we first show that chromatin condensation at repairing or replicating DNA sites induces the mechanical stress needed for chromosome shattering to ensue. Premature chromosome condensation is then used to visualize the dynamic nature of interphase chromatin and demonstrate that such mechanical stress and chromosome shattering can also occur in chromosomes within micronuclei or asynchronous multinucleate cells when primary nuclei enter mitosis. Following an aberrant mitosis, chromosomes could find themselves in the wrong place at the wrong time so that they may undergo massive DNA breakage and rearrangement in a single catastrophic event. Specifically, our results support the hypothesis that premature chromosome

  16. Frequency of micronuclei in the peripheral blood and bone marrow of cancer-prone mice chronically exposed to 2450 MHz radiofrequency radiation.

    PubMed

    Vijayalaxmi; Frei, M R; Dusch, S J; Guel, V; Meltz, M L; Jauchem, J R

    1997-04-01

    C3H/HeJ mice, which are prone to mammary tumors, were exposed for 20 h/day, 7 days/week, over 18 months to continuous-wave 2450 MHz radiofrequency (RF) radiation in circularly polarized wave guides at a whole-body average specific absorption rate of 1.0 W/kg. Sham-exposed mice were used as controls. The positive controls were the sentinel mice treated with mitomycin C during the last 24 h before necropsy. At the end of the 18 months, all mice were necropsied. Peripheral blood and bone marrow smears were examined for the extent of genotoxicity as indicated by the presence of micronuclei in polychromatic erythrocytes (PCEs). The results indicate that the incidence of micronuclei/1,000 PCEs was not significantly different between groups exposed to RF radiation (62 mice) and sham-exposed groups (58 mice), and the mean frequencies were 4.5 +/- 1.23 and 4.0 +/- 1.12 in peripheral blood and 6.1 +/- 1.78 and 5.7 +/- 1.60 in bone marrow, respectively. In contrast, the positive controls (7 mice) showed a significantly elevated incidence of micronuclei/1,000 PCEs in peripheral blood and bone marrow, and the mean frequencies were 50.9 +/- 6.18 and 55.2 +/- 4.65, respectively. When the animals with mammary tumors were considered separately, there were no significant differences in the incidence of micronuclei/1,000 PCEs between the group exposed to RF radiation (12 mice) and the sham-exposed group (8 mice), and the mean frequencies were 4.6 +/- 1.03 and 4.1 +/- 0.89 in peripheral blood and 6.1 +/- 1.76 and 5.5 +/- 1.51 in bone marrow, respectively. Thus there was no evidence for genotoxicity in mice prone to mammary tumors that were exposed chronically to 2450 MHz RF radiation compared with sham-exposed controls.

  17. Common toad Rhinella arenarum (Hensel, 1867) and its importance in assessing environmental health: test of micronuclei and nuclear abnormalities in erythrocytes.

    PubMed

    Pollo, Favio E; Bionda, Clarisa L; Salinas, Zulma A; Salas, Nancy E; Martino, Adolfo L

    2015-09-01

    Anthropogenic activities may generate significant changes in the integrity of aquatic ecosystems, so long-term monitoring of populations that inhabit them is crucial. Counting micronucleated erythrocytes (MN) and erythrocytic nuclear abnormalities (ENA) in peripheral blood is a widely used method for detecting chromosomal damage due to chemical agents in the water. We analyzed MN and ENA frequency in blood obtained from the common toad Rhinella arenarum populations in sites with different degrees of environmental degradation. The results of this study indicate that there is an association between the frequency of micronuclei and nuclear abnormalities and the degree of environmental alteration recorded for the sites studied.

  18. Outdoor air pollution exposures and micronuclei frequencies in lymphocytes from pregnant women and newborns in Crete, Greece (Rhea cohort).

    PubMed

    O'Callaghan-Gordo, Cristina; Fthenou, Eleni; Pedersen, Marie; Espinosa, Ana; Chatzi, Leda; Beelen, Rob; Chalkiadaki, Georgia; Decordier, Ilse; Hoek, Gerard; Merlo, Domenico Franco; Nieuwenhuijsen, Mark; Roumeliotaki, Theano; Vafeiadi, Marina; Vande Loock, Kim; Kleinjans, Jos; Stephanou, Euripides; Kirsch-Volders, Micheline; Kogevinas, Manolis

    2015-11-01

    Micronuclei (MN) are biomarkers of early genetic effects that have been used to investigate the association between environmental exposures and cancer. However, few studies have examined the association between environmental exposures during pregnancy and MN in mothers and newborns. We examined MN frequency in maternal blood and in cord blood, in relation to maternal air pollution exposure, and the potential interaction with maternal vitamin C intake and maternal smoking. We used the cytokinesis-block micronucleus assay to assess MN frequency per 1000 bi-nucleated T-lymphocytes from 181 mothers and 183 newborns born in 2007-2008 in Heraklion (Crete, Greece). The ESCAPE land-use regression methods were used to estimate annual mean exposure to outdoor air pollution [particulate matter (PM), black carbon, nitrogen dioxide (NO2) and nitrogen oxides (NOx)] at maternal home addresses. Food frequency questionnaires were used to estimate maternal dietary vitamin C intake during pregnancy. Smoking habits were self-reported using questionnaires which were checked by measuring maternal urinary cotinine levels. Exposure to PM2.5 was associated with increased MN frequencies in pregnant women [rate ratio [RR (95%CI)] per 5 µg/m(3)=1.53 (1.02, 2.29)]. This increase was considerably higher among women who did not fulfill the recommended vitamin C dietary allowances [RR=9.35 (2.77, 31.61); n=20]. Exposure to PM2.5-10, PM10, NO2 and NOx were also associated with a higher incidence of MN frequencies in smoker women (n=56). No associations were found for newborns. We found an association between air pollution, particularly PM2.5, and MN frequency in mothers but not in newborns. This association was more pronounced among women with a lower dietary intake of vitamin C during pregnancy and among women who smoked during pregnancy. While results are clear in mothers, the association between maternal carcinogenic exposures during pregnancy and biomarkers of early biologic effect in the

  19. Energy-dependent RBE of neutrons to induce micronuclei in root-tip cells of Allium cepa onion irradiated as dry dormant seeds and seedlings.

    PubMed

    Zhang, Wenyi; Fujikawa, Kazuo; Endo, Satoru; Ishikawa, Masayori; Ohtaki, Megu; Ikeda, Hideo; Hoshi, Masaharu

    2003-06-01

    The relative biological effectiveness (RBE) of various energy neutrons produced from a Schenkel-type accelerator at the Research Institute for Radiation Biology and Medicine, Hiroshima University (HIRRAC), compared with 60Co gamma-ray radiation was determined. The neutron radiations and gamma-ray radiation produced good linear changes in the frequency of micronuclei induced in the root-tip cells of Allium cepa onion irradiated as dry dormant seeds (seed assay) and seedlings (seedling assay) with varying radiation doses. Therefore the RBE for radiation-induced micronuclei can be calculated as the ratio of the slopes of the fitted linear dose response for the neutron radiations and the 60Co gamma-ray radiation. The RBE values by seed assay and seedling assay decreased to 174 +/- 7, from 216 +/- 9, and to 31.4 +/- 1.0, from 45.3 +/- 1.3 (one standard error), respectively, when neutron energies increased to 1.0 MeV, from 0.2 MeV, in the present study. Furthermore, the ratio of the micronucleus induction rates of seed assay to seedling assay by gamma-ray radiation was much lower than that by neutron radiations.

  20. Evaluation of the effects of ellagic acid (EA) on 7,12-dimethylbenz(α) anthracene (DMBA) induced micronuclei in mammalian cells in vitro and in vivo.

    PubMed

    Grossi, Maria Rosaria; Berni, Andrea; Pepe, Gaetano; Filippi, Silvia; Meschini, Roberta; Papeschi, Cristiano; Natarajan, Adayapalam T; Palitti, Fabrizio

    2014-01-13

    We evaluated the protective effects of EA, a promising dietary constituent against degenerative diseases, on the clastogenic action of the model carcinogen DMBA in vitro on human hepatoma cells (HepG2) and in vivo on bone marrow of mice, using the frequencies of induced micronuclei as the end point. Pre-, post- and simultaneous treatments with EA and the carcinogen were carried out in vitro. Simultaneous treatment with EA caused a statistically significant increase of DMBA induced MN, suggesting a direct interaction between the two agents. No significant reduction in DMBA induced MN was found by pre- or post treatment with EA. Similar effects were observed in the toxicity assay. In in vivo experiments, EA pre-treatment did not affect the frequencies of MN in PCEs of bone marrow induced by DMBA. A good correlation was found between in vitro and in vivo experiments. Our results did not reveal any clear indication on the efficacy of EA on the induction of micronuclei by DMBA. EA by itself did not show any harmful effects.

  1. A Case-Control Study of Oral Epithelial Proliferative Markers among Sudanese Toombak Dippers Using Micronuclei Assay, Argyrophilic Nucleolar Organizer Region, Papanicolaou and Crystal Violet Methods

    PubMed Central

    Anass, M. Abbas; G. Ahmed, Hussain

    2013-01-01

    The use of Toombak has been reported to play a major role in the etiology of oral cancer in Sudan. The cellular proliferative activity on the oral epithelium of 210 Toombak dippers was assessed by applying the micronuclei frequency, mean argyrophilic nucleolar organizer region (AgNOR) counts, Papanicolaou method, and 1% crystal violet stain. Participants were divided into 3 groups: 200 were apparently healthy individuals, 100 were Toombak users (cases), 100 were non-tobacco users (control) and 10 were patients with oral squamous cell carcinomas. Cytological atypia was identified among 4 (4%). Toombak users and was not found among the control group (P<0.04). The micronuclei frequencies were higher in Toombak users (1.026) than in the control group (0.356) (P<0.0001). The mean AgNOR counts in Toombak users (2.423) were higher than control group (1.303) (P<0.0001). Neither Toombak users nor control group showed mitotic figures in 1% crystal violet method. The results of this research showed that Toombak dipping is a high risk factor for increase in the cellular proliferation in the oral mucosa. The cytological proliferative marker methods used are useful for screening Toombak users. PMID:24179643

  2. Bilirubin UDP-Glucuronosyltransferase 1A1 (UGT1A1) Gene Promoter Polymorphisms and HPRT, Glycophorin A, and Micronuclei Mutant Frequencies in Human Blood

    SciTech Connect

    Grant, D; Hall, I J; Eastmond, D; Jones, I M; Bell, D A

    2004-10-06

    A dinucleotide repeat polymorphism (5-, 6-, 7-, or 8-TA units) has been identified within the promoter region of UDP-glucuronosyltransferase 1A1 gene (UGT1A1). The 7-TA repeat allele has been associated with elevated serum bilirubin levels that cause a mild hyperbilirubinemia (Gilbert's syndrome). Studies suggest that promoter transcriptional activity of UGT1A1 is inversely related to the number of TA repeats and that unconjugated bilirubin concentration increases directly with the number of TA repeat elements. Because bilirubin is a known antioxidant, we hypothesized that UGT1A1 repeats associated with higher bilirubin may be protective against oxidative damage. We examined the effect of UGT1A1 genotype on somatic mutant frequency in the hypoxanthine-guanine phosphoribosyl-transferase (HPRT) gene in human lymphocytes and the glycophorin A (GPA) gene of red blood cells (both N0, NN mutants), and the frequency of lymphocyte micronuclei (both kinetochore (K) positive or micronuclei K negative) in 101 healthy smoking and nonsmoking individuals. As hypothesized, genotypes containing 7-TA and 8-TA displayed marginally lower GPA{_}NN mutant frequency relative to 5/5, 5/6, 6/6 genotypes (p<0.05). In contrast, our analysis showed that lower expressing UGT1A1 alleles (7-TA and 8-TA) were associated with modestly increased HPRT mutation frequency (p<0.05) while the same low expression genotypes were not significantly associated with micronuclei frequencies (K-positive or K-negative) when compared to high expression genotypes (5-TA and 6-TA). We found weak evidence that UGT1A1 genotypes containing 7-TA and 8-TA were associated with increased GPA{_}N0 mutant frequency relative to 5/5, 5/6, 6/6 genotypes (p<0.05). These data suggest that UGT1A1 genotype may modulate somatic mutation of some types, in some cell lineages, by a mechanism not involving bilirubin antioxidant activity. More detailed studies examining UGT1A1 promoter variation, oxidant/antioxidant balance and genetic

  3. Induction of micronuclei and nuclear abnormalities by cyclophosphamide and colchicine in Xenotoca melanosoma (Pisces, Goodeidae) from Lake La Alberca in Michoacan, Mexico.

    PubMed

    Zavala-Aguirre, Jose Luis; Torres-Bugarin, Olivia; Buelna-Osben, Hector Rene; Flores-Kehn, Lola Paulina; Ramos-Ibarra, Maria Luisa; Zuniga-Gonzalez, Guillermo; Ogura, Tetsuya

    2010-01-01

    This study is a follow-up of previous research in which we described the frequency of spontaneous micronucleated erythrocytes (MNE) in the Goodeid Xenotocoa melanosoma collected from Lake La Alberca, located in the state of Michoacan, Mexico. In the present work, we measured micronuclei (MN) and nuclear abnormalities (NA) in erythrocytes of peripheral blood. Bioassays taken at 24 or 96 hours in either the cyclophosfamide (CP) or colchicine (COL) showed a significant increase in MN and BC (P values ranging from 0.0499 to 0.0036) compared with information from wild organisms collected over 3 years. Concentrationdependent and time-dependent responses support the proposal of using endemic Xenotoca melanosoma as a bioindicator of genotoxicity and cytotoxicity with a high transcendence for the health of the entire ecosystem and evaluation of the Lerma-Chapala watershed.

  4. Frequencies of micronuclei (MNi), nucleoplasmic bridges (NPBs), and nuclear buds (NBUDs) in farmers exposed to pesticides in Çanakkale, Turkey.

    PubMed

    Coskun, Mahmut; Coskun, Munevver; Cayir, Akin; Ozdemir, Ozturk

    2011-01-01

    This study aimed to determine the incidence of micronuclei (MNi), nucleoplasmic bridges (NPBs), and nuclear buds (NBUDs) in peripheral blood lymphocytes due to direct exposure to pesticides among 46 farmers in Çanakkale, Turkey. 48 non-exposed individuals living in the same socioeconomic conditions were chosen as control. In addition, a cytokinesis-block proliferation index (CBPI) was calculated. MNi and NBUDs frequencies were significantly higher among the farmers (p < 0.05). Although the NPB frequency of the farmers was higher than the controls, there was no statistical difference. Multiple linear regression analysis showed that apart from gender, no significant effects of various confounding factors were observed. Regarding CBPI, data obtained for the controls were higher than that of the farmers; however, there was no statistically significant difference.

  5. Double minute chromosomes in acute myeloid leukemia, myelodysplastic syndromes, and chronic myelomonocytic leukemia are associated with micronuclei, MYC or MLL amplification, and complex karyotype.

    PubMed

    Huh, Yang O; Tang, Guilin; Talwalkar, Sameer S; Khoury, Joseph D; Ohanian, Maro; Bueso-Ramos, Carlos E; Abruzzo, Lynne V

    2016-01-01

    Double minute chromosomes (dmin) are small, paired chromatin bodies that lack a centromere and represent a form of extrachromosomal gene amplification. Dmin are rare in myeloid neoplasms and are generally associated with a poor prognosis. Most studies of dmin in myeloid neoplasms are case reports or small series. In the current study, we present the clinicopathologic and cytogenetic features of 22 patients with myeloid neoplasms harboring dmin. These neoplasms included acute myeloid leukemia (AML) (n = 18), myelodysplastic syndrome (MDS) (n = 3), and chronic myelomonocytic leukemia (CMML) (n = 1). The AML cases consisted of AML with myelodysplasia-related changes (n = 13) and therapy-related AML (n = 5). Dmin were detected in initial pre-therapy samples in 14 patients with AML or CMML; they were acquired during the disease course in 8 patients who had AML or MDS. The presence of dmin was associated with micronuclei (18/18; 100%), complex karyotype (17/22; 77.3%), and amplification of MYC (12/16; 75%) or MLL (4/16; 25%). Immunohistochemical staining for MYC performed on bone marrow core biopsy or clot sections revealed increased MYC protein in all 19 cases tested. Except for one patient, most patients failed to respond to risk-adapted chemotherapies. At last follow up, all patients had died of disease after a median of 5 months following dmin detection. In conclusion, dmin in myeloid neoplasms commonly harbor MYC or MLL gene amplification and manifest as micronuclei within leukemic blasts. Dmin are often associated with myelodysplasia or therapy-related disease, and complex karyotypes.

  6. Micronuclei in red blood cells of the newt Pleurodeles waltl after treatment with benzo(a)pyrene: dependence on dose, length of exposure, posttreatment time, and uptake of the drug

    SciTech Connect

    Grinfeld, S.; Jaylet, A.; Siboulet, R.; Deparis, P.; Chouroulinkov, I.

    1986-01-01

    Aquatic larvae of the newt Pleurodeles waltl were exposed to different concentrations of benzo(a)pyrene (BaP) for various lengths of time. Frequencies of micronuclei in circulating erythrocytes were determined at different times after termination of the treatment. The incidence of micronuclei in larvae kept for 8 days in BaP-containing water displayed a marked increase with dose up to 0.075 ppm and a more gradual one with higher doses, reaching 158 per 1000 at 0.75 ppm. The lowest dose at which a significant increase could be discerned was 0.01 ppm. Short periods of exposure, less than 2 days, did not result in a marked increase in micronuclei. Uptake and release was studied with tritiated BaP. Larvae concentrated BaP rapidly, attaining maximal levels after 12 hr. Radioactive larvae placed in regularly renewed noncontaminated water lost 99% of the label after 100 hr. It is concluded that pleurodele larvae are a promising model for the detection of genotoxic activity in the aquatic environment.

  7. Micronuclei in mouse skin cells following in vivo exposure to benzo(a)pyrene, 7,12-dimethylbenz(a)anthracene, chrysene, pyrene and urethane

    SciTech Connect

    Shuilin He ); Baker, R. )

    1991-01-01

    Detection of micronuclei (MN) in skin cells from HRA/Skh hairless mice treated with chemical or physical agents may prove informative in qualitative and quantitative studies of skin carcinogenesis. MN induction and cell survival were estimated in cytokinesis-blocked keratinocytes, cultured for 4 days in vitro, after a single topical dose of various organic compounds. Treatment with 7,12-dimethylbenz(a)anthracene (DMBA) resulted in maximal MN induction in cells removed from skin 12-24 hr after topical administration. Even in cells removed only 1 hr after DMBA treatment, a significant increase in MN was evident. However, to allow sufficient time for metabolic activation, a sampling time of 24 hr was adopted for all test substances. Dose-dependent increases in MN were observed with DMBA, benzo(a)pyrene, chrysene, and urethane. Increased numbers of micronucleated cells were detected at the lowest doses administered in the present study. Although reduced cell recovery occurred following exposure of mice to acetone, pyrene, and other chemicals, there was no evidence that cytotoxicity contributed to MN scored in keratinocytes. Moreover, the probable noncarcinogen, pyrene, failed to induce MN at doses from 2.5 {mu}g to 2.5 mg/mouse. These results show that it is possible to assess chemical exposure in skin by measuring cell survival and skin genotoxicity by measuring MN induction in cultured keratinocytes.

  8. The effect of dietary estimates calculated using food frequency questionnaires on micronuclei formation in European pregnant women: a NewGeneris study.

    PubMed

    Vande Loock, Kim; Botsivali, Maria; Zangogianni, Marina; Anderson, Diana; Baumgartner, Adolph; Fthenou, Eleni; Chatzi, Leda; Marcos, Ricard; Agramunt, Sylvia; Namork, Ellen; Granum, Berit; Knudsen, Lisbeth E; Nielssen, Jeanette K S; Meltzer, Helle Margrete; Haugen, Margaretha; Kyrtopoulos, Soterios A; Decordier, Ilse; Plas, Gina; Roelants, Mathieu; Merlo, Franco; Kleinjans, Jos; Kogevinas, Manolis; Kirsch-Volders, Micheline

    2014-11-01

    The use of biomarkers of early genetic effects, predictive for cancer, such as micronuclei (MN) in lymphocytes, may help to investigate the association between diet and cancer. We hypothesised that the presence of mutagens in the diet may increase MN formation. A 'pooled' standardised analysis was performed by applying the same experimental protocol for the cytokinesis block micronucleus assay in 625 young healthy women after delivery from five European study populations (Greece, Denmark, UK, Spain and Norway). We assessed MN frequencies in mono- and binucleated T-lymphocytes (MNMONO and MNBN) and the cytokinesis blocked proliferation index using a semi-automated image analysis system. Food frequency questionnaires (FFQs) were used to estimate intake of fatty acids and a broad range of immunotoxic and genotoxic/carcinogenic compounds through the diet. Pooled difference based on delivery type revealed higher MNMONO frequencies in caesarean than in vaginal delivery (P = 0.002). Statistical analysis showed a decrease in MNMONO frequencies with increasing calculated omega-6 PUFA concentrations and a decrease in MNBN frequencies with increasing calculated omega-3 PUFA concentrations. The expected toxic compounds estimated by FFQs were not associated with MN formation in mothers after delivery. In pregnant women, an omega-3 and -6 rich diet estimated by FFQ is associated with lower MN formation during pregnancy and delivery. © The Author 2014. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  9. Modulatory of effect of fresh Amaranthus caudatus and Amaranthus hybridus aqueous leaf extracts on detoxify enzymes and micronuclei formation after exposure to sodium arsenite

    PubMed Central

    Adewale, Adetutu; Olorunju, Awe Emmanuel

    2013-01-01

    Vegetables are the cheapest and most available sources of important proteins, minerals, vitamins, and essential amino protein. These vegetables are commonly used in Africa for the treatment of illness. This study evaluated the protective effects of Amaranthus caudatus and A. hybridus against sodium arsenite-induced toxicity in rats. The effects of sodium arsenite and/or the plant extracts were assessed using bone marrow micronucleus assay and by measuring the activities of tumour maker enzymes such as gamma glutamyl transferase (GGT) and alkaline phosphatase (ALP) in white albino Wister rats. The study showed that sodium arsenite significantly (P < 0.05) induced the formation of micronucleated polychromatic erythrocytes and the activities of ALP and GGT when compared with control. The levels of white blood cell, hemoglobin, and lymphocyte count were altered in sodium arsenite fed rats and were reverted back to near normal levels in rats pretreated with the plant extracts. A. caudatus and A. hybridus showed significant role in protecting the detoxifying enzymes; also, A. caudatus has a more protective effect on reducing the micronuclei formation when compared with A. hybridus. This study suggests that A. caudatus and A. hybridus possess anticarcinogenic effect. PMID:24174825

  10. Chromosome nondisjunction during bipolar mitoses of binucleated intermediates promote aneuploidy formation along with multipolar mitoses rather than chromosome loss in micronuclei induced by asbestos.

    PubMed

    Zhang, Tianwei; Lv, Lei; Huang, Yun; Ren, Xiaohui; Shi, Qinghua

    2017-02-14

    Asbestos is a well-known occupational carcinogen that can cause aneuploidy during the early stages of neoplastic development. To explore the origins of asbestos-induced aneuploidy, we performed long-term live-cell imaging followed by fluorescence in situ hybridization of chromosomes 8 and 12 in human bronchial epithelial (HBEC) and mesothelial (MeT5A) cells. We demonstrate that asbestos induces aneuploidy via binucleated intermediates resulting from cytokinesis failure. On the one hand, asbestos increases chromosome nondisjunction during bipolar divisions of binucleated intermediates and produces near-tetraploidy. On the other hand, asbestos increases multipolar divisions of binucleated intermediates to produce aneuploidy. Surprisingly, chromosomes in asbestos-induced micronucleated cells are not truly lost by the cells, and do not contribute to aneuploid cell formation in either cell type. These results clarify the cellular source of asbestos-induced aneuploidy. In particular, they show the asbestos-induced disruption of bipolar chromosomal segregation in tetraploid cells, thereby demonstrating the causality between binucleated intermediates and aneuploidy evolution, rather than chromosome loss in micronuclei.

  11. Erythrocyte micronuclei in winter flounder (Pseudopleuronectes americanus): results of field surveys during 1980-1988 from Virginia to Nova Scotia and in Long Island Sound.

    PubMed

    Hughes, J B; Hebert, A T

    1991-05-01

    Erythrocyte micronuclei (MN) frequencies of 280 winter flounder (Pseudopleuronectes americanus) from Chesapeake Bay to the southern Scotian Shelf including Long Island Sound were measured. The MN data were combined with data previously reported for 224 flounder and the combined data sets were analyzed. Incidences of MN were elevated sixfold in flounder from the New York Bight Apex as compared to frequencies for fish from the inshore Gulf of Maine and Block Island Sound, and twice those found in Georges Bank and Long Island Sound flounder. Inshore New Jersey fish had higher MN frequencies than those from inshore Gulf Of Maine and Block Island Sound. The occurrence of MN in flounder from inshore Virginia was higher than in flounder from inshore Gulf of Maine and Block Island Sound. The large subset of stations from Long Island Sound indicated higher frequencies of MN in flounder from Hempstead and Shoreham as compared to most other sites in the Sound. There was no significant difference in the frequency of MN between males and females, but males had significantly more MN than sexually immature flounder. Flounder over the entire sampling area had increased levels of MN during the fall months of the year. This is probably influenced by the maternal cycle of gonadal maturation.

  12. Aberrations of chromosome 19 in asbestos-associated lung cancer and in asbestos-induced micronuclei of bronchial epithelial cells in vitro.

    PubMed

    Ruosaari, Salla T; Nymark, Penny E H; Aavikko, Mervi M; Kettunen, Eeva; Knuutila, Sakari; Hollmén, Jaakko; Norppa, Hannu; Anttila, Sisko L

    2008-05-01

    Exposure to asbestos is known to induce lung cancer, and our previous studies have suggested that specific chromosomal regions, such as 19p13, are preferentially aberrant in lung tumours of asbestos-exposed patients. Here, we further examined the association between the 19p region and exposure to asbestos using array comparative genomic hybridization and fluorescence in situ hybridization (FISH) in lung tumours and FISH characterization of asbestos-induced micronuclei (MN) in human bronchial epithelial BEAS 2B cells in vitro. We detected an increased number of 19p losses in the tumours of asbestos-exposed patients in comparison with tumours from non-exposed subjects with similar distribution of tumour histology in both groups (13/33; 39% versus 3/25; 12%, P = 0.04). In BEAS 2B cells, a 48 h exposure to crocidolite asbestos (2.0 microg/cm(2)) was found to induce centromere-negative MN-harbouring chromosomal fragments. Furthermore, an increased frequency of rare MN containing a 19p fragment was observed after the crocidolite treatment in comparison with untreated controls (6/6000 versus 1/10 000, P = 0.01). The results suggest that 19p has significance in asbestos-associated carcinogenesis and that asbestos may be capable of inducing specific chromosome aberrations.

  13. Micronuclei in Cord Blood Lymphocytes and Associations with Biomarkers of Exposure to Carcinogens and Hormonally Active Factors, Gene Polymorphisms, and Gene Expression: The NewGeneris Cohort

    PubMed Central

    Merlo, Domenico Franco; Agramunt, Silvia; Anna, Lívia; Besselink, Harrie; Botsivali, Maria; Brady, Nigel J.; Ceppi, Marcello; Chatzi, Leda; Chen, Bowang; Decordier, Ilse; Farmer, Peter B.; Fleming, Sarah; Fontana, Vincenzo; Försti, Asta; Fthenou, Eleni; Gallo, Fabio; Georgiadis, Panagiotis; Gmuender, Hans; Godschalk, Roger W.; Granum, Berit; Hardie, Laura J.; Hemminki, Kari; Hochstenbach, Kevin; Knudsen, Lisbeth E.; Kogevinas, Manolis; Kovács, Katalin; Kyrtopoulos, Soterios A.; Løvik, Martinus; Nielsen, Jeanette K; Nygaard, Unni Cecilie; Pedersen, Marie; Rydberg, Per; Schoket, Bernadette; Segerbäck, Dan; Singh, Rajinder; Sunyer, Jordi; Törnqvist, Margareta; van Loveren, Henk; van Schooten, Frederik J.; Vande Loock, Kim; von Stedingk, Hans; Wright, John; Kirsch-Volders, Micheline; van Delft, Joost H.M.

    2013-01-01

    Background: Leukemia incidence has increased in recent decades among European children, suggesting that early-life environmental exposures play an important role in disease development. Objectives: We investigated the hypothesis that childhood susceptibility may increase as a result of in utero exposure to carcinogens and hormonally acting factors. Using cord blood samples from the NewGeneris cohort, we examined associations between a range of biomarkers of carcinogen exposure and hormonally acting factors with micronuclei (MN) frequency as a proxy measure of cancer risk. Associations with gene expression and genotype were also explored. Methods: DNA and protein adducts, gene expression profiles, circulating hormonally acting factors, and GWAS (genome-wide association study) data were investigated in relation to genomic damage measured by MN frequency in lymphocytes from 623 newborns enrolled between 2006 and 2010 across Europe. Results: Malondialdehyde DNA adducts (M1dG) were associated with increased MN frequency in binucleated lymphocytes (MNBN), and exposure to androgenic, estrogenic, and dioxin-like compounds was associated with MN frequency in mononucleated lymphocytes (MNMONO), although no monotonic exposure–outcome relationship was observed. Lower frequencies of MNBN were associated with a 1-unit increase expression of PDCD11, LATS2, TRIM13, CD28, SMC1A, IL7R, and NIPBL genes. Gene expression was significantly higher in association with the highest versus lowest category of bulky and M1dG–DNA adducts for five and six genes, respectively. Gene expression levels were significantly lower for 11 genes in association with the highest versus lowest category of plasma AR CALUX® (chemically activated luciferase expression for androgens) (8 genes), ERα CALUX® (for estrogens) (2 genes), and DR CALUX® (for dioxins). Several SNPs (single-nucleotide polymorphisms) on chromosome 11 near FOLH1 significantly modified associations between androgen activity and MNBN

  14. Genotoxicity evaluation of nanomaterials: dna damage, micronuclei, and 8-hydroxy-2-deoxyguanosine induced by magnetic doped CdSe quantum dots in male mice.

    PubMed

    Khalil, W K B; Girgis, E; Emam, A N; Mohamed, M B; Rao, K V

    2011-05-16

    Quantum dots (QDs) are a novel class of inorganic fluorophores which are gaining widespread recognition as a result of their exceptional photophysical properties and their applications as a biomarker and in molecular biomedical imaging. The aim of this study was to evaluate the in vivo genotoxicity in mice exposed to CdSe quantum dots of average size 5.0 ± 0.2 nm and CdSe doped with 1% cobalt ions of similar size. The quantum dots are surface modified using mercaptoacetic acid (MAA) in order to be biocompatible and water-soluble. The MAA-QDs were given to the mice orally at doses of 500, 1000, and 2000 mg/kg by weight of MAA-QDs. Bone marrow and liver samples were collected after two and seven days of treatment. The results indicated that after two days of treatment, the high dose of doped MAA-QDs was significantly able to induce DNA damage, formation of micronuclei (MNs), and generation of DNA adduct (8-hydroxy-2-deoxyguanosine, 8-OHdG). However, increasing DNA damage and the frequency of MNs formation as well as the generation of DNA adducts were observed with both the undoped MAA-QDs (2000 mg/kg) and doped MAA-QDs (1000 and 2000 mg/kg) after seven days of treatment. The results of our study indicate that exposure to high doses of pure MAA-QDs or MAA-QDs doped with cobalt has the potential to cause indirect in vivo genetic damage, which may be attributed to free radical-induced oxidative stress in mice.

  15. Increased incidence of micronuclei assessed with the micronucleus assay and the fluorescence in situ hybridization (FISH) technique in peripheral blood lymphocytes of nurses exposed to nitrous oxide.

    PubMed

    Lewińska, D; Stepnik, M; Krajewski, W; Arkusz, J; Stańczyk, M; Wrońska-Nofer, T

    2005-03-07

    It has been postulated that exposure to nitrous oxide and halogenated anaesthetics is associated with various adverse health effects such as neurological and reproductive abnormalities or impairment of hepatic functions. In spite of the quite well known genotoxic effects of exposure to nitrous oxide in vivo, the mechanisms of these effects are still not clear. The aim of this study was to assess the frequency of micronuclei and to identify the type of chromosomal damage (clastogenic or aneugenic) in peripheral blood lymphocytes of operating-room nurses exposed to nitrous oxide. The study group comprised 46 women working at departments where the concentration of nitrous oxide ranged from 14 to 2308 mg/m3. The control population was composed of 28 women employed in the same hospitals but in non-surgical departments. The clastogenic/aneugenic effect of nitrous oxide was evaluated in lymphocytes using the standard micronucleus (MN) assay in combination with the fluorescence in situ hybridization (FISH) technique with pancentromeric probes. The results show a significant increase of the MN frequency in lymphocytes of exposed nurses compared with the control group (4.36+/-2.23 versus 9.02+/-4.67). The multiple regression analysis revealed a statistically significant relationship (p=0.0009) between MN frequency and exposure status, indicating that the level of exposure was the main factor affecting chromosomal damage. As assessed by FISH analysis, the overall frequencies of centromere-positive MN in the control and exposed groups were 43 and 49%, respectively. The increase observed in the exposed group may suggest a slight, statistically insignificant pro-aneugenic effect of exposure to nitrous oxide.

  16. Effect of vitamin-antioxidant micronutrients on the frequency of spontaneous and in vitro gamma-ray-induced micronuclei in lymphocytes of donors: the age factor.

    PubMed

    Gaziev, A I; Sologub, G R; Fomenko, L A; Zaichkina, S I; Kosyakova, N I; Bradbury, R J

    1996-03-01

    The effect of prolonged consumption of a vitamin-antioxidant mixture (VAM) on the frequency of spontaneous and in vitro gamma-radiation-induced micronuclei (MN) in peripheral blood lymphocytes in donors of various ages was investigated. Three groups of donors were recruited: (i) 56-83 years old (35 subjects), (ii) 23-30 years old (13 subjects), and (iii) 63-82 years old (12 subjects). Blood was sampled every 4 months for one year in all donors of the three groups. After the first sampling of blood, the donors of groups (i) and (ii) took VAM containing the vitamins A, C, E, as well as beta-carotene, folic acid, and rutin daily for 4 months. After the second blood sampling, the intake of VAM was terminated. The third blood sample was taken 4 months after termination of VAM intake. A part of the blood was exposed to gamma-radiation and the frequency of spontaneous and induced MN in lymphocytes was assayed. The analyses showed that the frequency of spontaneous and in vitro gamma-ray-induced MN in aged donors was significantly higher than that in young donors. No seasonal variations in MN frequency were observed in human lymphocytes during one year. Aged donors showed a statistically significant decrease in spontaneous MN in lymphocytes after a 4 month period of consumption of VAM. The intake of VAM by both aged and young donors promoted a decrease in MN induced lymphocytes in vitro by gamma-radiation. The results of our observations enable the suggestion that consumption of VAM favours a decrease in the chromosome damage produced by endogenous and exogenous factors in human lymphocytes.

  17. Exposure to genotoxic agents, host factors, and lifestyle influence the number of centromeric signals in micronuclei: a pooled re-analysis.

    PubMed

    Iarmarcovai, G; Bonassi, S; Sari-Minodier, I; Baciuchka-Palmaro, M; Botta, A; Orsière, T

    2007-02-03

    We pooled data from three biomonitoring studies using the cytokinesis-block micronucleus assay in peripheral blood lymphocytes in combination with fluorescence in situ hybridization. Centromere-positive micronuclei (C+MN) were classified in two groups: those containing one centromere (C1+MN) and those with two or more (Cx+MN). The three studies evaluated untreated cancer patients, welders, and pathologists/anatomists exposed to formaldehyde. The total number of subjects included in the pooled re-analysis was 113. A higher frequency of C+MN was observed in cancer patients and exposed workers, who showed significant differences from controls in all studies. C1+MN were particularly increased in the group of pathologists/anatomists, who showed a 3.29 times higher frequency than controls (95% CI: 2.04-5.30). A borderline increase in Cx+MN was observed in welders when compared to the corresponding control group (FR: 1.31; 95% CI: 0.99-1.74). An evident effect of gender was found, with significantly increased frequencies of all endpoints measuring aneuploidy in females (C+MN, C1+MN, and Cx+MN). Alcohol consumption had a significant effect on total MN frequency and particularly on C+MN and C1+MN. In conclusion, scoring the number of centromeric signals in the micronucleus assay provides additional information about the mechanism of action of various genotoxic agents, and the role of confounding factors may be more specifically accounted for. Indeed, C+MN could be efficiently used in biomonitoring studies as an independent biomarker of exposure and early biological effect. The use of centromeric signals allows the identification of two further endpoints, representing two alternative pathways of chromosome loss, i.e., impaired chromosome migration, leading to increased C1+MN frequency, and centrosome amplification, possibly leading to Cx+MN with two or more centromeric signals.

  18. Micronuclei related to anti-B[a]PDE-DNA adduct in peripheral blood lymphocytes of heavily polycyclic aromatic hydrocarbon-exposed nonsmoking coke-oven workers and controls.

    PubMed

    Pavanello, Sofia; Kapka, Lucyna; Siwinska, Ewa; Mielzyñska, Danuta; Bolognesi, Claudia; Clonfero, Erminio

    2008-10-01

    Micronuclei (MN) frequency associated to biologically effective dose of polycyclic aromatic hydrocarbons [PAH; anti-benzo[a]pyrene diolepoxide (B[a]PDE)-DNA] within the same subjects' peripheral blood lymphocytes (PBL) was evaluated. Study subjects were nonsmoking male Polish coke-oven workers (n=49) and matched controls (n=45) verified for PAH exposure by urinary 1-pyrenol. We found that coke-oven workers, heavily exposed to PAHs (80% workers exceeded the urinary 1-pyrenol biological exposure index value), presented significantly higher MN frequency in PBLs than controls (P<0.01). Substantial difference was also found for adduct levels in PBLs (P<0.01). Increase in MN levels was significantly related to anti-B[a]PDE-DNA formation, key adduct of the ultimate carcinogenic metabolite of B[a]P (n=94; r=0.47; P<0.001). The dose-response relationship was improved when subjects with adduct levels above the 3rd tertile (>or=4.35 adducts/10(8) nucleotides) were excluded (n=61; r=0.69; P<0.001). Saturation of adduct/MN formation at high levels may disturb the underlying relationship. Linear multiple regression analysis, without subjects of 3rd tertile adduct level (n=61), revealed that adduct formation (t=4.61; P<0.001), but not 1-pyrenol, was the significant determinant in increasing MN. In conclusion, the increase in MN frequency is mainly related to the specific anti-B[a]PDE-DNA formation within PBLs of the same subject. Our results substantiate, with the use of an early indicator of biological effect as well, that workers are at higher cancer risk than controls.

  19. Human CYP2E1-dependent and human sulfotransferase 1A1-modulated induction of micronuclei by benzene and its hydroxylated metabolites in Chinese hamster V79-derived cells.

    PubMed

    Jiang, Hao; Lai, Yanmei; Hu, Keqi; Wei, Qinzhi; Liu, Yungang

    2014-12-01

    Benzene is a ubiquitous environmental pollutant and a confirmed human carcinogen, which requires metabolic activation, primarily by CYP2E1, for most of its biological actions. Chromosome damages in benzene-exposed workers and rodents have been observed, and in their urine sulfo- and glucuronide-conjugates of phenol and hydroquinone were present. Yet, direct evidence for human CYP2E1-activated mutagenicity of benzene and the exact significance of phase II metabolism for inactivating benzene metabolites are still missing. In the present study, benzene and its oxidized metabolites (phenol, hydroquinone, catechol, 1,2,4-trihydroxybenzene and 1,4-benzoquinone) were investigated for induction of micronuclei in a V79-derived cell line genetically engineered for expression of both human CYP2E1 and human sulfotransferase (SULT) 1A1 (indicated by active micronuclei induction by 1-hydroxymethylpyrene). The results demonstrated concentration-dependent induction of micronuclei by benzene and phenol, though with lower potency or efficacy than the other metabolites. Inhibition of CYP2E1 by 1-aminobenzotriazole did not change the effect of benzoquinone, but completely abolished that of benzene and phenol, and attenuated that of the other compounds. Moreover, inhibition of SULT1A1 by pentachlorophenol potentiated the effects of benzene, hydroquinone, catechol and trihydroxybenzene. Ascorbic acid, a reducing and free radical-scavenging agent, significantly lowered the effects of hydroquinone, catechol, trihydroxybenzene as well as N-nitrosodimethylamine (a known CYP2E1-dependent promutagen), with that of benzoquinone unaffected. These results suggest that in addition to activating benzene and phenol, human CYP2E1 may further convert hydroquinone, catechol and trihydroxybenzene to more genotoxic metabolites, and sulfo-conjugation of the multi-hydroxylated metabolites of benzene by human SULT1A1 may represent an important detoxifying pathway.

  20. Comparative investigations of sodium arsenite, arsenic trioxide and cadmium sulphate in combination with gamma-radiation on apoptosis, micronuclei induction and DNA damage in a human lymphoblastoid cell line.

    PubMed

    Hornhardt, Sabine; Gomolka, Maria; Walsh, Linda; Jung, Thomas

    2006-08-30

    In the field of radiation protection the combined exposure to radiation and other toxic agents is recognised as an important research area. To elucidate the basic mechanisms of simultaneous exposure, the interaction of the carcinogens and environmental toxicants cadmium and two arsenic compounds, arsenite and arsenic trioxide, in combination with gamma-radiation in human lymphoblastoid cells (TK6) were investigated. Gamma-radiation induced significant genotoxic effects such as micronuclei formation, DNA damage and apoptosis, whereas arsenic and cadmium had no significant effect on these indicators of cellular damage at non-toxic concentrations. However, in combination with gamma-radiation arsenic trioxide induced a more than additive apoptotic rate compared to the sum of the single effects. Here, the level of apoptotic cells was increased, in a dose-dependent way, up to two-fold compared to the irradiated control cells. Arsenite did not induce a significant additive effect at any of the concentrations or radiation doses tested. On the other hand, arsenic trioxide was less effective than arsenite in the induction of DNA protein cross-links. These data indicate that the two arsenic compounds interact through different pathways in the cell. Cadmium sulphate, like arsenite, had no significant effect on apoptosis in combination with gamma-radiation at low concentrations and, at high concentrations, even reduced the radiation-induced apoptosis. An additive effect on micronuclei induction was observed with 1muM cadmium sulphate with an increase of up to 80% compared to the irradiated control cells. Toxic concentrations of cadmium and arsenic trioxide seemed to reduce micronuclei induction. The results presented here indicate that relatively low concentrations of arsenic and cadmium, close to those occuring in nature, may interfere with radiation effects. Differences in action of the two arsenic compounds were identified.

  1. Microcystin-LR, a protein phosphatase inhibitor, induces alterations in mitotic chromatin and microtubule organization leading to the formation of micronuclei in Vicia faba

    PubMed Central

    Beyer, Dániel; Tándor, Ildikó; Kónya, Zoltán; Bátori, Róbert; Roszik, Janos; Vereb, György; Erdődi, Ferenc; Vasas, Gábor; M-Hamvas, Márta; Jambrovics, Károly; Máthé, Csaba

    2012-01-01

    Background and Aims Microcystin-LR (MCY-LR) is a cyanobacterial toxin, a specific inhibitor of type 1 and 2A protein phosphatases (PP1 and PP2A) with significant impact on aquatic ecosystems. It has the potential to alter regulation of the plant cell cycle. The aim of this study was improved understanding of the mitotic alterations induced by cyanotoxin in Vicia faba, a model organism for plant cell biology studies. Methods Vicia faba seedlings were treated over the long and short term with MCY-LR purified in our laboratory. Short-term treatments were performed on root meristems synchronized with hydroxylurea. Sections of lateral root tips were labelled for chromatin, phosphorylated histone H3 and β-tubulin via histochemical and immunohistochemical methods. Mitotic activity and the occurrence of mitotic alterations were detected and analysed by fluorescence microscopy. The phosphorylation state of histone H3 was studied by Western blotting. Key Results Long-term MCY-LR exposure of lateral root tip meristems increased the percentage of either early or late mitosis in a concentration-dependent manner. We observed hypercondensed chromosomes and altered sister chromatid segregation (lagging chromosomes) leading to the formation of micronuclei, accompanied by the formation of disrupted, multipolar and monopolar spindles, disrupted phragmoplasts and the hyperphosphorylation of histone H3 at Ser10. Short-term MCY-LR treatment of synchronized cells showed that PP1 and PP2A inhibition delayed the onset of anaphase at 1 µg mL−1 MCY-LR, accelerated cell cycle at 10 µg mL−1 MCY-LR and induced the formation of lagging chromosomes. In this case mitotic microtubule alterations were not detected, but histone H3 was hyperphosphorylated. Conclusions MCY-LR delayed metaphase–anaphase transition. Consequently, it induced aberrant chromatid segregation and micronucleus formation that could be associated with both H3 hyperphosphorylation and altered microtubule organization

  2. A combined analysis of XRCC1, XRCC3, GSTM1 and GSTT1 polymorphisms and centromere content of micronuclei in welders.

    PubMed

    Iarmarcovai, G; Sari-Minodier, I; Orsière, T; De Méo, M; Gallice, P; Bideau, C; Iniesta, D; Pompili, J; Bergé-Lefranc, J L; Botta, A

    2006-03-01

    The aims of the present study were to assess clastogenic and aneugenic properties of welding fumes using fluorescent in situ hybridization (FISH) with a human pancentromeric DNA probe. The involvement of genetic polymorphisms in DNA repair genes (p.Arg399Gln of XRCC1 and p.Thr241Met of XRCC3) and in detoxification genes (GSTM1 and GSTT1) on the centromere content of micronuclei (MN) was also evaluated. This study included 27 male welders working without any collective protection device and a control group (n = 30). The welders showed significantly higher levels of chromosome/genome damage compared to the controls. The frequencies of MN and centromere-positive MN (C+MN) per 1,000 binucleated cells were significantly higher in the exposed group than in the control group (7.1 per thousand +/- 3.7 versus 4.9 per thousand +/- 1.8; P = 0.012 and 3.5 per thousand +/- 1.8 versus 2.4 per thousand +/- 1.2; P = 0.018, respectively, Mann-Whitney U-test). The centromere-negative MN (C-MN) frequency was higher in the exposed subjects than in the controls (3.6 per thousand +/- 3.4 versus 2.5 per thousand +/- 1.4), but the Mann-Whitney U-test did not yield a significant result. In the total population, the GSTM1 and GSTT1 polymorphisms significantly affected the frequencies of C-MN and C+MN defined by FISH. GSTM1 positive subjects showed an increased C-MN frequency and GSTT1 null subjects showed an elevated C+MN frequency. When GSTM1 and GSTT1 genotypes were included in multiple regression analysis, the effect of the occupational exposure could better be demonstrated; both C+MN and C-MN were significantly increased in the welders. Our results suggest that the combined analysis of genetic polymorphisms and centromeres in MN may improve the sensitivity of the micronucleus assay in detecting genotoxic effects.

  3. Microcystin-LR, a protein phosphatase inhibitor, induces alterations in mitotic chromatin and microtubule organization leading to the formation of micronuclei in Vicia faba.

    PubMed

    Beyer, Dániel; Tándor, Ildikó; Kónya, Zoltán; Bátori, Róbert; Roszik, Janos; Vereb, György; Erdodi, Ferenc; Vasas, Gábor; M-Hamvas, Márta; Jambrovics, Károly; Máthé, Csaba

    2012-09-01

    Microcystin-LR (MCY-LR) is a cyanobacterial toxin, a specific inhibitor of type 1 and 2A protein phosphatases (PP1 and PP2A) with significant impact on aquatic ecosystems. It has the potential to alter regulation of the plant cell cycle. The aim of this study was improved understanding of the mitotic alterations induced by cyanotoxin in Vicia faba, a model organism for plant cell biology studies. Vicia faba seedlings were treated over the long and short term with MCY-LR purified in our laboratory. Short-term treatments were performed on root meristems synchronized with hydroxylurea. Sections of lateral root tips were labelled for chromatin, phosphorylated histone H3 and β-tubulin via histochemical and immunohistochemical methods. Mitotic activity and the occurrence of mitotic alterations were detected and analysed by fluorescence microscopy. The phosphorylation state of histone H3 was studied by Western blotting. Long-term MCY-LR exposure of lateral root tip meristems increased the percentage of either early or late mitosis in a concentration-dependent manner. We observed hypercondensed chromosomes and altered sister chromatid segregation (lagging chromosomes) leading to the formation of micronuclei, accompanied by the formation of disrupted, multipolar and monopolar spindles, disrupted phragmoplasts and the hyperphosphorylation of histone H3 at Ser10. Short-term MCY-LR treatment of synchronized cells showed that PP1 and PP2A inhibition delayed the onset of anaphase at 1 µg mL(-1) MCY-LR, accelerated cell cycle at 10 µg mL(-1) MCY-LR and induced the formation of lagging chromosomes. In this case mitotic microtubule alterations were not detected, but histone H3 was hyperphosphorylated. MCY-LR delayed metaphase-anaphase transition. Consequently, it induced aberrant chromatid segregation and micronucleus formation that could be associated with both H3 hyperphosphorylation and altered microtubule organization. However, these two phenomena seemed to be independent

  4. Risk of environmental genotoxicity in the Baltic Sea over the period of 2009-2011 assessed by micronuclei frequencies in blood erythrocytes of flounder (Platichthys flesus), herring (Clupea harengus) and eelpout (Zoarces viviparus).

    PubMed

    Baršienė, Janina; Rybakovas, Aleksandras; Lang, Thomas; Grygiel, Wlodzimierz; Andreikėnaitė, Laura; Michailovas, Aleksandras

    2012-06-01

    Environmental genotoxicity was investigated at 82 locations encompassing different regions of the Baltic Sea. Micronuclei (MN) analysis was performed in erythrocytes of 1892 specimens of flounder Platichthys flesus, herring Clupea harengus and eelpout Zoarces viviparus, three of the most common native fish species of the Baltic Sea collected in 2009-2011. MN background levels in fish were determined using data obtained in 2001-2011 from 107 Baltic sites. Extremely high genotoxicity risk zones were found for flounder at 11 stations out of 16 in 2009 and 33 stations of 41 in 2010-2011, for herring, at 5 of 18 stations in 2009 and 20 of 43 stations in 2010-2011, in eelpout only at one out of 29 stations. The sampling stations were restricted mainly to the southern and eastern Baltic Sea offshore zones and in most of them, MN frequencies in flounder and herring significantly exceeded the reference and background levels of micronuclei. This is a first attempt to evaluate the background MN responses, as well as low, high and extremely high genotoxicity risk levels for native fish species.

  5. FISH analysis of 1cen-1q12 breakage, chromosome 1 numerical abnormalities and centromeric content of micronuclei in buccal cells from thyroid cancer and hyperthyroidism patients treated with radioactive iodine.

    PubMed

    Ramírez, M J; Surrallés, J; Galofré, P; Creus, A; Marcos, R

    1999-01-01

    One of the health consequences of the Chernobyl nuclear power plant accident was a radioactive iodine-related increase in the incidence of thyroid cancer in exposed children. This radioisotope is used in the treatment of thyroid cancer and hyperthyroidism patients providing a convenient opportunity to study cytogenetic damage induced by known doses of radioactive iodine in treated patients. We used pancentromeric FISH on micronuclei and chromosome 1 tandem labelling FISH to monitor overall chromosome breakage and loss, 1q12 breakage and decondensation and chromosome 1 numerical abnormalities in buccal cells from 31 radioactive iodine-exposed hyperthyroidism and thyroid cancer patients. The overall outcome of the study, with 250,000 buccal cells analysed, is that there was no radioactive iodine-related increase in the frequency of micronuclei, 1q12 breakage, 1q12 decondensation or chromosome 1 numerical abnormalities. In addition, neither age nor gender, health status nor radioactive iodine dose modulated the frequency of the above cytogenetic end points. Although several uncertainties of these emerging molecular cytogenetic methodologies will require further experimentation, we conclude that, at the reported exposure levels, radioactive iodine did not induce detectable chromosome damage in buccal cells from treated patients.

  6. Productivity

    Treesearch

    Thomas R. Fox; Ray R. Hicks

    2004-01-01

    The South is blessed with abundant and diverse forest resources. Today, forests cover approximately 215 million acres in the South, which represents 29 percent of the forest land in the United States (Conner and Hartsell 2002). Maintaining the productivity of these forests is essential to the economic, environmental, and social well being of the South and the Nation....

  7. Protective effects of carvacrol against methotrexate-induced testicular toxicity in rats

    PubMed Central

    Daggulli, Mansur; Dede, Onur; Utangac, Mehmet Mazhar; Bodakci, Mehmet Nuri; Hatipoglu, Namık Kemal; Penbegul, Necmettin; Sancaktutar, Ahmet Ali; Bozkurt, Yaşar; Türkçü, Gül; Yüksel, Hatice

    2014-01-01

    To investigate the effect of carvacrol (CAR) on methotrexate (MTX)-induced testis damage in rats. Twenty-four male rats were equally divided into three groups: group I control treatment; group II MTX-treated; group III MTX + CAR-treated. A single dose of CAR was administered intraperitoneally to group III on the first day of the experiment and a single dose of MTX was administered intraperitoneally to groups II and III on the second day of the experiment. The total duration of the experiment was 8 days. Blood samples and testis tissue were obtained from each animal for the measurement of malondialdehyde (MDA), Total oxidant status (TOS), Total Antioxidant Status (TAS), and Oxidative stress index (OSI). Light microscopy was used to complete the histopathological examination of testis specimens from each animal. Analysis of serum and testis sampled revealed that MDA, TOS and OSI levels were significantly greater in the group receiving MTX alone relative to the control treated animals while the TAS level was significantly reduced in the MTX group when compared with the control group. The administration of CAR was associated with significantly decreased MDA, TOS, and OSI levels and increased TAS levels relative to the rats treated with MTX alone. All of these quantitative values demonstrate that CAR alleviates deleterious effects of MTX on testicular tissue. Use of antioxidants such as CAR may protect germ cells against oxidative stress and apoptosis when used in combination with MTX. PMID:25664063

  8. Carvacrol and Pomegranate Extract in Treating Methotrexate-Induced Lung Oxidative Injury in Rats

    PubMed Central

    Şen, Hadice Selimoğlu; Şen, Velat; Bozkurt, Mehtap; Türkçü, Gül; Güzel, Abdulmenap; Sezgi, Cengizhan; Abakay, Özlem; Kaplan, Ibrahim

    2014-01-01

    Background This study was designed to evaluate the effects of carvacrol (CRV) and pomegranate extract (PE) on methotrexate (MTX)-induced lung injury in rats. Material/Methods A total of 32 male rats were subdivided into 4 groups: control (group I), MTX treated (group II), MTX+CRV treated (group III), and MTX+PE treated (group IV). A single dose of 73 mg/kg CRV was administered intraperitoneally to rats in group III on Day 1 of the investigation. To group IV, a dose of 225 mg/kg of PE was administered via orogastric gavage once daily over 7 days. A single dose of 20 mg/kg of MTX was given intraperitoneally to groups II, III, and IV on Day 2. The total duration of experiment was 8 days. Malondialdehyde (MDA), total oxidant status (TOS), total antioxidant capacity (TAC), and oxidative stress index (OSI) were measured from rat lung tissues and cardiac blood samples. Results Serum and lung specimen analyses demonstrated that MDA, TOS, and OSI levels were significantly greater in group II relative to controls. Conversely, the TAC level was significantly reduced in group II when compared to the control group. Pre-administering either CRV or PE was associated with decreased MDA, TOS, and OSI levels and increased TAC levels compared to rats treated with MTX alone. Histopathological examination revealed that lung injury was less severe in group III and IV relative to group II. Conclusions MTX treatment results in rat lung oxidative damage that is partially counteracted by pretreatment with either CRV or PE. PMID:25326861

  9. Altered systemic bioavailability and organ distribution of azathioprine in methotrexate-induced intestinal mucositis in rats

    PubMed Central

    Karbelkar, Sadaf A.; Majumdar, Anuradha S.

    2016-01-01

    Objective: Intestinal mucositis is a significant problem haunting clinicians for decades. One of the major reasons for its occurrence is high-dose chemotherapy. The study is aimed at investigating effect of intestinal mucositis on pharmacokinetics, organ distribution, and bioavailability of azathioprine (AZA) (6-mercaptopurine). Materials and Methods: Intestinal mucositis was induced with methotrexate (MTX) (2.5 mg/kg). The oral absorption of AZA and 6-mercaptopurine (metabolite) levels were determined in control and MTX-treated rats: ex vivo (noneverted sac technique) and in vivo (pharmacokinetics and organ-distribution) using high-performance liquid chromatography. Immunohistochemistry was conducted to evaluate peptide transporter expression on luminal membrane of small intestine. Results: Intestinal permeation of AZA into systemic circulation of rats was lower after MTX administration, widely found in intestinal segments of mucositis-induced rats leading to decline in systemic bioavailability of AZA. Immunohistochemistry findings indicated diminution of peptide transporter expression representing hampered absorption of drugs absorbed via this transporter. Conclusion: Study outcome has thrown light on altered fate of AZA when administered to individuals with mucositis which suggests modified drug therapy. These findings can further be investigated in different drug classes which might be administered concomitantly in mucositis and study outcome can be further confirmed in mucositis patients in clinical practice also. PMID:27298491

  10. Folate antagonist, methotrexate induces neuronal differentiation of human embryonic stem cells transplanted into nude mouse retina.

    PubMed

    Hara, Akira; Taguchi, Ayako; Aoki, Hitomi; Hatano, Yuichiro; Niwa, Masayuki; Yamada, Yasuhiro; Kunisada, Takahiro

    2010-06-25

    Transplanted embryonic stem (ES) cells can be integrated into the retinas of adult mice as well-differentiated neuroretinal cells. However, the transplanted ES cells also have a tumorigenic activity as they have the ability for multipotent differentiation to various types of tissues. In the present study, human ES (hES) cells were transplanted into adult nude mouse retinas by intravitreal injections 20 h after intravitreal N-methyl-D-aspartate (NMDA) administration. After the transplantation of hES cells, the folate antagonist, methotrexate (MTX) was administrated in order to control the differentiation of the transplanted hES cells. Neuronal differentiation and teratogenic potential of hES cells were examined immunohistochemically 5 weeks after transplantation. The proliferative activity of transplanted cells was determined by both the mitotic index and the Ki-67 proliferative index. Disappearance of Oct-4-positive hES cells showing undifferentiated morphology was observed after intraperitoneal MTX treatment daily, for 15 days. Decreased mitotic and Ki-67 proliferative indices, and increased neuronal differentiation were detected in the surviving hES cells after the MTX treatment. These results suggest two important effects of intraperitoneal MTX treatment for hES cells transplanted into nude mouse retina: (1) MTX treatment following transplantation induces neuronal differentiation, and (2) MTX decreases proliferative activity and tumorigenic potential.

  11. Hepatoprotective effect of mulberry (Morus nigra) leaves extract against methotrexate induced hepatotoxicity in male albino rat.

    PubMed

    Tag, Hend M

    2015-07-25

    Drug-induced liver injury is a major health problem that challenges not only health care professionals but also the pharmaceutical industry and drug regulatory agencies. The possible hepatoprotective effect of the administration of mulberry ethanolic extract (MUL) leaves against hepatotoxic effect of the anti-rheumatic drug, methotrexate (MTX) was evaluated in this study both vivo (using animal models) and in vitro (human hepatoma HepG2 cells). In the in-vivo study, 20 male albino rats were equally assigned into four groups; control group received distilled water orally; MUL treated-group received 500 mg/kg/day of MUL extract; MTX treated-group was injected with a single dose of 20 mg/kg MTX intraperitoneally on the 4th day; MUL-MTX treated-group received the previously mentioned doses of MUL and MTX (both control and MUL treated groups were administered a single dose of a physiological saline i.p.). At the end of the experimental period (14 days) activities of alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) as well as total serum protein (TP) and albumin (ALB) levels were evaluated to assess liver function. A marked reduction in the viability of HepG2 cells was observed after 48 h with IC50 equal to 14.5 μg/mL of MUL administration. Treating the animals with MUL in combination with MTX mitigated liver injury, causing a significant reduction in activities of AST, ALT, ALP and LDH as compared to the MTX-group. The liver architecture revealed more or less normal appearance with the combined treatment when compared with MTX treatment alone. This study recommends that the co-administration of MUL with MTX that may have therapeutic benefits against MTX-hepato-cytotoxicity.

  12. Methotrexate induces DNA damage and inhibits homologous recombination repair in choriocarcinoma cells

    PubMed Central

    Xie, Lisha; Zhao, Tiancen; Cai, Jing; Su, You; Wang, Zehua; Dong, Weihong

    2016-01-01

    Objective The objective of this study was to investigate the mechanism of sensitivity to methotrexate (MTX) in human choriocarcinoma cells regarding DNA damage response. Methods Two choriocarcinoma cancer cell lines, JAR and JEG-3, were utilized in this study. An MTX-sensitive osteosarcoma cell line MG63, an MTX-resistant epithelial ovarian cancer cell line A2780 and an MTX-resistant cervical adenocarcinoma cell line Hela served as controls. Cell viability assay was carried out to assess MTX sensitivity of cell lines. MTX-induced DNA damage was evaluated by comet assay. Quantitative reverse transcription polymerase chain reaction was used to detect the mRNA levels of BRCA1, BRCA2, RAD51 and RAD52. The protein levels of γH2AX, RAD 51 and p53 were analyzed by Western blot. Results Remarkable DNA strand breaks were observed in MTX-sensitive cell lines (JAR, JEG-3 and MG63) but not in MTX-resistant cancer cells (A2780 and Hela) after 48 h of MTX treatment. Only in the choriocarcinoma cells, the expression of homologous recombination (HR) repair gene RAD51 was dramatically suppressed by MTX in a dose- and time-dependent manner, accompanied with the increase in p53. Conclusion The MTX-induced DNA strand breaks accompanied by deficiencies in HR repair may contribute to the hypersensitivity to chemotherapy in choriocarcinoma. PMID:27895503

  13. Genetic and metabolic determinants of methotrexate-induced mucositis in pediatric acute lymphoblastic leukemia.

    PubMed

    den Hoed, M A H; Lopez-Lopez, E; te Winkel, M L; Tissing, W; de Rooij, J D E; Gutierrez-Camino, A; Garcia-Orad, A; den Boer, E; Pieters, R; Pluijm, S M F; de Jonge, R; van den Heuvel-Eibrink, M M

    2015-06-01

    Methotrexate (MTX) is an effective and toxic chemotherapeutic drug in the treatment of pediatric acute lymphoblastic leukemia(ALL). In this prospective study, we aimed to identify metabolic and genetic determinants of MTX toxicity. One hundred and thirty-four Dutch pediatric ALL patients were treated with four high infusions MTX (HD-MTX: 5 g m(-2)) every other week according to the DCOG-ALL-10 protocol. Mucositis (National Cancer Institute grade ⩾ 3) was the most frequent occurring toxicity during the HD-MTX phase (20%) and occurred especially after the first MTX course. Mucositis was not associated with plasma MTX, plasma folate or plasma homocysteine levels. Patients with mucositis had higher erythrocyte folate levels at the start of protocol M than patients without mucositis (median 1.4 vs 1.2 μmol l(-1), P<0.008), this could reflect an increased MTX uptake in mucosal cells of patients with mucositis. From 17 single-nucleotide polymorphisms in the MTX pathway, only patients with the wild-type variant of rs7317112 SNP in the ABCC4 gene had more mucositis (AA (39%) vs AG/GG (15%), P=0.016). We found no evidence that erythrocyte folate levels mediate in the association between the rs7317112 and mucositis.

  14. Beneficial effects of Chrysin against Methotrexate-induced hepatotoxicity via attenuation of oxidative stress and apoptosis.

    PubMed

    Ali, Nemat; Rashid, Summya; Nafees, Sana; Hasan, Syed Kazim; Sultana, Sarwat

    2014-01-01

    Methotrexate (MTX), a folic acid antagonist, an effective chemotherapeutic agent is used in the treatment of a wide range of tumors and autoimmune diseases. Moreover, hepatotoxicity limits its clinical use. Several studies have already confirmed that the oxidative stress plays a major role in the pathogenesis of MTX-induced damage in the various organs especially in liver. The aim of this study was to determine the protective effect of Chrysin against MTX-induced hepatic oxidative stress and apoptosis in rats. In the present study, efficacy of Chrysin was investigated against hepatotoxicity caused by MTX in terms of biochemical investigations of antioxidant enzymes, apoptosis, and histopathological alteration in rat liver. In the MTX-treated group there was a significant increase in alanine transaminase, aspartate aminotransferase, lactate dehydrogenase activity and malondialdehyde content as well as decreased glutathione peroxidase, glutathione reductase, superoxide dismutase, catalase activities and reduced glutathione content were also observed compared to the control group as a marker of oxidative stress. Histopathological alterations and apoptosis through the immunopositive staining of p53, cleaved caspases-3 and Bcl-2-associated X protein in rat liver were observed. Pretreatment of Chrysin at both doses prevents the hepatotoxicity by ameliorating oxidative stress, histopathological alterations, and apoptosis and thus our results suggest that Chrysin has a protective effect against hepatotoxicity induced by MTX and it may, therefore, improve the therapeutic index of MTX if co-administration is done.

  15. Resveratrol ameliorates methotrexate-induced hepatotoxicity in rats via inhibition of lipid peroxidation.

    PubMed

    Dalaklioglu, S; Genc, G E; Aksoy, N H; Akcit, F; Gumuslu, S

    2013-06-01

    Hepatotoxicity is one of the major complications of methotrexate (MTX) therapy. This study was carried out to evaluate the possible protective effect of resveratrol (trans-3,5,4'-trihydroxystilbene, RVT) against MTX-induced hepatotoxicity. Rats were randomly divided into four groups as control, MTX treated (7 mg/kg/day, intraperitoneally (i.p.), once daily for 3 consecutive days), MTX + RVT treated (20 mg/kg/day, i.p.), and RVT treated. First dose of RVT was administrated 3 days before the MTX injection and continued for 3 days. Histopathology of liver was evaluated by light microscopy. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) were used as biochemical markers of MTX-induced hepatic injury. The levels of thiobarbituric acid reactive substances (TBARS, a marker of lipid peroxidation) and activities of hepatic antioxidant enzymes such as catalase (CAT) and glutathione-S-transferase (GST) were used to analyze the oxidative stress-mediated lipid peroxidation in liver sections. Our results showed that MTX administration significantly increased ALT, ASP, and ALP levels. TBARS, CAT, and GST levels were also markedly increased in liver after MTX administration. RVT treatment significantly prevented MTX-induced hepatotoxicity, as indicated by AST, ALT, and ALP levels and liver histopathology. Moreover, administration of RVT significantly decreased the elevated levels of TBARS and activities of CAT and GST in the liver compared to MTX-treated group. These results revealed that RVT may have a protective effect against MTX-induced hepatotoxicity by inhibiting oxidative stress-mediated lipid peroxidation. Consequently, RVT treatment might be a promising strategy against MTX-induced hepatotoxicity.

  16. Growth hormone and nutrition as protective agents against methotrexate induced enteritis.

    PubMed

    Ortega, M; de Segura, I A; Vázquez, I; López, J M; De Miguel, E

    2001-03-01

    To determine whether exogenously administered growth hormone can reduce or prevent chemotherapy-induced intestinal mucosa injury. The expected results will allow to consider its potential clinical use. Experimental and randomized study. Experimental Surgery Service, La Paz University Hospital. Adult Wistar rats weighing 250-300 g. A chemotherapy protocol with methotrexate (MTX) (120 mg/kg) was employed. Animals fed either with a normoproteic or a hyperproteic liquid diet were treated with either saline or growth hormone (1 mg/kg/day) since three days before until four days after chemotherapy. Animals were sacrificed seven days after MTX administration for tissue sampling. Co-administration of growth hormone and a hyperproteic diet increased intestinal crypt proliferation and reduced MTX-induced apoptosis. Jejunal mucosal structure (morphometry), proliferation (Ki-67) and apoptosis (TUNNEL) were assessed.

  17. Effects of growth hormone plus a hyperproteic diet on methotrexate-induced injury in rat intestines.

    PubMed

    Ortega, M; Gomez-de-Segura, I A; Vázquez, I; López, J M; de Guevara, C L; De-Miguel, E

    2001-01-01

    The aim of this study was to determine whether growth hormone treatment reduces injury to the intestinal mucosa induced by methotrexate (MTX). Wistar rats with intestinal injury induced by methotrexate were treated with daily growth hormone, beginning 3 days before MTX treatment until 3 or 4 days after MTX administration. The rats were killed at 3 or 7 days post-MTX administration. The rats were fed with either a normoproteic diet or a hyperproteic diet. Body weight, mortality, bacterial translocation, intestinal morphometry, proliferation and apoptosis and blood somatostatin and IGF-1 were determined. Combined administration of growth hormone and a hyperproteic diet reduces MTX-induced mortality. This effect was accompanied by increased cell proliferation and decreased apoptosis within the crypt. Morphometric data showed complete recovery of the mucosa by day 7 post-MTX administration. These results indicate a synergistic protective action of growth hormone combined with a hyperproteic diet to MTX-induced injury.

  18. Mitochondrial dysfunction and respiratory chain defects in a rodent model of methotrexate-induced enteritis.

    PubMed

    Kolli, V K; Natarajan, K; Isaac, B; Selvakumar, D; Abraham, P

    2014-10-01

    The efficacy of methotrexate (MTX), a widely used chemotherapeutic drug, is limited by its gastrointestinal toxicity and the mechanism of which is not clear. The present study investigates the possible role of mitochondrial damage in MTX-induced enteritis. Small intestinal injury was induced in Wistar rats by the administration of 7 mg kg(-1) body wt. MTX intraperitoneally for 3 consecutive days. MTX administration resulted in severe small intestinal injury and extensive damage to enterocyte mitochondria. Respiratory control ratio, the single most useful and reliable test of mitochondrial function, and 3-(4,5-dimethylthiazol-2-yll)-2,5-diphenyltetrazolium bromide reduction, a measure of cell viability were significantly reduced in all the fractions of MTX-treated rat enterocytes. A massive decrease (nearly 70%) in the activities of complexes II and IV was also observed. The results of the present study suggest that MTX-induced damage to enterocyte mitochondria may play a critical role in enteritis. MTX-induced alteration in mitochondrial structure may cause its dysfunction and decreases the activities of the electron chain complexes. MTX-induced mitochondrial damage can result in reduced adenosine triphosphate synthesis, thereby interfering with nutrient absorption and enterocyte renewal. This derangement may contribute to malabsorption of nutrients, diarrhea, and weight loss seen in patients on MTX chemotherapy.

  19. Potential protective effect of etanercept and aminoguanidine in methotrexate-induced hepatotoxicity and nephrotoxicity in rats.

    PubMed

    Hafez, Heba M; Ibrahim, Mohamed A; Ibrahim, Salwa A; Amin, Entesar F; Goma, Wafaey; Abdelrahman, Aly M

    2015-12-05

    Methotrexate (MTX), a chemotherapeutic and immunosuppressant drug, is generally well-tolerated by most patients. However, its cytotoxic nature contributes to life-threatening side effects including hepatotoxicity and nephrotoxicity. The present study investigated the possible role of tumor necrosis factor-alpha (TNF-α) inhibitor, etanercept and inducible nitric oxide synthase (iNOS) inhibitor, aminoguanidine, on MTX-induced hepatotoxicity and nephrotoxicity in rats. Rats were divided into 7 groups: control group, etanercept group, aminoguanidine group, MTX group, MTX+etanercept group, MTX+aminoguanidine group, and MTX+etanercept+aminoguanidine group. MTX caused hepatotoxicity and nephrotoxicity as evidenced biochemically by significant increase in serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea and creatinine, respectively as well as by histopathological changes. Such effects were associated with significant changes in oxidative stress markers (malondialdehyde (MDA), nitric oxide (NO), superoxide dismutase (SOD), catalase, and glutathione (GSH)) as well as by upregulation of TNF-α, iNOS and caspase-3 expressions in hepatic and renal tissues. Etanercept and aminoguanidine significantly attenuated MTX-hepatotoxicity and nephrotoxicity. The protective effect of either agent was associated with significant improvement in oxidative stress parameters as well as by downregulation of TNF-α, iNOS and caspase-3 expressions in hepatic and renal tissues. The study suggested that inhibitors of either TNF-α and/or iNOS have protective effect in MTX-induced hepatotoxicity and nephrotoxicity. The protective effect of either agent relies, at least partially, on their antioxidant effects and decreased TNF-α, iNOS, and caspase-3 expressions.

  20. Methotrexate-induced nonhealing cutaneous ulcers in a nonpsoriatic patient without pancytopenia

    PubMed Central

    Tekur, Venkatesh Krishnamurthy

    2016-01-01

    Methotrexate forms one of the main drugs in the pharmacological management of rheumatoid arthritis, psoriasis, and some neoplastic diseases. Methotrexate rarely causes cutaneous ulceration and most cases are reported in patients with psoriasis and have been accompanied by pancytopenia. The author here reports occurrence of multiple (two) cutaneous ulcers due to methotrexate in a nonpsoriatic patient. The patient was on methotrexate for seronegative rheumatoid arthritis for 10 years. To the best of the Author's knowledge, this is a rare case of cutaneous ulceration due to methotrexate in a nonpsoriatic patient reported in the literature so far, and probably one of its kind without pancytopenia or other hematological abnormalities. Stopping this medication led to complete healing of the ulcerated lesion in about four to six weeks. PMID:27730043

  1. Effect of Nigella sativa (black seeds) against methotrexate-induced nephrotoxicity in mice

    PubMed Central

    Ahmed, Jawad Hassan; Abdulmajeed, Isra Mohammed

    2017-01-01

    Aim: To evaluate the protective effect of Nigella sativa (NS) against nephrotoxicity of methotrexate (MTX) in mice. Materials and Methods: Four groups of Swiss albino male mice, eight in each group were used. The study was carried on between October 2014 and April 2015. Group 1 (control) were administered 0.3 ml distilled water orally daily for 21 days and injected with normal saline (0.25 ml) IP weekly. Group 2 (MTX group) were treated with MTX, 10 mg/kg IP weekly, while Group 3 were treated with 0.125 ml of NS oil by mouth daily and injected with normal saline (0.25 ml) IP weekly. Group 4 received 0.125 ml of NS oil by mouth daily and injected with 10 mg/kg MTX IP weekly. Oral treatments were administered using a special curved smooth tip nontraumatic metal needle and IP injections were given for 3 weeks at days 7, 14 and 21. Animals were sacrificed at day 23. Malondialdehyde (MDA) and glutathione (GSH) measurements were performed on kidney homogenate. Histopathology of the kidneys were prepared and examined. Results: MTX has resulted in a small elevation in MDA and reduction in GSH levels in kidney homogenate which was returned back to control values when NS and MTX were administered in combination. Statistical significance was achieved with elevation of GSH by MTX and NS compared to MTX alone. MTX caused histopathological changes suggesting nephrotoxicity in 6 animals out of 8, while no changes were found in all animals treated with MTX and NS. Conclusion: NS is protective against MTX-induced nephrotoxicity. PMID:28163954

  2. Methotrexate-Induced Neurotoxicity and Leukoencephalopathy in Childhood Acute Lymphoblastic Leukemia

    PubMed Central

    Bhojwani, Deepa; Sabin, Noah D.; Pei, Deqing; Yang, Jun J.; Khan, Raja B.; Panetta, John C.; Krull, Kevin R.; Inaba, Hiroto; Rubnitz, Jeffrey E.; Metzger, Monika L.; Howard, Scott C.; Ribeiro, Raul C.; Cheng, Cheng; Reddick, Wilburn E.; Jeha, Sima; Sandlund, John T.; Evans, William E.; Pui, Ching-Hon; Relling, Mary V.

    2014-01-01

    Purpose Methotrexate (MTX) can cause significant clinical neurotoxicity and asymptomatic leukoencephalopathy. We sought to identify clinical, pharmacokinetic, and genetic risk factors for these MTX-related toxicities during childhood acute lymphoblastic leukemia (ALL) therapy and provide data on safety of intrathecal and high-dose MTX rechallenge in patients with neurotoxicity. Patients and Methods Prospective brain magnetic resonance imaging was performed at four time points for 369 children with ALL treated in a contemporary study that included five courses of high-dose MTX and 13 to 25 doses of triple intrathecal therapy. Logistic regression modeling was used to evaluate clinical and pharmacokinetic factors, and a genome-wide association study (GWAS) was performed to identify germline polymorphisms for their association with neurotoxicities. Results Fourteen patients (3.8%) developed MTX-related clinical neurotoxicity. Of 13 patients rechallenged with intrathecal and/or high-dose MTX, 12 did not experience recurrence of neurotoxicity. Leukoencephalopathy was found in 73 (20.6%) of 355 asymptomatic patients and in all symptomatic patients and persisted in 74% of asymptomatic and 58% of symptomatic patients at the end of therapy. A high 42-hour plasma MTX to leucovorin ratio (measure of MTX exposure) was associated with increased risk of leukoencephalopathy in multivariable analysis (P = .038). GWAS revealed polymorphisms in genes enriched for neurodevelopmental pathways with plausible mechanistic roles in neurotoxicity. Conclusion MTX-related clinical neurotoxicity is transient, and most patients can receive subsequent MTX without recurrence of acute or subacute symptoms. All symptomatic patients and one in five asymptomatic patients develop leukoencephalopathy that can persist until the end of therapy. Polymorphisms in genes related to neurogenesis may contribute to susceptibility to MTX-related neurotoxicity. PMID:24550419

  3. Methotrexate-induced neurotoxicity and leukoencephalopathy in childhood acute lymphoblastic leukemia.

    PubMed

    Bhojwani, Deepa; Sabin, Noah D; Pei, Deqing; Yang, Jun J; Khan, Raja B; Panetta, John C; Krull, Kevin R; Inaba, Hiroto; Rubnitz, Jeffrey E; Metzger, Monika L; Howard, Scott C; Ribeiro, Raul C; Cheng, Cheng; Reddick, Wilburn E; Jeha, Sima; Sandlund, John T; Evans, William E; Pui, Ching-Hon; Relling, Mary V

    2014-03-20

    Methotrexate (MTX) can cause significant clinical neurotoxicity and asymptomatic leukoencephalopathy. We sought to identify clinical, pharmacokinetic, and genetic risk factors for these MTX-related toxicities during childhood acute lymphoblastic leukemia (ALL) therapy and provide data on safety of intrathecal and high-dose MTX rechallenge in patients with neurotoxicity. Prospective brain magnetic resonance imaging was performed at four time points for 369 children with ALL treated in a contemporary study that included five courses of high-dose MTX and 13 to 25 doses of triple intrathecal therapy. Logistic regression modeling was used to evaluate clinical and pharmacokinetic factors, and a genome-wide association study (GWAS) was performed to identify germline polymorphisms for their association with neurotoxicities. Fourteen patients (3.8%) developed MTX-related clinical neurotoxicity. Of 13 patients rechallenged with intrathecal and/or high-dose MTX, 12 did not experience recurrence of neurotoxicity. Leukoencephalopathy was found in 73 (20.6%) of 355 asymptomatic patients and in all symptomatic patients and persisted in 74% of asymptomatic and 58% of symptomatic patients at the end of therapy. A high 42-hour plasma MTX to leucovorin ratio (measure of MTX exposure) was associated with increased risk of leukoencephalopathy in multivariable analysis (P = .038). GWAS revealed polymorphisms in genes enriched for neurodevelopmental pathways with plausible mechanistic roles in neurotoxicity. MTX-related clinical neurotoxicity is transient, and most patients can receive subsequent MTX without recurrence of acute or subacute symptoms. All symptomatic patients and one in five asymptomatic patients develop leukoencephalopathy that can persist until the end of therapy. Polymorphisms in genes related to neurogenesis may contribute to susceptibility to MTX-related neurotoxicity.

  4. Saccharomyces boulardii ameliorates clarithromycin- and methotrexate-induced intestinal and hepatic injury in rats.

    PubMed

    Duman, Deniz Güney; Kumral, Zarife Nigâr Özdemir; Ercan, Feriha; Deniz, Mustafa; Can, Güray; Cağlayan Yeğen, Berrak

    2013-08-28

    Saccharomyces boulardii is a probiotic used for the prevention of antibiotic-associated diarrhoea. We aimed to investigate whether S. boulardii could alter the effects of clarithromycin (CLA) and methotrexate (MTX) on oro-caecal intestinal transit and oxidative damage in rats. Rats were divided into two groups receiving a single dose of MTX (20 mg/kg) or CLA (20 mg/kg per d) for 1 week. Groups were treated with either saline or S. boulardii (500 mg/kg) twice per d throughout the experiment. The control group was administered only saline. Following decapitation, intestinal transit and inflammation markers of glutathione (GSH), malondialdehyde and myeloperoxidase were measured in intestinal and hepatic tissues. CLA and MTX increased intestinal transit, while S. boulardii treatment slowed down CLA-facilitated transit back to control level. Both MTX and CLA increased lipid peroxidation while depleting the antioxidant GSH content in the hepatic and ileal tissues. Conversely, lipid peroxidation was depressed and GSH levels were increased in the ileal and hepatic tissues of S. boulardii-treated rats. Increased ileal neutrophil infiltration due to MTX and CLA treatments was also reduced by S. boulardii treatment. Histological analysis supported that S. boulardii protected intestinal tissues against the inflammatory effects of both agents. These findings suggest that S. boulardii ameliorates intestinal injury and the accompanying hepatic inflammation by supporting the antioxidant state of the tissues and by inhibiting the recruitment of neutrophils. Moreover, a preventive effect on MTXinduced toxicity is a novel finding of S. boulardii, proposing it as an adjunct to chemotherapy regimens.

  5. Tetramethylpyrazine identified by a network pharmacology approach ameliorates methotrexate-induced oxidative organ injury.

    PubMed

    Zhang, Bo; Lu, Cheng; Bai, Ming; He, Xiaojuan; Tan, Yong; Bian, Yanqin; Xiao, Cheng; Zhang, Ge; Lu, Aiping; Li, Shao

    2015-12-04

    Tetramethylpyrazine (TMP) is one of the active constituents extracted from a frequently used herb, Ligusticum wallichii Franchat (Chuan-Xiong in Chinese), in traditional Chinese medicine. TMP can exert multiple pharmacological actions such as anti-inflammatory, anti-oxidative damage, anti-platelet and neuroprotective effects, and its applications deserve further explored. This study aimed to determine the new role of TMP identified by a network pharmacology approach to alleviate the methotrexate (MTX)-induced oxidative injury and characterize their mechanism of combinational actions. A network pharmacology-based screening strategy is applied for target profile prediction and pharmacological characterization of herbal compounds, which is used to guide the following in vitro and in vivo experiments. The effect of herbal compounds identified by network pharmacology approaches to reduce the toxicity of MTX was assessed by MTX-induced rat toxicity model. The potential targets of TMP in this study were evaluated using standard protocols provided by Cerep, Inc. This strategy identified TMP from Ligusticum wallichii Franchat as a potent compound for ameliorating the oxidative organ injury of MTX. According to the predicted target profiles of TMP, a possible mechanism of the abrogation of MTX-induced toxicity is that TMP could upregulate cAMP by inhibiting phosphodiesterase (PDE) 10A2 activity. Another novel finding is that the competitive binding and antagonistic effects of TMP on adenosine receptor 2A and 2B appear to play important roles in the TMP-mediated reversal of MTX-induced hepatic injury. TMP identified by a network pharmacology approach could ameliorate MTX-induced oxidative organ injury. This study provides important evidence for the preclinical evaluation of TMP and MTX as a novel combinatorial remedy. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  6. Intervention of ginger or propolis ameliorates methotrexate-induced ileum toxicity.

    PubMed

    Abdul-Hamid, Manal; Salah, Marwa

    2016-02-01

    The long-term clinical use of methotrexate (MTX) is restricted due to its severe intestinal toxicity. The protective effect of ginger or propolis on the toxicity induced by MTX is relatively less understood, so the possible protective effect of ginger or propolis, used separately, was investigated. A total of 60 male albino rats were divided into six groups as follows: (1) control group; (2) ginger group; (3) propolis group; (4) MTX group; (5) ginger + MTX group; and (6) propolis + MTX group. The present results show that MTX caused ileum injury, including shortening and fusion of the villi, inflammatory cell infiltration and goblet cell depletion. Administration of ginger or propolis ameliorated the MTX-induced ileum injury as shown by histological, immunohistochemical and ultrastructural investigations and statistical analysis. This is revealed by intact villi, which shows marked increase in brown colouration of proliferating cell nuclear antigen positive nuclei in the crypts region, improvement in the number of goblet cells and brush border length of ileum. The current results conclude the efficacy and safety of ginger and propolis, which may be due to their antioxidant properties. © The Author(s) 2013.

  7. Clinical and radiological characteristics of methotrexate-induced acute encephalopathy in pediatric patients with cancer.

    PubMed

    Inaba, H; Khan, R B; Laningham, F H; Crews, K R; Pui, C-H; Daw, N C

    2008-01-01

    Little information is available about the diagnosis and management of acute methotrexate (MTX)-induced encephalopathy. We reviewed clinical and magnetic resonance imaging (MRI) [including diffusion-weighted imaging (DWI)] characteristics of this complication in pediatric cancer patients treated from 2000 to 2006. Six of 754 (0.8%) patients with leukemia or lymphoma and 2 of 44 (4.5%) with bone sarcoma experienced acute encephalopathy within 2 weeks (median, 7.5 days) after receiving high-dose i.v. and/or intrathecal MTX. The signs and symptoms varied at presentation and during episodes: hemiparesis (eight patients, alternating from side to side in four), dysphasia (six), confusion/emotionality (six), headache (three), choreoathetosis (two), and seizure (two). All patients recovered after 1-7 days (median, 5.5 days). DWI revealed restricted diffusion in anatomic brain regions associated with the symptoms; changes on T2-weighted and fluid-attenuated inversion recovery (FLAIR) imaging were consistently less marked. After recovery, DWI findings were normal but T2 and/or FLAIR imaging usually showed residual abnormalities. Acute MTX toxicity often manifests as fluctuating neurologic symptoms with alternating hemispheric involvement. Restricted diffusion on DWI is a reliable early sign of acute MTX encephalopathy and resolves as clinical status improves, despite the persistence of subtle abnormalities on MRI.

  8. Attenuation of Methotrexate-Induced Embryotoxicity and Oxidative Stress by Ethyl Pyruvate

    PubMed Central

    Najafi, Gholamreza; Atashfaraz, Elham; Farokhi, Farah

    2016-01-01

    Background Methotrexate (MTX), as an anti-folate agent, is widely used in the treatment of rheumatic disorders and malignant tumors, however it damages reproductive sys- tem in mice. The aim of this research was to study the effects of ethyl pyruvate (EP) on embryo development and oxidative stress changes in the testis of mice treated with MTX. Materials and Methods In this experimental study, thirty-two adult male Naval Medical Research Institute mice, with average weight of 26 ± 2 g, were divided into four groups. The first group (control) received distilled water (0.1 ml/mice/day), while the second group was intraperitoneally (IP) treated with 20 mg/kg MTX once per week. The third group was IP treated with 40 mg/kg/day EP, and the fourth group was IP treated with both 20 mg/kg MTX and 40 mg/kg/day EP for 30 days. At the end of treatment fertilization rate and embryonic development were evaluated. Differences between these groups were assessed by ANOVA using the SPSS software package for Windows with a Tukey-Kramer multiple post-hoc comparison test. Results MTX treatment caused significant (P<0.05) increase in malondialdehyde (MDA) and reduced catalase (CAT), as well as leading to in vitro fertilization (IVF) and embryonic development. The improved effects of EP on the IVF were determined by the reduced level of MDA (index of oxidative stress) and significant increased level of CAT (a key antioxidant). We observed significant increase in fertilization rate and embryonic development in the treated group with both MTX and EP. Conclusion It is suggested that EP can be useful in ameliorating testicular damages and embryotoxicity induced by MTX. These effects could be attributed to its antioxidant properties. PMID:27441057

  9. Methotrexate induces high level of apoptosis in canine lymphoma/leukemia cell lines.

    PubMed

    Pawlak, Aleksandra; Kutkowska, Justyna; Obmińska-Mrukowicz, Bożena; Rapak, Andrzej

    2017-09-28

    Methotrexate is an antimetabolite used in the treatment of cancer and non-malignant diseases including rheumatoid arthritis, psoriasis and graft vs. host disease. Combination therapy with methotrexate was successful in the treatment of canine lymphoma, mammary tumor and invasive urinary bladder cancer. Lymphoma, the most common hematopoietic cancer in dogs, and leukemia are sensitive to chemotherapy, which is why methotrexate may be an important treatment option for these diseases. Although methotrexate is already used in veterinary oncology its effects on canine cancer cells has not been tested. The aim of the study was to evaluate for the first time methotrexate concentration-dependent cytotoxicity and its capability of inducing apoptosis in selected canine lymphoma/leukemia cell lines: CLBL-1, GL-1 and CL-1 as a first step before the in vitro development of new therapeutic options with the use of methotrexate. Methotrexate exhibited concentration-dependent inhibitory effect on proliferation of all the examined cell lines with different degree of apoptosis induction. The most methotrexate sensitive cells belonged to CL-1 cell line derived from T cell neoplasia and previously characterized by high resistance to the majority of anticancer drugs used in the therapy of lymphoma/leukemia in dogs. Canine lymphoma and leukemia cell lines are sensitive to methotrexate, and this drug may be useful in effective treatment of canine neoplasms and especially of T-type leukemia/lymphoma. Copyright © 2017. Published by Elsevier Ltd.

  10. Frequency of micronuclei and of other nuclear abnormalities in erythrocytes of the grey mullet from the Mondego, Douro and Ave estuaries--Portugal.

    PubMed

    Carrola, João; Santos, Nádia; Rocha, Maria J; Fontainhas-Fernandes, António; Pardal, Miguel A; Monteiro, Rogério A F; Rocha, Eduardo

    2014-05-01

    Fish are bioindicators of water pollution, and an increased rate of their erythrocyte nuclear morphological abnormalities (ENMAs)-and particularly of erythrocyte micronuclei (EMN)-is used as a genotoxicity biomarker. Despite the potential value of ENMAs and MN, there is scarce information about fish captured in Iberian estuaries. This is the case of the Portuguese estuaries of the Mondego, Douro and Ave, suffering from different levels of environmental stress and where chemical surveys have been disclosing significant amounts of certain pollutants. So, the aim of this study was to evaluate genotoxicants impacts and infer about the exposure at those ecosystems, using the grey mullet (Mugil cephalus) as bioindicator and considering the type and frequency of nuclear abnormalities of erythrocytes as proxies of genotoxicity. Sampling of mullets was done throughout the year in the important Mondego, Douro and Ave River estuaries (centre and north-western Portugal). The fish (total n = 242) were caught in campaigns made in spring-summer and autumn-winter, using nets or fishing rods. The sampled mullets were comparable between locations in terms of the basic biometric parameters. Blood smears were stained with Diff-Quik to assess the frequencies of six types of ENMAs and MN (given per 1,000 erythrocytes). Some basic water physicochemical parameters were recorded to search for fluctuations matching the ENMAs. Overall, the most frequent nucleus abnormality was the polymorphic type, sequentially followed by the blebbed/lobed/notched, segmented, kidney shaped, vacuolated, MN and binucleated. The total average frequency of the ENMAs ranged from 73 ‰ in the Mondego to 108 ‰ in the Ave. The polymorphic type was typically ≥50 % of the total ENMAs, averaging about 51 ‰, when considering all three estuaries. The most serious lesion-the MN-in fish from Mondego and Douro had a similar frequency (≈0.38 ‰), which was significantly lower than that in the Ave (0

  11. Induction and disappearance of γH2AX foci and formation of micronuclei after exposure of human lymphocytes to ⁶⁰Co γ-rays and p(66)+ Be(40) neutrons.

    PubMed

    Vandersickel, Veerle; Beukes, Philip; Van Bockstaele, Bram; Depuydt, Julie; Vral, Anne; Slabbert, Jacobus

    2014-02-01

    To investigate both the formation of micronuclei (MN) and the induction and subsequent loss of phosphorylated histone H2AX foci (γH2AX foci) after in vitro exposure of human lymphocytes to either (60)Co γ-rays or p(66)+ Be(40) neutrons. MN dose response (DR) curves were obtained by exposing isolated lymphocytes of 10 different donors to doses ranging from 0-4 Gy γ-rays or 0-2 Gy neutrons. Also, γH2AX foci DR curves were obtained following exposure to doses ranging from 0-0.5 Gy of either γ-rays or neutrons. Foci kinetics for lymphocytes for a single donor exposed to 0.5 Gy γ-rays or neutrons were studied up to 24 hours post-irradiation. Micronuclei yields following neutron exposure were consistently higher compared to that from (60)Co γ-rays. All MN yields were over-dispersed compared to a Poisson distribution. Over-dispersion was higher after neutron irradiation for all doses > 0.1 Gy. Up to 4 hours post-irradiation lower yields of neutron-induced γH2AX foci were observed. Between 4 and 24 hours the numbers of foci from neutrons were consistently higher than that from γ-rays. The half-live of foci disappearance is only marginally longer for neutrons compared to that from γ-rays. Foci formations were more likely to be over-dispersed for neutron irradiations. Although neutrons are more effective to induce MN, the absolute number of induced γH2AX foci are less at first compared to γ-rays. With time neutron-induced foci are more persistent. These findings are helpful for using γH2AX foci in biodosimetry and to understand the repair of neutron-induced cellular damage.

  12. HUman MicroNucleus project: international database comparison for results with the cytokinesis-block micronucleus assay in human lymphocytes: I. Effect of laboratory protocol, scoring criteria, and host factors on the frequency of micronuclei.

    PubMed

    Bonassi, S; Fenech, M; Lando, C; Lin, Y P; Ceppi, M; Chang, W P; Holland, N; Kirsch-Volders, M; Zeiger, E; Ban, S; Barale, R; Bigatti, M P; Bolognesi, C; Jia, C; Di Giorgio, M; Ferguson, L R; Fucic, A; Lima, O G; Hrelia, P; Krishnaja, A P; Lee, T K; Migliore, L; Mikhalevich, L; Mirkova, E; Mosesso, P; Müller, W U; Odagiri, Y; Scarffi, M R; Szabova, E; Vorobtsova, I; Vral, A; Zijno, A

    2001-01-01

    Micronucleus (MN) expression in peripheral blood lymphocytes is well established as a standard method for monitoring chromosome damage in human populations. The first results of an analysis of pooled data from laboratories using the cytokinesis-block micronucleus (CBMN) assay and participating in the HUMN (HUman MicroNucleus project) international collaborative study are presented. The effects of laboratory protocol, scoring criteria, and host factors on baseline micronucleated binucleate cell (MNC) frequency are evaluated, and a reference range of "normal" values against which future studies may be compared is provided. Primary data from historical records were submitted by 25 laboratories distributed in 16 countries. This resulted in a database of nearly 7000 subjects. Potentially significant differences were present in the methods used by participating laboratories, such as in the type of culture medium, the concentration of cytochalasin-B, the percentage of fetal calf serum, and in the culture method. Differences in criteria for scoring micronuclei were also evident. The overall median MNC frequency in nonexposed (i.e., normal) subjects was 6.5 per thousand and the interquartile range was between 3 and 12 per thousand. An increase in MNC frequency with age was evident in all but two laboratories. The effect of gender, although not so evident in all databases, was also present, with females having a 19% higher level of MNC frequency (95% confidence interval: 14-24%). Statistical analyses were performed using random-effects models for correlated data. Our best model, which included exposure to genotoxic factors, host factors, methods, and scoring criteria, explained 75% of the total variance, with the largest contribution attributable to laboratory methods.

  13. A comparative study of the anticlastogenic effects of chlorophyllin on N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) or 7,12-dimethylbenz (α) anthracene (DMBA) induced micronuclei in mammalian cells in vitro and in vivo.

    PubMed

    Grossi, Maria Rosaria; Berni, Andrea; Pepe, Gaetano; Filippi, Silvia; Mosesso, Pasquale; Shivnani, Anaadi Amar; Papeschi, Cristiano; Natarajan, Adayapalam T; Palitti, Fabrizio

    2012-11-15

    Chlorophyllin (CHL), a water soluble derivative of chlorophyll has been shown to have both anticarcinogenic and antigenotoxic properties. We evaluated the protective effects of CHL (25μM in vitro, 4 and 100mg/kg. b.w.) on the clastogenic action of two model carcinogens, MNNG and DMBA (25μM and 2μM respectively) in vitro on human hepatoma cells (HepG2) and (40mg and 25mg/Kg/b.w. respectively) in vivo on bone marrow of mice, using the frequencies of induced micronuclei as the end point. Pre-, post- and simultaneous treatments with CHL and the carcinogen were carried out in vitro. With MNNG, only simultaneous treatment with CHL was effective in reducing the frequencies of MN, suggesting a direct interaction between CHL and MNNG. A statistically significant reduction in of DMBA induced MN was found by pre-or post treatment with CHL while a reduction (not significant) was observed by simultaneous treatment. In in vivo experiments, CHL pre-treatment did not affect the frequencies of MN in PCEs of bone marrow induced by MNNG or DMBA. However, increased the toxic effect of DMBA (reduction in percent of PCEs) was accompanied by a reduction in the induced frequencies of MN. CHL was not clastogenic in both in vitro and in vivo tests. It can be concluded that (a) CHL has a protective effect against MNNG and DMBA. This effect is dependent upon the protocol employed in in vitro experiments. In vivo, CHL did not have a protective effect against MNNG and DMBA. A protective effect of CHL against DMBA was evident only at high toxic levels.

  14. Micronuclei, hemoglobin adducts and respiratory tract irritation in mice after inhalation of toluene diisocyanate (TDI) and 4,4'-methylenediphenyl diisocyanate (MDI).

    PubMed

    Lindberg, Hanna K; Korpi, Anne; Santonen, Tiina; Säkkinen, Kirsi; Järvelä, Merja; Tornaeus, Jarkko; Ahonen, Niina; Järventaus, Hilkka; Pasanen, Anna-Liisa; Rosenberg, Christina; Norppa, Hannu

    2011-07-14

    Toluene diisocyanate (TDI) and 4,4'-methylenediphenyl diisocyanate (MDI), used in the production of polyurethane foam, are well known for their irritating and sensitizing properties. Contradictory results have been obtained on their genotoxicity. We investigated the genotoxicity and protein binding of inhaled TDI and MDI in mice by examining micronucleated polychromatic erythrocytes (PCEs) in bone marrow and peripheral blood and TDI- and MDI-derived adducts in hemoglobin. Male C57Bl/6J mice (8 per group) were exposed head-only to TDI vapour (mean concentrations 1.1, 1.5, and 2.4mg/m(3); the mixture of isomers contained, on the average, 63% 2,4-TDI and 37% 2,6-TDI) or MDI aerosol (mean concentrations 10.7, 20.9 and 23.3mg/m(3)), during 1h/day for 5 consecutive days. Bone marrow and peripheral blood were collected 24h after the last exposure. Inhalation of TDI caused sensory irritation (SI) in the upper respiratory tract, and cumulative effects were observed at the highest exposure level. Inhalation of MDI produced SI and airflow limitation, and influx of inflammatory cells into the lungs. Hemoglobin adducts detected in the exposed mice resulted from direct binding to globin of 2,4- and 2,6-TDI and MDI, and dose-dependent increases were observed especially for 2,4-TDI-derived adducts. Adducts originating from the diamines of TDI (toluene diamine) or MDI (methylene dianiline) were not observed. No significant increase in the frequency of micronucleated PCEs was detected in the bone marrow or peripheral blood of the mice exposed to TDI or MDI. The ratio of PCEs and normochromatic erythrocytes (NCEs) was reduced at the highest concentration of MDI, and a slight reduction of the PCE/NCE ratio, dependent on cumulative inhaled dose, was also seen with TDI. Our results indicate that inhalation of TDI or MDI (1h/day for 5 days), at levels that induce toxic effects and formation of TDI- or MDI-specific adducts in hemoglobin, does not have detectable genotoxic effects in mice

  15. Nonrandom distribution of methotrexate-induced aberrations on human chromosomes. Detection of further folic acid sensitive fragile sites.

    PubMed

    Barbi, G; Steinbach, P; Vogel, W

    1984-01-01

    Eleven folic acid sensitive fragile sites (3p14, 7p13, 7q31.1, 7q32, 9q32, 11p13, 14q23, 15q22, 16q23, Xp22.2, Xq22) were detected in one individual, eight of them previously unknown. These sites seem to bear each its specific sensitivity to folic acid deficiency. Six of the sites were observed simultaneously on both homologous chromosomes in at least one cell. Each of these 11 sites was also found in at least one among 12 individuals further examined. Some of these individuals showed six of these 11 sites. The fragile site 3p14 was detected in all individuals examined. The homologous sites 3p14 of one individual differed from each other in their frequency of lesions induced by methotrexate as well as fluorodeoxyuridine. This observation suggests that folic acid sensitivity is a property inherent in the chromatin of an individual chromosome at the site involved in fragility. This property seems to be responsible for the nonrandom fragility at that site and also for the individual sensitivity of each chromosomal site.

  16. Cytoprotective effects of amifostine, ascorbic acid and N-acetylcysteine against methotrexate-induced hepatotoxicity in rats

    PubMed Central

    Akbulut, Sami; Elbe, Hulya; Eris, Cengiz; Dogan, Zumrut; Toprak, Gulten; Otan, Emrah; Erdemli, Erman; Turkoz, Yusuf

    2014-01-01

    AIM: To investigate the potential role of oxidative stress and the possible therapeutic effects of N-acetyl cysteine (NAC), amifostine (AMF) and ascorbic acid (ASC) in methotrexate (MTX)-induced hepatotoxicity. METHODS: An MTX-induced hepatotoxicity model was established in 44 male Sprague Dawley rats by administration of a single intraperitoneal injection of 20 mg/kg MTX. Eleven of the rats were left untreated (Model group; n = 11), and the remaining rats were treated with a 7-d course of 50 mg/kg per day NAC (MTX + NAC group; n = 11), 50 mg/kg per single dose AMF (MTX + AMF group; n = 11), or 10 mg/kg per day ASC (MTX + ASC group; n = 11). Eleven rats that received no MTX and no treatments served as the negative control group. Structural and functional changes related to MTX- and the various treatments were assessed by histopathological analysis of liver tissues and biochemical assays of malondialdehyde (MDA), superoxide dismutase (SOD), catalase, glutathione (GSH) and xanthine oxidase activities and of serum levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and total bilirubin. RESULTS: Exposure to MTX caused structural and functional hepatotoxicity, as evidenced by significantly worse histopathological scores [median (range) injury score: control group: 1 (0-3) vs 7 (6-9), P = 0.001] and significantly higher MDA activity [409 (352-466) nmol/g vs 455.5 (419-516) nmol/g, P < 0.05]. The extent of MTX-induced perturbation of both parameters was reduced by all three cytoprotective agents, but only the reduction in hepatotoxicity scores reached statistical significance [4 (3-6) for NAC, 4.5 (3-5) for AMF and 6 (5-6) for ASC; P = 0.001, P = 0.001 and P < 0.005 vs model group respectively]. Exposure to MTX also caused a significant reduction in the activities of GSH and SOD antioxidants in liver tissues [control group: 3.02 (2.85-3.43) μmol/g and 71.78 (61.88-97.81) U/g vs model group: 2.52 (2.07-3.34) μmol/g and 61.46 (58.27-67.75) U/g, P < 0.05]; however, only the NAC treatment provided significant increases in these antioxidant enzyme activities [3.22 (2.54-3.62) μmol/g and 69.22 (61.13-100.88) U/g, P < 0.05 and P < 0.01 vs model group respectively]. CONCLUSION: MTX-induced structural and functional damage to hepatic tissues in rats may involve oxidative stress, and cytoprotective agents (NAC > AMF > ASC) may alleviate MTX hepatotoxicity. PMID:25110444

  17. Reduction of oxidative stress by an ethanolic extract of leaves of Piper betle (Paan) Linn. decreased methotrexate-induced toxicity.

    PubMed

    De, Soumita; Sen, Tuhinadri; Chatterjee, Mitali

    2015-11-01

    Methotrexate (MTX), a folate antagonist, is currently used as first line therapy for autoimmune diseases like rheumatoid arthritis and psoriasis, but its use is limited by the associated hepatotoxicity. As leaves of Piper betle, belonging to family Piperaceae, have antioxidant and anti-inflammatory properties, the present study was undertaken to investigate the potential of Piper betle leaf extract (PB) in attenuating MTX-induced hepatotoxicity. Rats pre-treated with PB (50 or 100 mg kg(-1) b.w., p.o.) were administered with a single dose of MTX (20 mg kg(-1), b.w., i.p.) and its hepatoprotective efficacy was compared with folic acid (1 mg kg(-1) b.w., i.p.), conventionally used to minimize MTX-induced toxicity. MTX-induced hepatotoxicity was confirmed by increased activities of marker enzymes, alanine transaminase, aspartate transaminase, and alkaline phosphatase which were remitted by pre-treatment with PB and corroborated with histopathology. Additionally, MTX-induced hepatic oxidative stress which included increased generation of reactive oxygen species, enhanced lipid peroxidation, depleted levels of glutathione and decreased activities of antioxidant enzymes was effectively mitigated by PB, indicative that its promising antioxidant-mediated hepatoprotective activity was worthy of future pharmacological consideration.

  18. Significance of liver biopsy for the evaluation of methotrexate-induced liver damage in patients with rheumatoid arthritis

    PubMed Central

    Osuga, Tatsuya; Ikura, Yoshihiro; Kadota, Chikara; Hirano, Seiichi; Iwai, Yasuhiro; Hayakumo, Takanobu

    2015-01-01

    It is well recognized that long-term administration of methotrexate (MTX) in patients with rheumatoid arthritis (RA) can induce liver fibrosis via a steatohepatitis-like inflammatory process. Several non-invasive tests have been investigated as alternatives to liver biopsy, which is, however, still recognized as a final diagnostic modality to detect the MTX-induced liver damage. To clarify whether there is a significant discrepancy between clinical estimations and pathologic findings of this hepatic condition, we performed a following comparative study. Four RA patients (4 women, age 67-80 yr) with MTX-induced liver damage were reviewed. The severity of hepatic damage estimated clinically was compared with histopathologic findings. Consequently, the liver biopsies showed the relatively earlier stages of and milder degrees of hepatic damages than the clinical estimations. The histopathologic findings were more reliable and useful than any other clinical examinations, to plan and modify the treatment strategies, especially in cases of liver damages with multiple etiologies besides MTX. These findings suggest that liver biopsy is an unavoidable examination to assess precisely MTX-induced liver damage. Non-invasive tests may be useful to monitor the hepatic condition of RA patients receiving MTX but do not constitute an acceptable alternative to liver biopsy. PMID:25973089

  19. Methotrexate-induced mucositis in acute leukemia patients is not associated with the MTHFR 677T allele in Mexico.

    PubMed

    Ruiz-Argüelles, Guillermo J; Coconi-Linares, Lucia Nancy; Garcés-Eisele, Javier; Reyes-Núñez, Virginia

    2007-10-01

    Methylenetetrahydrofolate reductase (MTHFR) has two common variants with reduced activity due to polymorphisms at nucleotides 677 and 1298. Both affect folate metabolism and thus remethylation of homocysteine, but are also thought to affect nucleotide synthesis and DNA methylation. Methotrexate (MTX), which interrupts folate metabolism, is used in the treatment of a variety of diseases including acute lymphoblastic leukemia (ALL), but exerts in some patients toxic effects on fast dividing tissues such as mucosal epithelia. The enhanced toxicity may be due to cooperative effects between MTX and MTHFR variants. Accordingly, it has been reported that carrying the 677T allele of the MTHFR is a risk factor for MTX-associated mucositis. As in the Mexican population, which is characterized by a high prevalence of the 677T MTHFR variant, several of its commonly associated defects have not been observed, we investigated the relationship between MTX toxicity and the 677T allele. Out of 28 patients with ALL (CC: 2, CT: 10, TT: 16), 16 had episodes of MTX-associated mucositis (CC: 0, CT: 6, TT: 10). Neither at the gene level nor at the genotype level was a significant association with mucositis found. It may be postulated that the risk of higher MTX toxicity in patients with decreased MTHFR activity could be neutralized by the normally folate rich diet in Mexico.

  20. Methotrexate induces seizure and decreases glutamate uptake in brain slices: prevention by ionotropic glutamate receptors antagonists and adenosine.

    PubMed

    Leke, R; Oliveira, D L; Schmidt, A P; Avila, T T; Jorge, R S; Fischer, A; Wofchuk, S; Souza, D O; Portela, L V

    2006-12-03

    Methotrexate (MTX)-induced neurotoxicity may occur after intrathecal or systemic administration at low, intermediate and high doses for the treatment of malignant or inflammatory diseases. The mechanisms of MTX neurotoxicity are not totally understood, and appear to be multifactorial. In this study we characterized a model of MTX-induced seizures in mice to evaluate the convulsive and toxic MTX properties. Additionally, the effect of MTX-induced seizures on the activity of glutamate transporters, as well as the anticonvulsant role of MK-801, DNQX and adenosine on glutamate uptake in brain slices was investigated . MTX induced tonic-clonic seizures in approximately 95% of animals and pre-treatment with MK-801, DNQX and adenosine prevented seizure in 80%, 62% and 50% of animals, respectively. Moreover, MTX leads 59% of mice to death, which was prevented in 100% and 94% when animals received MK-801 and DNQX, respectively. Glutamate uptake decreased by 20% to 30% in cortical slices after MTX-induced seizures. Interestingly, when seizures were prevented by MK-801, DNQX or adenosine, glutamate uptake activity remained at the same level as the control group. Thus, our results demonstrate the involvement of the glutamatergic system in MTX-induced seizures.

  1. Efficacy of royal jelly on methotrexate-induced systemic oxidative stress and damage to small intestine in rats.

    PubMed

    Kaynar, Leylagül; Cetin, Aysun; Hacioglu, Sibel K; Eser, Barış; Koçyigit, İsmail; Canöz, Özlem; Tasdemir, Arzu; Karadag, Canan; Kurnaz, Fatih; Saraymen, Recep; Silici, Sibel

    2012-01-01

    The aim of this present study is to investigate the mucositis caused by methotrexate (MTX), as well as whether the application of royal jelly (RJ) has a protective effect on oxidative stress. This present study included six groups each consisted of 12 Wistar rats. Distilled water (po: peroral) was given to the 1st group as placebo for 10 days and MTX (20 mg/kg, intraperitoneal: ip) on the 7th day. The 2nd group received RJ (50mg/kg, po) for 10 days and normal saline (NS) instead of MTX. RJ (50mg/kg) was given to the 3rd group for 10 days and MTX on the 7th day. The 4th group received RJ (100 mg/kg, po) for 10 days and NS was given intraperitoneally. RJ (100mg/kg) was given to the 5th group for 10 days and a single dose of MTX. Distilled water was given to the 6th (control) group for 10 days and intraperitoneal NS on the 7th day. Malondialdehyde (MDA), glutathione peroxidase and superoxide dismutase were analyzed in blood samples on the 11th day. Morphological and histopathological changes were examined in the intestinal tissue samples. Villus length and mucosal thickness, as well as the villus length/crypt ratio, were significantly decreased with MTX administration, and the semi-quantitative histological evaluation (SQHE) score was measured high (p<0.001). In addition, a decrease in the antioxidant parameters and an increase in the MDA levels were identified. The villus length and SQHE were significantly different in the groups receiving RJ (p<0.001) as compared to the MTX group. Although RJ addition had no effect on the decreased mucosal thickness and villus/crypt ratio in MTX groups, it caused an improvement in the antioxidant levels and a remarkable decrease in MDA levels. Adding RJ has a decreasing effect on the MTX-induced intestinal damage and it has a suppressive effect on MTX-induced oxidative stress by means of increasing antioxidant enzyme activity and decreasing lipid peroxidation.

  2. Low-dose methotrexate-induced acute interstitial pneumonitis: Report of two cases from South India and review of literature

    PubMed Central

    Iyyadurai, Ramya; Carey, Ronald Albert Benton; Satyendra, Sowmya

    2016-01-01

    Methotrexate (MTX) is an antimetabolite used as a disease-modifying agent for various rheumatological conditions. We report two patients who were treated with daily low-dose MTX and developed acute interstitial pneumonitis requiring hospital admission. MTX-induced pneumonitis is a rare life-threatening side effect, high index of clinical suspicion is required, treatment is mainly withdrawal of MTX, supportive therapy, and adjunctive steroids, outcome is good if condition is recognized early, and appropriate treatment is given. PMID:28349012

  3. Lutein protects against methotrexate-induced and reactive oxygen species-mediated apoptotic cell injury of IEC-6 cells.

    PubMed

    Chang, Chi-Jen; Lin, Ji-Fan; Chang, Hsun-Hsien; Lee, Gon-Ann; Hung, Chi-Feng

    2013-01-01

    High-dose chemotherapy using methotrexate (MTX) frequently induces side effects such as mucositis that leads to intestinal damage and diarrhea. Several natural compounds have been demonstrated of their effectiveness in protecting intestinal epithelial cells from these adverse effects. In this paper, we investigated the protection mechanism of lutein against MTX-induced damage in IEC-6 cells originating from the rat jejunum crypt. The cell viability, induced-apoptosis, reactive oxygen species (ROS) generation, and mitochondrial membrane potential in IEC-6 cells under MTX treatment were examined in the presence or absence of lutein. Expression level of Bcl2, Bad and ROS scavenging enzymes (including SOD, catalase and Prdx1) were detected by quantitative RT-PCR. The cell viability of IEC-6 cells exposed to MTX was decreased in a dose- and time-dependent manner. MTX induces mitochondrial membrane potential loss, ROS generation and caspase 3 activation in IEC-6 cells. The cytotoxicity of MTX was reduced in IEC-6 cells by the 24 h pre-treatment of lutein. We found that pre-treatment of lutein significantly reduces MTX-induced ROS and apoptosis. The expression of SOD was up-regulated by the pre-treatment of lutein in the MTX-treated IEC-6 cells. These results indicated that lutein can protect IEC-6 cells from the chemo-drugs induced damage through increasing ROS scavenging ability. The MTX-induced apoptosis of IEC-6 cells was shown to be repressed by the pre-treatment of lutein, which may represent a promising adjunct to conventional chemotherapy for preventing intestinal damages.

  4. Lutein Protects against Methotrexate-Induced and Reactive Oxygen Species-Mediated Apoptotic Cell Injury of IEC-6 Cells

    PubMed Central

    Chang, Chi-Jen; Lin, Ji-Fan; Chang, Hsun-Hsien; Lee, Gon-Ann; Hung, Chi-Feng

    2013-01-01

    Purpose High-dose chemotherapy using methotrexate (MTX) frequently induces side effects such as mucositis that leads to intestinal damage and diarrhea. Several natural compounds have been demonstrated of their effectiveness in protecting intestinal epithelial cells from these adverse effects. In this paper, we investigated the protection mechanism of lutein against MTX-induced damage in IEC-6 cells originating from the rat jejunum crypt. Methods The cell viability, induced-apoptosis, reactive oxygen species (ROS) generation, and mitochondrial membrane potential in IEC-6 cells under MTX treatment were examined in the presence or absence of lutein. Expression level of Bcl2, Bad and ROS scavenging enzymes (including SOD, catalase and Prdx1) were detected by quantitative RT-PCR. Results The cell viability of IEC-6 cells exposed to MTX was decreased in a dose- and time-dependent manner. MTX induces mitochondrial membrane potential loss, ROS generation and caspase 3 activation in IEC-6 cells. The cytotoxicity of MTX was reduced in IEC-6 cells by the 24 h pre-treatment of lutein. We found that pre-treatment of lutein significantly reduces MTX-induced ROS and apoptosis. The expression of SOD was up-regulated by the pre-treatment of lutein in the MTX-treated IEC-6 cells. These results indicated that lutein can protect IEC-6 cells from the chemo-drugs induced damage through increasing ROS scavenging ability. Conclusion The MTX-induced apoptosis of IEC-6 cells was shown to be repressed by the pre-treatment of lutein, which may represent a promising adjunct to conventional chemotherapy for preventing intestinal damages. PMID:24039779

  5. Impact of methylenetetrahydrofolate reductase (MTHFR) polymorphisms on methotrexate-induced toxicities in acute lymphoblastic leukemia: a meta-analysis.

    PubMed

    Yang, Lin; Hu, Xin; Xu, Luhang

    2012-10-01

    The associations between methylenetetrahydrofolate reductase (MTHFR) polymorphism and methotrexate (MTX)-induced toxicities in patients with acute lymphoblastic leukemia (ALL) have been evaluated in various populations, with the results remained conflicting. Therefore, we conducted a meta-analysis by combining available data to derive a more precise estimation of the association. PubMed, Embase, and China National Knowledge Infrastructure were searched until 21 September 2011 to identify eligible studies. A total of 14 studies were included, with all studies investigating MTHFR C677T polymorphism while nine of them investigating MTHFR A1298C polymorphism only. Results suggested that MTHFR C677T polymorphism was associated with significantly increased risk of MTX-induced toxicity, specifically liver toxicity (TT/CT vs. CC: odds ratio (OR) = 1.70, 95 % confidence interval (CI) = 1.05-2.75), myelosuppression (TT vs. CT/CC: OR = 2.82, 95 %CI = 1.25-6.34), oral mucositis (TT/CT vs. CC: OR = 3.68, 95 %CI = 1.73-7.85), gastrointestinal toxicity (TT/CT vs. CC: OR = 2.36, 95 %CI = 1.36-4.11), and skin toxicity (T vs. C: OR = 2.26, 95 %CI = 1.07-4.74). MTHFR A1298C polymorphism was found to be associated with decreased risk of skin toxicity (CC/AC vs. AA: OR = 0.11, 95 %CI = 0.01-0.85). Genotyping of MTHFR polymorphism, C677T particularly, prior to treatment for ALL is likely to be useful with the aim of tailoring MTX therapy and thus reducing the MTX-related toxicities. However, further studies with larger data set and well-designed models are required to validate our findings.

  6. Effect of captopril and telmisartan on methotrexate-induced hepatotoxicity in rats: impact of oxidative stress, inflammation and apoptosis.

    PubMed

    Kelleni, Mina T; Ibrahim, Salwa A; Abdelrahman, Aly M

    2016-06-01

    Methotrexate (MTX) is a commonly used antineoplastic and anti-rheumatoid drug whose efficacy is limited by its hepatotoxicity. The aim of this study was to investigate the possible protective role of captopril (100 mg/kg/day, p.o. for seven days), an angiotensin converting enzyme inhibitor, and telmisartan (10 mg/kg/day p.o. for seven days), an angiotensin II receptor blocker with peroxisome proliferative receptor gamma (PPARγ) agonism, in a model of MTX (single dose 20 mg/kg i.p. at the fifth day) induced hepatotoxicity in rats. Results of the present study revealed MTX-induced hepatotoxicity as demonstrated by increased level of liver enzymes and confirmed by histopathology. Pretreatment with captopril or telmisartan produced a significant hepatic protection manifested as a significant (p < 0.05) decrease in serum levels of alanine transferase (ALT) and aspartate transferase (AST) and alkaline phosphatase (ALP) enzymes; hepatic malondialdehyde (MDA) and total nitrites and nitrates (NOx) levels; as well as a significant increase in hepatic superoxide dismutase (SOD) activity. In addition, there was a remarkable improvement in the histopathological features and a significant reduction in the expression of COX-2, iNOS and caspase-3 enzymes as compared with the MTX group. We recommend considering captopril/Telmisartan, if tolerated and not contraindicated, as preferable antihypertensive agents in patients receiving MTX in their chemotherapy protocols.

  7. Mutagenicity and disinfection by-products in surface drinking water disinfected with peracetic acid.

    PubMed

    Monarca, Silvano; Richardson, Susan D; Feretti, Donatella; Grottolo, Mario; Thruston, Alfred D; Zani, Claudia; Navazio, Giancarlo; Ragazzo, Patrizia; Zerbini, Ilaria; Alberti, Adriana

    2002-02-01

    The aims of this research were to study the influence of peracetic acid (PAA) on the formation of mutagens in surface waters used for human consumption and to assess its potential application for the disinfection of drinking water. The results obtained using PAA were compared to those found with sodium hypochlorite (NaClO) and chlorine dioxide (ClO2). The Ames test, root anaphase aberration assay, and root/micronuclei assay in Allium cepa and Tradescantia/micronuclei test were used to evaluate the mutagenicity of disinfected samples. Microbiological tests were also performed, and disinfection by-products (DBPs) were identified using gas chromatography/mass spectrometry (GC/MS). A slight bacterial mutagenicity was found in raw lake and river water, and similar activity was detected in disinfected samples. A plant test revealed genotoxicity in raw river water, and microbiological analysis showed that PAA has bactericidal activity but lower than that of the other disinfectants. The DBPs produced by PAA were mainly carboxylic acids, which are not recognized as mutagenic, whereas the waters treated with the other disinfectants showed the presence of mutagenic/carcinogenic halogenated DBPs. However, additional experiments should be performed with higher concentrations of PAA and using water with higher organic carbon content to better evaluate this disinfectant.

  8. Cytogenetic analysis of Pakistani individuals occupationally exposed to pesticides in a pesticide production industry.

    PubMed

    Bhalli, Javed A; Khan, Q M; Haq, M A; Khalid, A M; Nasim, A

    2006-03-01

    Although several cytogenetic biomonitoring studies on workers exposed to pesticides have been reported, there is only limited information on this topic from developing countries where pesticides have been widely used over the years. People in developing countries are at higher risk from exposure, due to poor working conditions and a lack of awareness of the potential hazards during manufacturing and application of the pesticides. The present study has assessed the genotoxic effects of pesticides on workers involved in the pesticide manufacturing industry. Subjects in the exposed group (29) were drawn from workers at a pesticide production plant in district Multan (Pakistan). The control group (unexposed) composed of 35 individuals from the same area but was not involved in pesticide production. Liver enzymes, serum cholinesterase (SChE), micronucleus assay and some haematological parameters were used as biomarkers in this study. A statistically significant (P < 0.001) increase in levels of alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase was detected in exposed workers with respect to the control group. There was a significant (P < 0.001) decrease in the level of SChE in the exposed group. Exposed individuals exhibited cytogenetic damage with increased frequencies (P < 0.001) of binucleated cells with micronuclei and total number of micronuclei in binucleated lymphocytes in comparison with subjects of the control group. A decrease (P < 0.001) in cytokinesis block proliferation index similarly demonstrates a genotoxic effect due to pesticide exposure. The results indicate that the pesticide industry workers have experienced significant genotoxic exposure. This study highlights the risk to workers in the pesticide manufacturing industries of developing countries such as Pakistan and the need for implementation of suitable safety measures to prevent/limit exposure to harmful toxins.

  9. Comparative hepatotoxicity and clastogenicity of sodium arsenite and three petroleum products in experimental Swiss Albino Mice: the modulatory effects of Aloe vera gel.

    PubMed

    Gbadegesin, Michael A; Odunola, Oyeronke A; Akinwumi, Kazeem A; Osifeso, Olabode O

    2009-10-01

    Petroleum products (PPs) consist of complex chemical mixtures, mainly hydrocarbons. Their composition varies considerably with source and use. Inappropriate manual handling and use of PPs, in countries like Nigeria, results in excessive skin contact with the possibility of hazard to health. There has been inadequate evidence to classify diesel, kerosene and hydraulic oil as human carcinogens and there is limited evidence for their toxicity and carcinogenicity in experimental animals. We compared the hepatotoxicity and clastogenicity of diesel, petrol or hydraulic oil with that of sodium arsenite (Na(2)AsO(2)) in mice. Our findings showed that these PPs are capable of inducing gamma-glutamyl transferase (gammaGT) activity in the serum and liver to levels comparable with that induced by Na(2)AsO(2). Mice treated with individual PPs have elevated mean liver and serum gammaGT at levels that are significantly different from the values observed for the negative control group. Also, the individual PPs alone have micronuclei formation induction activity similar to Na(2)AsO(2). We found that treatment with Aloe vera gel before the PPs significantly reduced mean liver and serum gammaGT, and the mean number of micronuclei scored when compared with groups administered each of the PPs alone, supporting the presence of hepatoprotective components in Aloe vera.

  10. Effect of Processing, Post-Harvest Irradiation, and Production System on the Cytotoxicity and Mutagenicity of Vitis labrusca L. Juices in HTC Cells

    PubMed Central

    Düsman, Elisângela; de Almeida, Igor Vivian; Lucchetta, Luciano; Vicentini, Veronica Elisa Pimenta

    2014-01-01

    The juices of grapes (Vitis labrusca L.) are similar to the fruit itself because the main constituents of the fruit are present in the juice. However, their quality characteristics may be modified by the harsh technological processes used for the production of integral food, such as production systems of raw materials and post-harvest treatment of grapes with ultraviolet (UV) irradiation. Therefore, the present study analyzed juices produced naturally (by liquefying the fruit) or by the technological process of extraction by steam distillation (90°C) of grapes from organic and conventional production systems that were untreated or treated with UV type C (65.6 J/m2 for 10 minutes). Using cultures of Rattus norvegicus hepatoma cells (HTC) in vitro, cytotoxic effects were assayed by the MTT test and by calculating the cytokinesis blocked proliferation index (CBPI), and mutagenic effects were measured by the cytokinesis block micronucleus assay. The results of the MTT assay and the CBPIs indicated that none of the juices were cytotoxic, including those that induced cell proliferation. The results of the micronucleus assay showed that none of the juices were mutagenic. However, the average number of micronuclei was lower in the juices produced from organic grapes, and cell proliferation, soluble acids and phenolic compounds were significantly higher. Compared with the natural juices, the integral juices of conventional grapes showed a higher average number of micronuclei as well as lower stimulation of cell proliferation and lower levels of bioactive compounds. The results demonstrate a beneficial effect of UV-C irradiation of post-harvest grapes in stimulating the synthesis of nutraceutical compounds without generating cytotoxic or mutagenic substances. Taken together, our findings support the consumption of grape juice and the application of food production techniques that enhance its nutritional value and promote its production, marketing and consumption. PMID

  11. Effect of processing, post-harvest irradiation, and production system on the cytotoxicity and mutagenicity of Vitis labrusca L. juices in HTC cells.

    PubMed

    Düsman, Elisângela; de Almeida, Igor Vivian; Lucchetta, Luciano; Vicentini, Veronica Elisa Pimenta

    2014-01-01

    The juices of grapes (Vitis labrusca L.) are similar to the fruit itself because the main constituents of the fruit are present in the juice. However, their quality characteristics may be modified by the harsh technological processes used for the production of integral food, such as production systems of raw materials and post-harvest treatment of grapes with ultraviolet (UV) irradiation. Therefore, the present study analyzed juices produced naturally (by liquefying the fruit) or by the technological process of extraction by steam distillation (90°C) of grapes from organic and conventional production systems that were untreated or treated with UV type C (65.6 J/m² for 10 minutes). Using cultures of Rattus norvegicus hepatoma cells (HTC) in vitro, cytotoxic effects were assayed by the MTT test and by calculating the cytokinesis blocked proliferation index (CBPI), and mutagenic effects were measured by the cytokinesis block micronucleus assay. The results of the MTT assay and the CBPIs indicated that none of the juices were cytotoxic, including those that induced cell proliferation. The results of the micronucleus assay showed that none of the juices were mutagenic. However, the average number of micronuclei was lower in the juices produced from organic grapes, and cell proliferation, soluble acids and phenolic compounds were significantly higher. Compared with the natural juices, the integral juices of conventional grapes showed a higher average number of micronuclei as well as lower stimulation of cell proliferation and lower levels of bioactive compounds. The results demonstrate a beneficial effect of UV-C irradiation of post-harvest grapes in stimulating the synthesis of nutraceutical compounds without generating cytotoxic or mutagenic substances. Taken together, our findings support the consumption of grape juice and the application of food production techniques that enhance its nutritional value and promote its production, marketing and consumption.

  12. Genomic damage in end-stage renal failure: potential involvement of advanced glycation end products and carbonyl stress.

    PubMed

    Stopper, Helga; Schupp, Nicole; Bahner, Udo; Sebekova, Katarina; Klassen, Andre; Heidland, August

    2004-09-01

    In patients with chronic renal failure, genomic damage has been shown by numerous biomarkers, such as micronuclei frequency and comet assay (single-cell gel electrophoresis) in peripheral lymphocytes, 8-hydroxy 2'-deoxyguanosine (8-OH-dG) content in leukocytes, mitochondrial DNA deletions in skeletal muscle tissue and hair follicles, as well as in DNA repair mechanisms in freshly isolated lymphocytes after ultraviolet light exposure. In the pathogenesis of DNA damage--besides genetic influences, enhanced reactive oxygen species (ROS), and lipid peroxidation-the genotoxic potential of advanced glycation end products (AGEs) and reactive carbonyl compounds deserve special attention. In fact, reactions of glucose with DNA can lead to mutagenic DNA AGEs. In vitro, incubation of tubulus cells with various AGEs and methylglyoxal induces DNA damage, which is suppressed by antioxidants. This underlines the role played by oxidative stress in DNA damage.

  13. Study on the genotoxicity of 13 mild coal gasification products

    SciTech Connect

    Zhong, B.Z.; Robbins, S.; Bryant, D.; Ong, T.; Ma, J.

    1994-12-31

    Mild gasification of coal is a technology being developed by the United States Department of Energy and private industry with the hope that a cleaner use of coal can help meet future energy needs. The mutagenicity of 13 gasification product samples from various coal mine sources, with different processing conditions and boiling point ranges, was studied using bacteria. The results show that 9 of the 13 composite samples displayed mutagenic activity in the Ames assay. Six mutagenic samples were further fractionated into basic, acidic nonpolar and polar neutral subfractions. All samples displayed mutagenic activity in the Ames assay with S9 in the nonpolar neutral subfraction. Five mutagenic samples were also tested for genotoxicity in three mammalian cell assays. None of the samples tested caused gene mutations in Chinese hamster lung fibroblast (V79) cells in the HGPRT assay system. However, all five samples were found to induce micronuclei and sister chromatid exchange in V79 cells. Chemical characterization of the subfractions indicates that the nonpolar neutral subfractions contain aromatic hydrocarbons. These compounds may be responsible for the genotoxic activity of samples.

  14. Repairing effects of interleukin 11 (IL-11) towards high dose methotrexate-induced rat small intestinal mucositis and its impacts on T-lymphoblastic leukemia cell line

    PubMed Central

    Han, Yueqin; Zhu, Yanping; Wang, Jinshen; Han, Yanqin; Qin, Daogang; Yang, Qiaozhi; Sun, Xiaojing; Chen, Lijun

    2016-01-01

    Objective(s): To investigate the efficacy of interleukin 11 (IL-11) towards the high dose methotrexate (HDMTX)-concurrent rat small intestinal mucositis and its impacts on the proliferation of the human T-lymphoblastic leukemia (CEM) cell line. Materials and Methods: 95 Wistar rats were randomly divided into five groups, the normal control group (A), the methotrexate (MTX) control group (B), the IL-11-pre-treated high-dose group (C), the post-IL-11-treatment high-dose group (D) and the post-IL-11-treatment low-dose group (E). After the intraperitoneal injection of MTX in the groups B-E, the rats were sacrificed at 1, 3, 5 and 7 days. The mortality, morphological and ultrastructural changes of small intestine of each group were observed. The cells were then cultured in vitro, and the MTT method was used to investigate the effects of different concentration of IL-11 on CEM proliferation and also on HDMTX-induced mucositis. Results: IL-11 could reduce the intestinal histopathological score, increase the height of small intestinal villi, promote the proliferation of intestinal lacunar cells and reduce the mortality rate of rats. The IL-11 pre-treatment group exhibited the best efficacies, demonstrating significant difference with the control group (P<0.01). In addition, the proliferation of CEM was not promoted, indicating that IL-11 could not inhibit HDMTX. Conclusion: IL-11 could reduce the severity of HDMTX-induced intestinal mucositis, and improve the survival rate of experimental rats, and could be safely used as the adjuvant treatment of HDMTX in childhood leukemia. PMID:27746864

  15. Repairing effects of interleukin 11 (IL-11) towards high dose methotrexate-induced rat small intestinal mucositis and its impacts on T-lymphoblastic leukemia cell line

    PubMed Central

    Han, Yueqin; Zhu, Yanping; Wang, Jinshen; Han, Yanqin; Qin, Daogang; Yang, Qiaozhi; Sun, Xiaojing; Chen, Lijun

    2016-01-01

    Objective(s): To investigate the efficacy of interleukin 11 (IL-11) towards the high dose methotrexate (HDMTX)-concurrent rat small intestinal mucositis and its impacts on the proliferation of the human T-lymphoblastic leukemia (CEM) cell line. Materials and Methods: 95 Wistar rats were randomly divided into five groups, the normal control group (A), the methotrexate (MTX) control group (B), the IL-11-pre-treated high-dose group (C), the post-IL-11-treatment high-dose group (D) and the post-IL-11-treatment low-dose group (E). After the intraperitoneal injection of MTX in the groups B-E, the rats were sacrificed at 1, 3, 5 and 7 days. The mortality, morphological and ultrastructural changes of small intestine of each group were observed. The cells were then cultured in vitro, and the MTT method was used to investigate the effects of different concentration of IL-11 on CEM proliferation and also on HDMTX-induced mucositis. Results: IL-11 could reduce the intestinal histopathological score, increase the height of small intestinal villi, promote the proliferation of intestinal lacunar cells and reduce the mortality rate of rats. The IL-11 pre-treatment group exhibited the best efficacies, demonstrating significant difference with the control group (P<0.01). In addition, the proliferation of CEM was not promoted, indicating that IL-11 could not inhibit HDMTX. Conclusion: IL-11 could reduce the severity of HDMTX-induced intestinal mucositis, and improve the survival rate of experimental rats, and could be safely used as the adjuvant treatment of HDMTX in childhood leukemia[PARANDCO1]. PMID:27635197

  16. Tc-99 m diethylenetriamine-pentaacetic acid (DTPA): is it reliable for assessment of methotrexate-induced cumulative effect on renal filtration in rheumatoid arthritis patients?

    PubMed

    Amin, Amr; Effat, Dina; Goher, Nabila; Ramadan, Basma

    2013-12-01

    Methotrexate (MTX) is commonly employed as the initial DMARD used for the treatment of rheumatoid arthritis (RA). We aimed to contribute to the safety profile of MTX by assessing its cumulative effect on renal filtration. A total of 52 RA adult female patients with normal baseline serum creatinine and GFR at the initial diagnosis of the disease were included. Group 1 (G1) included 30 patients (mean age 40.4 ± 4.4 years) on MTX and NSAIDS, while 22 RA patients (mean age 38.5 ± 8.2 years) who received NSAIDs only served as control group (G2). Renal function was assessed by GFR measurement using technetium diethylenetriamine-pentaacetic acid (Tc-99 m DTPA) at a point of the study time corresponding to disease duration. Twenty-one out of thirty (70 %) in G1 showed reduced GFR compared to 6/22 (27.3 %) in G2 (P = 0.007), with 3.3 ± 0.5 % annual reduction in GFR. Reduced GFR in G1 showed significant negative correlation with age (r = -0.396, P = 0.005), MTX cumulative dose (r = -0.263, P = 0.049), MTX-intake duration (r = -0.293, P = 0.031) and NSAIDs-intake duration (r = -0.344, P = 0.014). Low-dose MTX has a slow cumulative effect on renal filtration manifested by GFR reduction overtime that could be monitored by Tc-99 m DTPA.

  17. In a methotrexate-induced model of intestinal mucositis, olmesartan reduced inflammation and induced enteropathy characterized by severe diarrhea, weight loss, and reduced sucrose activity.

    PubMed

    de Araújo, Aurigena Antunes; Borba, Pedro Brito; de Souza, Fernando Henrique Destefani; Nogueira, Anália Cristina; Saldanha, Taís Suassuna; Araújo, Thayse Emanuele Franklin; da Silva, Aldemara Ingrid; de Araújo Júnior, Raimundo Fernandes

    2015-01-01

    The aim of this study was to evaluate the effect of olmesartan (OLME), an angiotensin II receptor antagonist, on an intestinal mucositis model. Briefly, daily intraperitoneal (i.p.) injections of methotrexate (MTX) 7 mg/kg were administered to rats on 3 consecutive days. A subset of these rats was also pretreated with oral administration of OLME (0.5, 1.0, or 5.0 mg/kg) or vehicle as a control 30 min prior to MTX injection. Body weight, feces scoring, and death were recorded daily. On day 4, the rats were killed, and intestinal tissues were assayed for levels of interleukin (IL)-1β and tumor necrosis factor (TNF)-α, myeloperoxidase and sucrose activity, and histopathological findings. A significant reduction in body weight was observed in the MTX+1.0 mg/kg OLME group (p<0.01). The feces scores for the MTX+0.5 mg/kg OLME and MTX+5.0 mg/kg OLME groups were also significantly higher (p<0.001). Sucrose activity was reduced in all groups treated with OLME (p<0.05). Treatment with MTX+OLM at all doses resulted in reduced inflammatory infiltration, ulcerations, vasodilation, and hemorrhagic areas (p<0.05), as well as reduced concentrations of myeloperoxidase (p<0.001). The IL-1β and TNF-α levels were decreased in the MTX+OLME 5.0 mg/kg (p<0.01 and p<0.05, respectively) compared with the MTX-alone group. Overall, antiinflammatory activity was observed in rats with MTX-induced intestinal mucositis that were administered OLME. However, further studies are needed to elucidate the adverse effects of OLME.

  18. Methotrexate induces apoptosis through p53/p21-dependent pathway and increases E-cadherin expression through downregulation of HDAC/EZH2.

    PubMed

    Huang, Wen-Yu; Yang, Pei-Ming; Chang, Yu-Fan; Marquez, Victor E; Chen, Ching-Chow

    2011-02-15

    Methotrexate (MTX) is a dihydrofolate reductase (DHFR) inhibitor widely used as an anticancer drug in different kinds of human cancers. Here we investigated the anti-tumor mechanism of MTX against non-small cell lung cancer (NSCLC) A549 cells. MTX not only inhibited in vitro cell growth via induction of apoptosis, but also inhibited tumor formation in animal xenograft model. RNase protection assay (RPA) and RT-PCR demonstrated its induction of p53 target genes including DR5, p21, Puma and Noxa. Moreover, MTX promoted p53 phosphorylation at Ser15 and acetylaion at Lys373/382, which increase its stability and expression. The apoptosis and inhibition of cell viability induced by MTX were dependent on p53 and, partially, on p21. In addition, MTX also increased E-cadherin expression through inhibition of histone deacetylase (HDAC) activity and downregulation of polycomb group protein enhancer of zeste homologue 2 (EZH2). Therefore, the anticancer mechanism of MTX acts through initiation of p53-dependent apoptosis and restoration of E-cadherin expression by downregulation of HDAC/EZH2.

  19. Acute methotrexate-induced encephalopathy--causal relation to homozygous allelic state for MTR c.2756A>G (D919G)?

    PubMed

    Linnebank, M; Malessa, S; Moskau, S; Semmler, A; Pels, H; Klockgether, T; Schlegel, U

    2007-08-01

    Methotrexate (MTX) is widely used in the treatment of hematological diseases. The typical side-effects of high-dose MTX chemotherapy on the CNS range from asymptomatic white matter changes to severe CNS demyelination. MTX neuro - toxicity has been described to be associated with homocysteine and folate levels as well as genetic variants affecting methionine metabolism. Here we describe a case of severe, acute MTX-induced encephalopathy in a patient who was found to be homozygous for the rare missense variant methionine synthase (MTR) c.2756A>G (D919G), which may have modified the effect of MTX on homocysteine metabolism. This finding encourages further studies to determine to what extent the individual conditions of folate and methionine metabolism influence the effects or side-effects of MTX treatment.

  20. Association of genetic variants of methionine metabolism with methotrexate-induced CNS white matter changes in patients with primary CNS lymphoma.

    PubMed

    Linnebank, Michael; Moskau, Susanna; Jürgens, Annika; Simon, Matthias; Semmler, Alexander; Orlopp, Katjana; Glasmacher, Axel; Bangard, Christopher; Vogt-Schaden, Marlies; Urbach, Horst; Schmidt-Wolf, Ingo G H; Pels, Hendrik; Schlegel, Uwe

    2009-02-01

    Methotrexate (MTX) is an important anticancer drug and the most efficient chemotherapy component in primary CNS lymphoma (PCNSL). A typical side effect of intravenous high-dose MTX is the occurrence of confluent CNS white matter changes (WMC). Because MTX directly interferes with methionine metabolism, we analyzed the impact of genetic variants of methionine metabolism on the occurrence of WMC as a model of MTX toxicity. In a retrospective analysis of 68 PCNSL patients treated with MTX-based polychemotherapy with (n = 42) or without (n = 26) intraventricular treatment, 10 genetic variants influencing methionine metabolism were analyzed. Pearson's chi(2) test and multinominal regression analysis were used to define the relevance of these genetic variants for the occurrence of WMC. In this patient sample, the occurrence of WMC was significantly predicted by the TT genotype of methylenetetrahydrofolate reductase c.677C>T (chi(2) = 8.67; p = 0.013; df = 2), the AA genotype of methylenetetrahydrofolate reductase c.1298A>C (chi(2) = 13.5; p = 0.001; df = 2), and the GG genotype of transcobalamin 2 c.776C>G (chi(2) = 19.73; p < 0.001), in addition to male gender (chi(2) = 11.95; p = 0.001). These data strengthen the hypothesis that MTX effects are influenced by methionine metabolism, which may offer new strategies to improve MTX-based therapies.

  1. The protective role of G protein-coupled estrogen receptor 1 (GPER-1) on methotrexate-induced nephrotoxicity in human renal epithelium cells.

    PubMed

    Kurt, Akif Hakan; Bozkus, Fulsen; Uremis, Nuray; Uremis, Muhammed Mehdi

    2016-06-01

    Nephrotoxicity is an important problem during methotrexate (MTX) treatment, which has been widely used for the treatment of several cancer types. Females are less susceptible to kidney diseases; however, the reason for this condition has not to be fully clarified. But sex hormones such as estrogen may have a protective effect on the kidney. We aimed to evaluate the possible protective role of estrogen on the MTX-induced renal epithelial cell death. Primary renal proximal tubular epithelial cells (RPTEC) were incubated with MTX (1, 10 and 100 μM), either alone or in combination with the 17β-estradiol, G protein-coupled estrogen receptor 1 (GPER1) agonist G-1, estrogen receptor alpha agonist propyl pyrazole triol (PPT), estrogen receptor beta agonist diarylpropionitrile (DPN). Cell viability was determined by MTT assays. Interleukin (IL)-1β, IL-6, superoxide dismutase (SOD) and malondialdehyde (MDA) levels were determined in RPTEC. Approximately half of the cell death was observed with 10 μM MTX incubation for 48 h. The cell death was prevented by co-incubating with17β-estradiol, PPT and G-1. MTX was significantly induced IL-1β and IL-6.17β-estradiol, PPT and G-1 significantly decreased effects of MTX. SOD activity was significantly decreased treatment with MTX compared to control group. SOD activity was increased with co-incubation with 17β-estradioland G-1 compared to treatment with MTX. MDA levels significantly increased in treatment with MTX compared with the control group. Increased MDA levels by MTX-induced was decreased significantly by the treatment with 17β-estradiol and G-1. These data indicate that especially 17β-estradiol and G-1 may be useful in preventing undesirable effects of MTX in renal failure.

  2. ω-3 fatty acids as an adjuvant therapy ameliorates methotrexate-induced hepatotoxicity in children and adolescents with acute lymphoblastic leukemia: A randomized placebo-controlled study.

    PubMed

    Elbarbary, Nancy Samir; Ismail, Eman Abdel Rahman; Farahat, Reham Kamel; El-Hamamsy, Manal

    2016-01-01

    Methotrexate (MTX)-induced hepatotoxicity is a significant clinical problem that may affect overall prognosis and disease outcome. Oxidative stress is a key player in its pathogenesis. The aim of this study was to investigate the role of ω-3 fatty acids as an adjuvant therapy in children and adolescents with acute lymphoblastic leukemia (ALL) during the maintenance phase of chemotherapy and the effect of ω-3 on MTX-induced hepatotoxicity. This randomized, double-blind, placebo-controlled trial included 70 patients with ALL who were in the maintenance phase. The participants were divided into two groups: group A received oral MTX and ω-3 fatty acids (1000 mg/d) and group B (received MTX and placebo). Both groups were followed-up for 6 mo with assessment of liver enzymes, total antioxidant capacity (TAC), uric acid, malondialdhyde, superoxide dismutase (SOD), and glutathione peroxidase. The trial was registered at ClinicalTrials.gov (NCT02373579). Baseline clinical and laboratory parameters were consistent between the two groups (P > 0.05). After 6 mo, liver enzymes and malondialdhyde increased, whereas TAC, uric acid, SOD, and glutathione peroxidase decreased in group B (MTX and placebo) compared with baseline levels or with group A ALL patients receiving ω-3 fatty acids (P < 0.001). The addition of ω-3 to MTX maintained normal liver function and oxidant-antioxidant levels among group A patients at the end of treatment compared with pretherapy levels (P > 0.05). No adverse reactions due to ω-3 supplementation were reported. ALT was inversely correlated to TAC and SOD in the MTX group. The study determined that ω-3 fatty acids ameliorated MTX-induced hepatotoxicity and could be safely used during the maintenance phase of ALL. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. The role of the MTHFR 677C>T polymorphism in methotrexate-induced liver toxicity: a meta-analysis in patients with cancer.

    PubMed

    Hagleitner, M M; Coenen, M J H; Aplenc, R; Patiño-Garcia, A; Chiusolo, P; Gemmati, D; De Mattei, M; Ongaro, A; Krajinovic, M; Hoogerbrugge, P M; Vermeulen, S H H M; te Loo, D M W M

    2014-04-01

    Methotrexate (MTX), one of the important pillars in the treatment of different forms of cancer, is associated with the development of hepatotoxicity. The 677C>T variant (rs1801133) in the methylenetetrahydrofolate reductase (MTHFR) gene might affect the development of hepatotoxicity. Results in literature are, however, contradictive. The aim of this study was to evaluate the role of the MTHFR 677C>T polymorphism in MTX-induced hepatotoxicity by analyzing a Dutch cohort of pediatric patients treated with high doses of MTX and subsequently performing a meta-analysis. Ninety-eight patients receiving 542 courses of high-dose MTX were genotyped for the MTHFR 677C>T variant. Hepatotoxicity was evaluated retrospectively according to common terminology criteria for adverse events-National Cancer Institute criteria. The influence of MTHFR 677C>T on hepatotoxicity was examined using a generalized estimating equation (GEE) analysis. A fixed-effect meta-analysis based on this and previous studies investigating the association between the MTHFR 677C>T polymorphism and uniformly coded hepatotoxicity was performed. The GEE analysis showed an increased risk of developing hepatotoxicity for T versus C allele (odds ratio (OR) 1.8; 95% confidence interval (CI) 1.0-3.2, P=0.04). This finding was not supported by the meta-analysis including seven studies and 1044 patients; the OR for the 677T versus C allele was 1.1 (95% CI 0.84-1.5, P=0.25). Heterogeneity between studies was observed, possibly related to differences in MTX dose and leucovorin rescue. In conclusion, in patients with cancer, the MTHFR 677T allele has only a minor role in the development of MTX-induced hepatotoxicity. Observed heterogeneity between studies warrants further study into (tailored) leucovorin rescue.

  4. Genotoxicity of imidacloprid in relation to metabolic activation and composition of the commercial product.

    PubMed

    Costa, C; Silvari, V; Melchini, A; Catania, S; Heffron, J J; Trovato, A; De Pasquale, R

    2009-01-01

    Imidacloprid is a neonicotinoid insecticide combining excellent efficiency against parasites with low toxicity for mammals. Commercially, it is co-formulated with dimethyl sulfoxide, methylpyrrolidone, propylene carbonate and mineral oil, which can modify its bioavailability and toxicological profile for humans following occupational exposure. A combined in vitro approach employing the comet assay and the micronucleus test was used to assess the genotoxicity of imidacloprid in relation to formulation, metabolic activation and exposure level. Human peripheral blood lymphocytes from unexposed healthy volunteers were treated with imidacloprid (0.2, 2 and 20 μM) and with equimolar concentrations of a commercial product, with and without addition of S9 fraction. Imidacloprid significantly increased the comet score and the frequency of micronuclei only at the highest concentration tested. DNA damage was slightly more severe with the commercial product, and was increased, though not significantly, by metabolic activation. Formation of reactive oxygen species (ROS) does not seem to be involved as a mechanism of genotoxicity, but this result may be explained by the insufficient sensitivity of the 2',7'-dichlorofluorescein diacetate assay at the test concentrations of imidacloprid. These results suggest that at concentrations<20 μM imidacloprid is not genotoxic to human lymphocytes in vitro. Nonetheless, the presence of co-formulants in the commercial product and occupational exposure, along with poor safety procedures, may present an increased risk for DNA fragmentation and chromosomal aberrations.

  5. Hydrogen production

    NASA Technical Reports Server (NTRS)

    England, C.; Chirivella, J. E.; Fujita, T.; Jeffe, R. E.; Lawson, D.; Manvi, R.

    1975-01-01

    The state of hydrogen production technology is evaluated. Specific areas discussed include: hydrogen production fossil fuels; coal gasification processes; electrolysis of water; thermochemical production of hydrogen; production of hydrogen by solar energy; and biological production of hydrogen. Supply options are considered along with costs of hydrogen production.

  6. Hydrogen production

    NASA Technical Reports Server (NTRS)

    England, C.; Chirivella, J. E.; Fujita, T.; Jeffe, R. E.; Lawson, D.; Manvi, R.

    1975-01-01

    The state of hydrogen production technology is evaluated. Specific areas discussed include: hydrogen production fossil fuels; coal gasification processes; electrolysis of water; thermochemical production of hydrogen; production of hydrogen by solar energy; and biological production of hydrogen. Supply options are considered along with costs of hydrogen production.

  7. Sequential fractionation with concurrent chemical and toxicological characterization of the combustion products of chlorogenic acid.

    PubMed

    Kaur, Navneet; Lacasse, Martine; Fürtös, Alexandra; Waldron, Karen C; Morin, André

    2009-06-05

    Chlorogenic acid is the most abundant polyphenol found in the tobacco plant. The biological effects of its combustion products remain largely unknown. In this study, chlorogenic acid was burned at 640 degrees C for 2 min and the particulate matter of the smoke was collected onto Cambridge filter pads followed by selective extraction in five different solvents. Various fractions of the chlorogenic acid combustion products were tested for induction of micronuclei in V79 Chinese hamster fibroblast cells. Over 40 compounds were identified in the dimethyl sulfoxide (DMSO) extract by high-performance liquid chromatography coupled to electrospray time-of-flight mass spectrometry (HPLC/TOF-MS). The DMSO extract was then fractionated into three major fractions by preparative LC. The fraction inducing the highest degree of toxicity was further separated into four sub-fractions. The sub-fraction responsible for the most toxic response was determined to contain catechol as its major component. The overall reproducibility of the combustion, the extraction procedure and the chemical characterization of the compounds responsible for the toxicity in the chlorogenic acid smoke were evaluated by LC/TOF-MS.

  8. RENEB intercomparison exercises analyzing micronuclei (Cytokinesis-block Micronucleus Assay).

    PubMed

    Depuydt, Julie; Baeyens, Ans; Barnard, Stephen; Beinke, Christina; Benedek, Anett; Beukes, Philip; Buraczewska, Iwona; Darroudi, Firouz; De Sanctis, Stefania; Dominguez, Inmaculada; Monteiro Gil, Octávia; Hadjidekova, Valeria; Kis, Enikő; Kulka, Ulrike; Lista, Florigio; Lumniczky, Katalin; M'kacher, Radhia; Moquet, Jayne; Obreja, Doina; Oestreicher, Ursula; Pajic, Jelena; Pastor, Nuria; Popova, Ljubomira; Regalbuto, Elisa; Ricoul, Michelle; Sabatier, Laure; Slabbert, Jacobus; Sommer, Sylwester; Testa, Antonella; Thierens, Hubert; Wojcik, Andrzej; Vral, Anne

    2017-01-01

    In the framework of the 'Realizing the European Network of Biodosimetry' (RENEB) project, two intercomparison exercises were conducted to assess the suitability of an optimized version of the cytokinesis-block micronucleus assay, and to evaluate the capacity of a large laboratory network performing biodosimetry for radiation emergency triages. Twelve European institutions participated in the first exercise, and four non-RENEB labs were added in the second one. Irradiated blood samples were shipped to participating labs, whose task was to culture these samples and provide a blind dose estimate. Micronucleus analysis was performed by automated, semi-automated and manual procedures. The dose estimates provided by network laboratories were in good agreement with true administered doses. The most accurate estimates were reported for low dose points (≤ 0.94 Gy). For higher dose points (≥ 2.7 Gy) a larger variation in estimates was observed, though in the second exercise the number of acceptable estimates increased satisfactorily. Higher accuracy was achieved with the semi-automated method. The results of the two exercises performed by our network demonstrate that the micronucleus assay is a useful tool for large-scale radiation emergencies, and can be successfully implemented within a large network of laboratories.

  9. Micronuclei in epithelial cells from sputum of uranium workers

    SciTech Connect

    Loomis, D.P.; Shy, C.M.; Allen, J.W.; Saccomanno, G.

    1990-01-01

    The exfoliated-cell micronucleus (MN) assay was used to assess cytogenetic effects of exposure to radon progeny and cigarette smoke among 99 Colorado plateau uranium workers. Subjects were selected at random from employees in underground and open-pit uranium mines, ore mills, laboratories, and offices participating in a sputum screening program from 1964-88. The prevalence of cells with MN was determined by scoring one sputum specimen for each worker. Data obtained by interview were used to classify exposure to radon progeny and smoking at the time sputum specimens were taken. Underground miners were considered exposed to radon progeny, and others were considered unexposed. Neither radon progeny exposure nor cigarette smoking had any appreciable effect on the prevalence of cells with MN; crude prevalence ratios were 1.0 (95% CI 0.7-1.4) and 0.9 (95% CE 0.6-1.3), respectively. The effects of radon and smoking were not confounded by each other or by age, and there was no evidence of synergy between exposures. The findings appear to cast doubt on the epidemiological utility of a sputum-based MN assay for studies of other populations exposed to occupational or environmental lung carcinogens.

  10. Effect of drinking water disinfection by-products in human peripheral blood lymphocytes and sperm.

    PubMed

    Ali, Aftab; Kurzawa-Zegota, Malgorzata; Najafzadeh, Mojgan; Gopalan, Rajendran C; Plewa, Michael J; Anderson, Diana

    2014-12-01

    Drinking water disinfection by-products (DBPs) are generated by the chemical disinfection of water and may pose hazards to public health. Two major classes of DBPs are found in finished drinking water: haloacetic acids (HAAs) and trihalomethanes (THMs). HAAs are formed following disinfection with chlorine, which reacts with iodide and bromide in the water. Previously the HAAs were shown to be cytotoxic, genotoxic, mutagenic, teratogenic and carcinogenic. To determine the effect of HAAs in human somatic and germ cells and whether oxidative stress is involved in genotoxic action. In the present study both somatic and germ cells have been examined as peripheral blood lymphocytes and sperm. The effects of three HAA compounds: iodoacetic acid (IAA), bromoacetic acid (BAA) and chloroacetic acid (CAA) were investigated. After determining appropriate concentration responses, oxygen radical involvement with the antioxidants, butylated hydroxanisole (BHA) and the enzyme catalase, were investigated in the single cell gel electrophoresis (Comet) assay under alkaline conditions, >pH 13 and the micronucleus assay. In the Comet assay, BHA and catalase were able to reduce DNA damage in each cell type compared to HAA alone. In the micronucleus assay, micronuclei (MNi) were found in peripheral lymphocytes exposed to all three HAAs and catalase and BHA were in general, able to reduce MNi induction, suggesting oxygen radicals play a role in both assays. These observations are of concern to public health since both human somatic and germ cells show similar genotoxic responses. Copyright © 2014. Published by Elsevier B.V.

  11. Red mud a byproduct of aluminum production contains soluble vanadium that causes genotoxic and cytotoxic effects in higher plants.

    PubMed

    Mišík, Miroslav; Burke, Ian T; Reismüller, Matthias; Pichler, Clemens; Rainer, Bernhard; Mišíková, Katarina; Mayes, William M; Knasmueller, Siegfried

    2014-09-15

    Red mud (RM) is a byproduct of aluminum production; worldwide between 70 and 120 million tons is produced annually. We analyzed RM which was released in the course of the Kolontar disaster in Hungary into the environment in acute and genotoxicity experiments with plants which are widely used for environmental monitoring. We detected induction of micronuclei which reflect chromosomal damage in tetrads of Tradescantia and in root cells of Allium as well as retardation of root growth with contaminated soils and leachates. Chemical analyses showed that RM contains metals, in particular high concentrations of vanadium. Follow-up experiments indicated that vanadate causes the effects in the plants. This compound causes also in humans DNA damage and positive results were obtained in carcinogenicity studies. Since it was found also in RM from other production sites our findings indicate that its release in the environment is a global problem which should be studied in more detail. Our findings indicate that the red mud causes genotoxic effect in plants probably due to the presence of vanadate which is contained at high concentrations in the residue. Copyright © 2014. Published by Elsevier B.V.

  12. Chromosome elimination and in vivo haploid production induced by Stock 6-derived inducer line in maize (Zea mays L.).

    PubMed

    Zhang, Zili; Qiu, Fazhan; Liu, Yongzhong; Ma, Kejun; Li, Zaiyun; Xu, Shangzhong

    2008-12-01

    In vivo haploid production induced by inducer lines derived from Stock 6 is widely used in breeding program of maize (Zea mays L.), but the mechanisms behind have not yet been fully understood. In this study, average frequency of haploid induction in four inbred lines by Stock 6-derived inducer line HZI1 was above 10%. About 0.2% kernels from the cross Hua24 x HZI1 had mosaic endosperm showing yellow shrunken parts from Hua24 to normal parts with purple aleurone from HZI1. Individual lagged chromosomes and micronuclei were observed in mitotic cells of ovules pollinated by HZI1. Above 56.4% of the radicles from the kernels with purple aleurone and colorless embryos were mixoploid (2n = 9-21), and more than 45.22% cells were haploid cells (2n = 10) in three crosses. More than 62.5% of the radicles from the kernels with purple aleurone and purple embryos were mixoploid (2n = 9-21) having 54.27% cells with 2n = 20. SSR analysis showed that all haploids from the cross Hua24 x HZI1 shared the same genomic compositions as Hua24 except for plants Nos. 862 and 857 with some polymorphic DNA bands. The results revealed that chromosome elimination after fertilization caused the haploid production in maize.

  13. Antihydrogen production

    SciTech Connect

    Rizzini, Evandro Lodi; Venturelli, Luca; Zurlo, Nicola

    2008-08-08

    Antihydrogen production in ATHENA is analyzed more carefully. The most important peculiarities of the different experimental situations are discussed. The protonium production via the first matter-antimatter chemical reaction is commented too.

  14. Production plunger

    SciTech Connect

    Krueger, W.E.

    1989-12-26

    This patent describes a production plunger for reciprocating in the production string of wells that produce both liquid and gas to assist the gas in lifting produced liquid to the surface. It comprises: a body for reciprocating in the production string of a well. The body having a passageway extending longitudinally through the body, and means closing the lower end of the passageway, seal means carried by the body for engaging the inner wall of the production string to prevent fluid flowing upwardly in the production string from passing between the body and the inner wall of the production string, a valve seat in the passageway, a valve member located in the passageway in the body above the valve seat, a valve rod connected to the valve member and extending downwardly through the valve seat, and a piston connected to the valve rod below the valve seat.

  15. Swine production.

    PubMed

    Plain, Ronald L; Lawrence, John D

    2003-07-01

    The US swine industry is large and growing. The quantity of pork desired by consumers of US pork is growing at the rate of 1.5%/y. New production systems and new technology have enabled production per sow to grow at a rate of 4% annually in recent years. Consequently, the number of sows in the United States is declining. Because productivity growth is outpacing demand growth, the deflated price of hogs and pork is declining. Hog production and prices continue to exhibit strong seasonal and cyclic patterns. Pork production is usually lowest in the summer and highest in the fall. Production and prices tend to follow 4-year patterns. The US swine industry continues to evolve toward fewer and larger producers who rely on contracts for both hog production and marketing. In 2000, over half of the hogs marketed were from approximately 156 firms marketing more than 50,000 head annually. These producers finished 60% of their production in contract facilities. Over 90% of their marketings were under contract or were owned by a packer. These producers expressed a high level of satisfaction with hog production. Both they and their contract growers were satisfied with production contracts. These large producers were satisfied with their marketing contracts and planned to continue them in the future. The hog industry has changed a great deal in the last decade. There is little reason to believe this rapid rate of change will not continue. This swine industry is highly competitive and profit driven. Profit margins are too small to allow producers the luxury of ignoring new technology and innovative production systems. Consequently, hog production will continue its rapid evolution from traditional agriculture to typical industry.

  16. Hydrogen Production

    SciTech Connect

    2014-09-01

    This 2-page fact sheet provides a brief introduction to hydrogen production technologies. Intended for a non-technical audience, it explains how different resources and processes can be used to produce hydrogen. It includes an overview of research goals as well as “quick facts” about hydrogen energy resources and production technologies.

  17. Managing Productivity.

    DTIC Science & Technology

    1985-01-01

    Productivity Impediments 3 Cause One 3 Cause Two 4 Cause Three 4 Cause Four 5 Cause Five 6 3. Motivation And Productivity 7 Maslow’s Hierarchy of Needs 7...motivation theory car be traced through the teachings of Abraham Maslow, Doug’as McGregor, and Frederick Hertzberg: Maslow’s Hierarchy Of Needs In his book

  18. University Productivity

    ERIC Educational Resources Information Center

    Sommers, Alexis N.

    1977-01-01

    Academic communities are under intense pressures to balance expenditures with income. Strategies are offered here to increase productivity drawn from the experiences of the University of New Haven. Emphasis is on revenue-cost ratios, class size, and faculty teaching schedules as primary factors in productivity improvement. (Editor/LBH)

  19. Household Production.

    ERIC Educational Resources Information Center

    Scholl, Kathleen K.; And Others

    1982-01-01

    Compiled to give readers information on current research in household production, this special issue focuses on the family as a provider of goods and services. It includes five feature articles, a summary of a survey of American farm women, and a brief analysis of sources of time-use data for estimating the value of household production. Covered…

  20. Genotoxicity of Advanced Glycation End Products: Involvement of Oxidative Stress and of Angiotensin II Type 1 Receptors

    NASA Astrophysics Data System (ADS)

    Schupp, Nicole; Schinzel, Reinhard; Heidland, August; Stopper, Helga

    2005-06-01

    In patients with chronic renal failure, cancer incidence is increased. This may be related to an elevated level of genomic damage, which has been demonstrated by micronuclei formation as well as by comet assay analysis. Advanced glycation end products (AGEs) are markedly elevated in renal failure. In the comet assay, the model AGEs methylglyoxal- and carboxy(methyl)lysine-modified bovine serum albumin (BSA) induced significant DNA damage in colon, kidney, and liver cells. The addition of antioxidants prevented AGE-induced DNA damage, suggesting enhanced formation of reactive oxygen species (ROS). The coincubation with dimethylfumarate (DMF), an inhibitor of NF-κB translocation, reduced the genotoxic effect, thereby underscoring the key role of NF-κB in this process. One of the genes induced by NF-κB is angiotensinogen. The ensuing proteolytic activity yields angiotensin II, which evokes oxidative stress as well as proinflammatory responses. A modulator of the renin-angiotensin system (RAS), the angiotensin II (Ang II) receptor 1 antagonist, candesartan, yielded a reduction of the AGE-induced DNA damage, connecting the two signal pathways, RAS and AGE signaling. We were able to identify important participants in AGE-induced DNA damage: ROS, NF-κB, and Ang II, as well as modulators to prevent this DNA damage: antioxidants, DMF, and AT1 antagonists.

  1. Exposure to lambda-cyhalothrin, a synthetic pyrethroid, increases reactive oxygen species production and induces genotoxicity in rat peripheral blood.

    PubMed

    Fetoui, Hamadi; Feki, Ameni; Salah, Ghada Ben; Kamoun, Hassen; Fakhfakh, Feiza; Gdoura, Radhouane

    2015-05-01

    Lambda-cyhalothrin (LTC) is a synthetic pyrethroid with a broad spectrum of insecticidal and acaricidal activities used to control a wide range of insect pests in a variety of applications. However, there is little known about its adverse effects, in particular those related to its genotoxicity in humans. To elucidate the genotoxicity mechanisms of LTC, the micronuclei (MN) frequencies, the levels of reactive oxygen species (ROS), erythrocyte osmotic fragility, nitrite (NO) formation, protein carbonyl (PCO) levels and malondialdehyde (MDA) production were evaluated for a period of 7, 14 and 21 days. Our results show that exposure rat to LTC (1/10DL50 = 6.23 mg/kg) for a period of 7, 14 and 21 days induced a noticeable genotoxic effect in rat peripheral blood evidenced by a significant increase in the frequency of MN only at day 21 of treatment. Significant differences between the two groups were observed in erythrocyte osmotic fragility. Further, a significant (p < 0.01) increase in ROS contents, NO formation, PCO levels and lipid peroxidation in erythrocytes were observed at different times of treatments, suggesting the implication of oxidative stress in its toxicity. These results confirm the genotoxic and the pro-oxidant effects of LTC in rat peripheral blood. © The Author(s) 2013.

  2. Quarkonium production

    SciTech Connect

    Arnd Meyer

    2001-03-28

    Results on the production of heavy Quarkonia ({psi} and {Upsilon} families) from the HERA and Tevatron colliders are presented. The interpretation of the measurements in terms of perturbative QCD is critically reviewed.

  3. Cordless Products

    NASA Technical Reports Server (NTRS)

    2001-01-01

    Apollo-era technology spurred the development of cordless products that we take for granted everyday. In the 1960s, NASA asked Black Decker to develop a special drill that would be powerful enough to cut through hard layers of the lunar surface and be lightweight, compact, and operate under its own power source, allowing Apollo astronauts to collect lunar samples further away from the Lunar Experiment Module. In response, Black Decker developed a computer program that analyzed and optimized drill motor operations. From their analysis, engineers were able to design a motor that was powerful yet required minimal battery power to operate. Since those first days of cordless products, Black Decker has continued to refine this technology and they now sell their rechargeable products worldwide (i.e. the Dustbuster, cordless tools for home and industrial use, and medical tools.)

  4. Bottom production

    SciTech Connect

    Baines, J.; Baranov, S.P.; Bartalini, P.; Bay, A.; Bouhova, E.; Cacciari, M.; Caner, A.; Coadou, Y.; Corti, G.; Damet, J.; Dell-Orso, R.; De Mello Neto, J.R.T.; Domenech, J.L.; Drollinger, V.; Eerola, P.; Ellis, N.; Epp, B.; Frixione, S.; Gadomski, S.; Gavrilenko, I.; Gennai, S.; George, S.; Ghete, V.M.; Guy, L.; Hasegawa, Y.; Iengo, P.; Jacholkowska, A.; Jones, R.; Kharchilava, A.; Kneringer, E.; Koppenburg, P.; Korsmo, H.; Kramer, M.; Labanca, N.; Lehto, M.; Maltoni, F.; Mangano, M.L.; Mele, S.; Nairz, A.M.; Nakada, T.; Nikitin, N.; Nisati, A.; Norrbin, E.; Palla, F.; Rizatdinova, F.; Robins, S.; Rousseau, D.; Sanchis-Lozano, M.A.; Shapiro, M.; Sherwood, P.; Smirnova, L.; Smizanska, M.; Starodumov, A.; Stepanov, N.; Vogt, R.

    2000-03-15

    In the context of the LHC experiments, the physics of bottom flavoured hadrons enters in different contexts. It can be used for QCD tests, it affects the possibilities of B decays studies, and it is an important source of background for several processes of interest. The physics of b production at hadron colliders has a rather long story, dating back to its first observation in the UA1 experiment. Subsequently, b production has been studied at the Tevatron. Besides the transverse momentum spectrum of a single b, it has also become possible, in recent time, to study correlations in the production characteristics of the b and the b. At the LHC new opportunities will be offered by the high statistics and the high energy reach. One expects to be able to study the transverse momentum spectrum at higher transverse momenta, and also to exploit the large statistics to perform more accurate studies of correlations.

  5. Transplant production

    USDA-ARS?s Scientific Manuscript database

    For field pepper (Capsicum spp.) production, plants can be established from direct seed or transplants depending on the location and cultural practices for the specific pepper type grown. Direct seeding can result in slow, variable, and reduced plant stands due to variations in soil temperature, wat...

  6. Novolak Production

    NASA Astrophysics Data System (ADS)

    Aiba, Hiroshi

    Novolak resins are produced by reacting formaldehyde (30-55% concentration) with phenol under acidic conditions, with oxalic acid as the preferred catalyst and in special conditions, sulfuric acid. Depending on the batch size, all raw material components can be introduced into the reactor, or when there is an increase in the batch size as well as in the reactor volume, the reaction exotherm is controlled by a gradual addition of formaldehyde. Modern novolak production facilities are automated and programmed for reduced operational cost. A flow diagram of a general production line for the manufacture of novolak is shown. Recovery of the novolak is accomplished by the removal of water and devolatilization of crude novolak to molten, low-free phenol novolak resin which can be isolated as flake or pastille or dissolved in appropriate solvents. Novolak is stored either in a solid flake or pastille form or in solution. Most production is conducted under atmospheric conditions, but there are some recent, novel activities such as pressure in a hermetically-closed reactor reaching 0.1-10 MPa by using the heat of reaction without reflux to shorten reaction time, accelerating dehydration time by flash distillation, and providing economic benefit in the cost of novolak production.

  7. New Products.

    ERIC Educational Resources Information Center

    TechTrends, 1992

    1992-01-01

    Reviews new educational technology products, including a microcomputer-based tutoring system, laser barcode reader, video/data projectors, CD-ROM for notebook computers, a system to increase a printer's power, data cartridge storage shell, knowledge-based decision tool, video illustrator, interactive videodiscs, surge protectors, scanner system,…

  8. New Products.

    ERIC Educational Resources Information Center

    TechTrends, 1992

    1992-01-01

    Reviews new educational technology products, including a microcomputer-based tutoring system, laser barcode reader, video/data projectors, CD-ROM for notebook computers, a system to increase a printer's power, data cartridge storage shell, knowledge-based decision tool, video illustrator, interactive videodiscs, surge protectors, scanner system,…

  9. Environmental and biological monitoring of occupational formaldehyde exposure resulting from the use of products for hair straightening.

    PubMed

    Peteffi, Giovana Piva; Antunes, Marina Venzon; Carrer, Caroline; Valandro, Eduarda Trevizani; Santos, Sílvia; Glaeser, Jéssica; Mattos, Larissa; da Silva, Luciano Basso; Linden, Rafael

    2016-01-01

    The evaluation of formaldehyde (FD) exposure in beauty salons, due to the use of hair straightening products, and its relation with genotoxicity biomarkers was performed in this study. Regardless of official recommendations, the inappropriate use of homemade hair creams has became a popular practice in Brazil, and high formaldehyde content in the "progressive straightening" creams can contain mutagens that could increase the incidence of neoplasia in those people who use them. Damage to DNA was assessed by conducting a micronuclei test (MNT) on buccal cells and the comet assay on heparinized venous blood samples. A total of 50 volunteers were recruited at six different beauty salons (labeled A to F). At two salons that used products that did not contain FD (salons D and E), environmental FD concentrations were 0.04 and 0.02 ppm. In contrast, the products used at salons A, B, C, and F contained 5.7, 2.61, 5.9, and 5.79% of FD, and these salons had environmental FD concentrations of 0.07, 0.14, 0.16, and 0.14 ppm, respectively. Comparison of the beauty salon workers from each of the six beauty salons revealed significant differences in urinary formic acid (FA) concentration before exposure (p = 0.016), urinary FA after exposure (p = 0.004), variation in FA concentration before and after exposure (p = 0.018), environmental FD concentration (p < 0.001), cytogenetic damage detected by the comet assay according to both damage index (p < 0.001) and frequency of damage (p < 0.001), and for karyorrhexis only according to the MNT (p = 0.001).

  10. Tequila production.

    PubMed

    Cedeño, M

    1995-01-01

    Tequila is obtained from the distillation of fermented juice of agave plant, Agave tequilana, to which up to 49% (w/v) of an adjunct sugar, mainly from cane or corn, could be added. Agave plants require from 8 to 12 years to mature and during all this time cleaning, pest control, and slacken of land are required to produce an initial raw material with the appropriate chemical composition for tequila production. Production process comprises four steps: cooking to hydrolyze inulin into fructose, milling to extract the sugars, fermentation with a strain of Saccharomyces cerevisiae to convert the sugars into ethanol and organoleptic compounds, and, finally, a two-step distillation process. Maturation, if needed, is carried out in white oak barrels to obtain rested or aged tequila in 2 or 12 months, respectively.

  11. Product separator

    DOEpatents

    Welsh, Robert A.; Deurbrouck, Albert W.

    1976-01-20

    A secondary light sensitive photoelectric product separator for use with a primary product separator that concentrates a material so that it is visually distinguishable from adjacent materials. The concentrate separation is accomplished first by feeding the material onto a vibratory inclined surface with a liquid flow, such as a wet concentrating table. Vibrations generally perpendicular to the stream direction of flow cause the concentrate to separate from its mixture according to its color. When the concentrate and its surrounding stream reach the recovery end of the table, a detecting device notes the line of color demarcation and triggers a signal if it differs from a normal condition. If no difference is noted nothing moves on the second separator. However, if a difference is detected in the constant monitoring of the color line's location, a product splitter and recovery unit normally positioned near the color line at the recovery end, moves to a new position. In this manner the selected separated concentrate is recovered at a maximum rate regardless of variations in the flow stream or other conditions present.

  12. 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

  13. Metallized Products

    NASA Technical Reports Server (NTRS)

    1980-01-01

    Since the early 1960's, virtually all NASA spacecraft have used metallized films for a variety of purposes, principally thermal radiation insulation. King Seeley manufactures a broad line of industrial and consumer oriented metallized film, fabric, paper and foam in single layer sheets and multi-layer laminates. A few examples, commercialized by MPI Outdoor Safety Products, are the three ounce Thermos Emergency Blanket which reflects and retains up to 80 percent of the user's body heat helping prevent post accident shock or keeping a person warm for hours under emergency cold weather conditions.

  14. Software Products

    NASA Technical Reports Server (NTRS)

    1993-01-01

    MAST is a decision support system to help in the management of dairy herds. Data is collected on dairy herds around the country and processed at regional centers. One center is Cornell University, where Dr. Lawrence Jones and his team developed MAST. The system draws conclusions from the data and summarizes it graphically. CLIPS, which is embedded in MAST, gives the system the ability to make decisions without user interaction. With this technique, dairy managers can identify herd problems quickly, resulting in improved animal health and higher milk quality. CLIPS (C Language Integrated Production System) was developed by NASA's Johnson Space Center. It is a shell for developing expert systems designed to permit research, development and delivery on conventional computers.

  15. SaferProducts.gov

    MedlinePlus

    ... Register & Respond Search Recalls & Reports About Questions Welcome Consumers Report your unsafe product on SaferProducts.gov. Tell ... adequacy of the contents of the Publicly Available Consumer Product Safety Information Database on SaferProducts.gov, particularly ...

  16. Household Products Database

    MedlinePlus

    ... Care Landscape/Yard Arts & Crafts Pet Care Pesticides Auto Products Home Office Commercial / Institutional Product Names Types of Products Manufacturers Ingredients About the Database FAQ Product Recalls Help Glossary Contact Us More Resources What's under your ...

  17. Productivity, components of automated production systems viewed

    NASA Astrophysics Data System (ADS)

    Letsik, V. I.

    1986-03-01

    The developmet and expanded use of robotics was initiated to increase labor productivity, ensure stable high quality instruments and necessary safety equipment, and to reduce the cost of products. Robotics was introduced to cold stamping machining, loading and unloading, transport and warehousing, etc. Approximately 200 robots were introduced which replaced 50 people. Robotics and robotized technology applied to industrial plants for automation flexible production systems, increase productivity, quality improvement, and reduction of manpower is discussed.

  18. Biological production of products from waste gases

    DOEpatents

    Gaddy, James L.

    2002-01-22

    A method and apparatus are designed for converting waste gases from industrial processes such as oil refining, and carbon black, coke, ammonia, and methanol production, into useful products. The method includes introducing the waste gases into a bioreactor where they are fermented to various products, such as organic acids, alcohols, hydrogen, single cell protein, and salts of organic acids by anaerobic bacteria within the bioreactor. These valuable end products are then recovered, separated and purified.

  19. CD-ROM Catalog Production Products.

    ERIC Educational Resources Information Center

    Bills, Linda; Helgerson, Linda

    1989-01-01

    Compares database characteristics, access, display, editing, new records, hard copy products, hardware, and price of CD-ROM catalog production products from seven vendors: Gaylord Information Systems; General Research Corporation; The Library Corporation; OCLC; Solinet; Utlas; and the Western Library Network. (MES)

  20. CD-ROM Catalog Production Products.

    ERIC Educational Resources Information Center

    Bills, Linda; Helgerson, Linda

    1989-01-01

    Compares database characteristics, access, display, editing, new records, hard copy products, hardware, and price of CD-ROM catalog production products from seven vendors: Gaylord Information Systems; General Research Corporation; The Library Corporation; OCLC; Solinet; Utlas; and the Western Library Network. (MES)

  1. Southern pulpwood production, 1986

    Treesearch

    Dennis M. May

    1988-01-01

    In 1986, Southern pulpwood production increased 6 percent, to 60.6 million cords; roundwood production increased 9 percent, to 40.4 million cords; and wood residue production increased 2 percent, to 20.1 million cords. Since 1977, roundwood production has been increasing while wood residue production has leveled off. Hardwoods have been capturing a larger proportion...

  2. Root production method system

    Treesearch

    Wayne Lovelace

    2002-01-01

    The RPM system (Root Production Method) is a multistep production system of container tree production that places primary emphasis on the root system because the root system ultimately determines the tree's survival and performance in its outplanted environment. This particular container production system has been developed to facilitate volume production, in a...

  3. By-Product Feeds

    USDA-ARS?s Scientific Manuscript database

    By-product feeds are generated from the production of food, fiber, and bio-energy products for human consumption. They include plant feedstuffs such as hulls, stalks, peels, and oil seed meals, and animal by-products such as blood meal, fats, bone meal, or processed organ meats. Some feed by-product...

  4. Method derives production costs of refined products

    SciTech Connect

    Bernasconi, F.

    1987-02-09

    Production costs of refined petroleum products can be determined from a simple and accurate method that enables the user to calculate the break even value (BEV) to the refiner of all finished products, from different grades of gasoline and middle distillate, to specialties such as bitumens and lube basestocks. The method, developed by Chem Systems, can also assess the effect on BEV of refinery configuration, mode of operation, and type of crude oil processes. The BEV's are determined as a function of crude and residual fuel oil prices and are not influenced by the market price of the white products. The ability to determine the production cost of a given product is a most valuable aid to the refiner, not just an academic exercise. Two important applications are ''make or buy'' decisions to meet needs for incremental amounts of product above the refinery baseload and the possibility of focusing refining operation on products that show the highest contribution to overall margins. For these reasons, the determination of the production costs of petroleum products is a subject which is attracting increasing interest. However, while it is relatively easy to calculate the overall cost of refining crude, it is not feasible to break this cost down by the various products produced. In fact, attempts to do so would be completely arbitrary.

  5. Product Structure, the Heart of Product Definition

    NASA Technical Reports Server (NTRS)

    DeHoog, C., Jr.

    1999-01-01

    This paper describes the LMMSS Product Definition System (PDS) philosophy and approach were the use of each item parts document or software can be traced to a specific end item (EI) serial/tail number of the product. It explains why a part-oriented approach to data organization and configuration management is required. The definition of part-oriented is that all appropriate product definition data products will be collected. Referenced and managed by their linkage/relationship to parts/items, The paper will touch upon how LMMSS store/controls product definition information under each project's top product designator in a two tiered approach. One tier for each product end item and another tier which contain/controls listings of drawings, documents. Specifications and standards that are required for hardware item definition.

  6. Product Structure, the Heart of Product Definition

    NASA Technical Reports Server (NTRS)

    DeHoog, C., Jr.

    1999-01-01

    This paper describes the LMMSS Product Definition System (PDS) philosophy and approach were the use of each item parts document or software can be traced to a specific end item (EI) serial/tail number of the product. It explains why a part-oriented approach to data organization and configuration management is required. The definition of part-oriented is that all appropriate product definition data products will be collected. Referenced and managed by their linkage/relationship to parts/items, The paper will touch upon how LMMSS store/controls product definition information under each project's top product designator in a two tiered approach. One tier for each product end item and another tier which contain/controls listings of drawings, documents. Specifications and standards that are required for hardware item definition.

  7. Restrictions on Rodenticide Products

    EPA Pesticide Factsheets

    Consumer size products contain one pound of poison bait or less and must include a bait station. Products formulated for pest control professionals also meet certain requirements. Read the product label to ensure safe and effective use.

  8. Choosing Safe Baby Products

    MedlinePlus

    ... Looking for Health Lessons? Visit KidsHealth in the Classroom What Other Parents Are Reading Your Child's Development ( ... Safe Baby Products: Bathtubs Choosing Safe Baby Products: Changing Tables Choosing Safe Baby Products: Cribs Choosing Safe ...

  9. Science and Product.

    ERIC Educational Resources Information Center

    Gomory, Ralph E.; Schmitt, Roland W.

    1988-01-01

    Defines incremental product development and discusses how this style of innovation effects technology industries. Cites examples of Japanese competition which emphasizes quality and speed in product development. Makes recommendations for the improvement of product development in the United States. (CW)

  10. Household Products Database: Pesticides

    MedlinePlus

    ... Names Types of Products Manufacturers Ingredients About the Database FAQ Product Recalls Help Glossary Contact Us More ... holders. Information is extracted from Consumer Product Information Database ©2001-2016 by DeLima Associates. All rights reserved. ...

  11. Nail Care Products

    MedlinePlus

    ... Drug, or Both? (Or Is It Soap?)". By law, nail products sold in the United States must ... only" (see Cosmetic Labeling: An Overview ). Under the law, cosmetic products and ingredients, including nail products, do ...

  12. Southern pulpwood production, 1997

    Treesearch

    Tony G. Johnson; Carolyn D. Steppleton

    1999-01-01

    In 1997, the South's production of pulpwood increased 11 percent to 75.9 million cords. Roundwood production increased to 54.2 million cords and accounted for 71 percent of the total pulpwood production. The use of wood residue increased to 21.7 million cords. Alabama leads the South in total production, number of mills, and pulping capacity. Currently, 103 mills...

  13. Southern pulpwood production, 1994

    Treesearch

    Tony G. Johnson; Michael Howell

    1996-01-01

    The South's production of pulpwood increased 2 percent to 68.5 million cords. Roundwood production increased to 47.8 million cords and accounted for 70 percent of the total pulpwood production. The use of residue increased 3 percent to 20.7 million cords. Alabama leads the South in total production, number of mills, and pulping capacity. Currently 104 mills'...

  14. Southern pulpwood production, 1995

    Treesearch

    Tony G. Johnson; Carolyn D. Steppleton

    1996-01-01

    In 1995, the South's production of pulpwood increased 6 percent to 72.7 million cords. Roundwood production increased to 52.0 million cords and accounted for 72 percent of the total pulpwood production. The use of wood residue remained stable at 20.7 million cords. Alabama leads the South in total production, number of mills, and pulping capacity. Currently, 105...

  15. Southern pulpwood production, 1999

    Treesearch

    Tony G. Johnson; Carolyn D. Steppleton

    2001-01-01

    In 1999, the South's production of pulpwood declined 5 percent to 71.1 million cords. Roundwood production dropped to 49.2 million cords and accounted for 69 percent of the total pulpwood production. The use of wood residue remained stable at 21.9 million cords. Alabama continues to lead the South in total production, number of mills, and pulping capacity....

  16. Southern pulpwood production, 1996

    Treesearch

    Tony G. Johnson; Carolyn D. Steppleton

    1997-01-01

    In 1996, the South's production of pulpwood decreased 6 percent to 68.5 million cords. Roundwood production decreased to 49.6 million cords and accounted for 72 percent of the total pulpwood production. The use of wood residue declined to 19.0 million cords. Alabama leads the South in total production, number of mills, and pulping capacity. Currently, 105 mills...

  17. Southern pulpwood production, 1998

    Treesearch

    Tony G. Johnson; Carolyn D. Steppleton

    2000-01-01

    In 1998, the South's production of pulpwood declined 2 percent to 74.7 million cords. Roundwood production dropped to 52.7 million cords and accounted for 71 percent of the total pulpwood production. The use of wood residue increased to 21.9 million cords. Alabama leads the South in total production, number of mills, and pulping capacity. Currently, 103 mills are...

  18. Consumer Product Category Database

    EPA Pesticide Factsheets

    The Chemical and Product Categories database (CPCat) catalogs the use of over 40,000 chemicals and their presence in different consumer products. The chemical use information is compiled from multiple sources while product information is gathered from publicly available Material Safety Data Sheets (MSDS). EPA researchers are evaluating the possibility of expanding the database with additional product and use information.

  19. Information and Productivity.

    ERIC Educational Resources Information Center

    Bearman, Toni Carbo; And Others

    1985-01-01

    Addresses the role of information technology and effective management of information resources in reversing declining rate of growth of productivity in United States. Discussion covers U.S. productivity, reasons for decline in its growth, productivity measurement, improving productivity, and related activities of National Commission on Libraries…

  20. Eggs and Egg Products

    USDA-ARS?s Scientific Manuscript database

    The total U. S. egg production in 2009 was 78.5 billion table eggs, with 24 billion broken for the production of egg products. Shell eggs have many uses in homes, restaurants, and institutions, either alone or as ingredients in other foods. Egg products are also popular with consumers and are used i...

  1. Successful product realization strategies

    NASA Technical Reports Server (NTRS)

    Peeples, John; Boulton, William R.

    1995-01-01

    Product realization is the process of defining, designing, developing, and delivering products to the market. While the main thrust of this JTEC panel was to conduct a complete investigation of the state of Japanese low-cost electronic packaging technologies, it is very difficult to totally separate the development of technology and products from the product realization process. Japan's electronics firms adhere to a product realization strategy based on a strong customer focus, a consistent commitment to excellence in design, and a cost-effective approach to technology commercialization. The Japanese product-pull strategy has been a successful driver and influencing factor in every aspect of the product development cycle.

  2. Production Function Geometry with "Knightian" Total Product

    ERIC Educational Resources Information Center

    Truett, Dale B.; Truett, Lila J.

    2007-01-01

    Authors of principles and price theory textbooks generally illustrate short-run production using a total product curve that displays first increasing and then diminishing marginal returns to employment of the variable input(s). Although it seems reasonable that a temporary range of increasing returns to variable inputs will likely occur as…

  3. Production Function Geometry with "Knightian" Total Product

    ERIC Educational Resources Information Center

    Truett, Dale B.; Truett, Lila J.

    2007-01-01

    Authors of principles and price theory textbooks generally illustrate short-run production using a total product curve that displays first increasing and then diminishing marginal returns to employment of the variable input(s). Although it seems reasonable that a temporary range of increasing returns to variable inputs will likely occur as…

  4. Exposure to 915 MHz radiation induces micronuclei in Vicia faba root tips.

    PubMed

    Gustavino, Bianca; Carboni, Giovanni; Petrillo, Roberto; Paoluzzi, Giovanni; Santovetti, Emanuele; Rizzoni, Marco

    2016-03-01

    The increasing use of mobile phones and wireless networks raised a great debate about the real carcinogenic potential of radiofrequency-electromagnetic field (RF-EMF) exposure associated with these devices. Conflicting results are reported by the great majority of in vivo and in vitro studies on the capability of RF-EMF exposure to induce DNA damage and mutations in mammalian systems. Aimed at understanding whether less ambiguous responses to RF-EMF exposure might be evidenced in plant systems with respect to mammalian ones, in the present work the mutagenic effect of RF-EMF has been studied through the micronucleus (MN) test in secondary roots of Vicia faba seedlings exposed to mobile phone transmission in controlled conditions, inside a transverse electro magnetic (TEM) cell. Exposure of roots was carried out for 72h using a continuous wave (CW) of 915 MHz radiation at three values of equivalent plane wave power densities (23, 35 and 46W/m(2)). The specific absorption rate (SAR) was measured with a calorimetric method and the corresponding values were found to fall in the range of 0.4-1.5W/kg. Results of three independent experiments show the induction of a significant increase of MN frequency after exposure, ranging from a 2.3-fold increase above the sham value, at the lowest SAR level, up to a 7-fold increase at the highest SAR. These findings are in agreement with the limited number of data on cytogenetic effects detected in other plant systems exposed to mobile phone RF-EMF frequencies and clearly show the capability of radiofrequency exposure to induce DNA damage in this eukaryotic cell system.

  5. Anticlastogenic effects of galangin against mitomycin C-induced micronuclei in reticulocytes of mice.

    PubMed

    Heo, M Y; Jae, L H; Jung, S S; Au, W W

    1996-05-17

    We investigated the suppressive effect of galangin on the induction of micronucleated reticulocytes (MNRETs) by mitomycin C (MMC) in mouse peripheral blood. When galangin was given to mice 24 h before the intraperitoneal injection of MMC (1 mg/kg), a more marked decrease in the frequency of MNRETs was observed than in mice with simultaneous and post-treatment of galangin. On the other hand, when galangin was given to mice for 7 consecutive days before MMC injection, galangin showed potent anticlastogenic effects, even at the lowest dose level of 0.1 mg/kg. Results from our in vivo studies indicate that galangin is capable of suppressing the clastogenic activity of the direct acting MMC. Together with our earlier observations, it appears that galangin is capable of protecting cells from the toxic effects of a variety of hazardous chemicals. Therefore, galangin may be an useful chemopreventive compound.

  6. Increased frequency of micronuclei in peripheral blood lymphocytes of subjects infected with Helicobacter pylori.

    PubMed

    Suárez, Susanna; Sueiro, Rosa Ana; Araujo, Manuel; Pardo, Fernanda; Menéndez, M Dolores; Pardiñas, M Carmen; Alvarez, Angel

    2007-01-10

    Epidemiological studies have demonstrated a close association between infection with Helicobacter pylori and the development of gastric carcinoma and mucosa-associated lymphoid tissue lymphomas in humans. The cytokinesis-block micronucleus assay was performed on peripheral blood lymphocytes of H. pylori-infected patients in order to investigate the possible induction of genotoxic damage. The study group consisted of 70 infected subjects including 33 women and 37 men, and 66 healthy controls (37 females and 29 males). Our results indicate that in the infected group the overall frequency of binucleated micronucleated cells (BNMN) per 1000 cells was higher (17.65+/-1.55) than in the controls (7.39+/-0.66), this difference being statistically significant. No differences were found between the infected and control groups regarding the cytokinesis-block proliferation index (CBPI). When the effect of different counfounding factors was evaluated, mutivariate statistical analysis revealed that age and alcohol consumption modulated the frequency of BNMN in infected people, and the interaction between alcohol use-smoking-infection also affected the BNMN frequency in H. pylori patients. Our results indicate that infection by H. pylori is associated with an increased level of cytogenetic damage in the cells of the host.

  7. Micronuclei in neonates and children: effects of environmental, genetic, demographic and disease variables

    PubMed Central

    Holland, Nina; Fucic, Alexandra; Merlo, Domenico Franco; Sram, Radim; Kirsch-Volders, Micheline

    2011-01-01

    Children may be more susceptible to the effects of the environmental exposure and medical treatments than adults; however, limited information is available about the differences in genotoxic effects in children by age, sex and health status. Micronucleus (MN) assay is a well established method of monitoring genotoxicity, and this approach is thoroughly validated for adult lymphocytes by the Human Micronucleus Biomonitoring project (HUMN.org). Similar international undertaking is in progress for exfoliated buccal cells. Most of the MN studies in children are focused on analyses of lymphocytes but in the recent years, more investigators are interested in using exfoliated cells from the oral cavity and other cell types that can be collected non-invasively, which is particularly important in paediatric cohorts. The baseline MN frequency is relatively low in newborns and its assessment requires large cohorts and cell sample counts. Available results are mostly consistent in conclusion that environmental pollutants and radiation exposures lead to the increase in the MN frequency in children. Effects of medical treatments are less clear, and more studies are needed to optimise the doses and minimise genotoxicity without compromising therapy outcomes. Despite the recent progress in MN assay in children, more studies are warranted to establish the relationship between MN in lymphocytes and exfoliated cells, to clarify sex, age and genotype differences in baseline MN levels and the changes in response to genotoxicants. One of the most important types of MN studies in children are prospective cohorts that will help to clarify the predictive value of MN and other cytome end points for cancer and other chronic diseases of childhood and adulthood. Emerging ‘omic’ and other novel molecular technologies may shed light on the molecular mechanisms and biological pathways associated with the MN levels in children. PMID:21164182

  8. In vitro micronuclei tests to evaluate the genotoxicity of surface water under the influence of tanneries.

    PubMed

    Lemos, A O; Oliveira, N C D; Lemos, C T

    2011-06-01

    Leather manufacturing has a high potential for environmental pollution due to hides and chemicals that are not completely absorbed during the tanning process. This study aims to investigate the mutagenic potential of surface water samples from Cadeia and Feitoria rivers (RS, Brazil) in areas influenced by tanneries and leather footwear industry. Micronucleus assays using V79 cells and human lymphocytes were used. Cells were exposed to surface water collected bimonthly from three sites for a year, totaling six samples. Significant MN induction in human lymphocytes was shown by 83% of samples from sites FEI001 and CAD001 located downstream from the industrial area, followed by FEI004 (33%), upstream. Only a single sample from site FEI004 showed a positive response for MN in V79 cells. Thirteen discordant and five concordant responses were found between the two in vitro tests. Mutagenic agents were found at the sites where chemical quality was worst, corroborating studies on chronic toxicity, oxidative stress and mutagenicity performed in this area. The assay using human lymphocytes was more sensitive than V79 cells to detect the contaminants from this area, showing that it is an excellent biomarker of environmental genotoxicity. Copyright © 2011 Elsevier Ltd. All rights reserved.

  9. Nuclear differentiation in Paramecium tetraurelia. Transplantation of vegetative micronuclei into early exconjugants.

    PubMed

    Mikami, K; Ng, S F

    1983-03-01

    The micronucleus of Paramecium tetraurelia normally gives rise to the macronucleus by going through the series of nuclear events of meiosis, mitosis and fusion during sexual reproduction. By transplanting the micronucleus from vegetative cells into early exconjugants, we have persuaded the micronucleus to take a short cut to differentiate directly into a macronucleus. This demonstrates that the course of development of the micronucleus is flexible and can be altered by stage-specific cytoplasmic factors.

  10. Determination of diesel genotoxicity in firebreathers by micronuclei and nuclear abnormalities in buccal mucosa.

    PubMed

    Torres-Bugarín, O; De Anda-Casillas, A; Ramírez-Muñoz, M P; Sánchez-Corona, J; Cantú, J M; Zúñiga, G

    1998-03-30

    Diesel or its derivatives could have aneuploidogenic and/or clastogenic activity. Hence, the genotoxicity of diesel gases has been studied, considering exposure to them as potentially carcinogenic. The results obtained by different authors suggest the need to know the effects of direct and chronic exposure to diesel in humans, as in the case of the street workers called 'firebreathers' who fill their buccal cavity with diesel and then spread it to a burning torch many times during the day in order to give a 'dragon show' for 5 h a day and 6 days a week. The buccal samples of eight firebreathers were collected, processed and scored according to the criterion established by Tolbert et al., 1992 and then compared with positive and negative control groups. The results revealed that diesel was not micronucleogenic although it induces some nuclear abnormalities.

  11. In situ monitoring of animal micronuclei before the operation of Daya Bay Nuclear Power Station

    SciTech Connect

    Y.N. Cai; H.Y. He; L.M. Qian; G.C. Sun; J.Y. Zhao

    1994-12-31

    Daya Bay Nuclear Power Station, a newly-built nuclear power station in southern mainland China, started its operation in 1993. We examined micro-nucleated cells of Invertibrate (Bivalves) and Vertibrate (Fish and Amphibia) in different spots within the 50km surroundings of the Power Station during 1986-1993. This paper reports the results of the investigation carried out in Dong Shan, a place 4.7km to the Power Station:Bivalves; Pteria martensil 5.1(1986),4.8(1988),4.8(1991),5,0(1993),Mytilus smardinus 4.7(1987),4.6(1988); Chamys nobilis 4.9(1987);4.9(1991),4.5(1992),4.5(1993). Fish; Therapon jarbua 0.48(1991),0.67(1992),0.47(1993). Amphibia; Bufo melanostictus 0.29 (1987), 0.34(1988),0.39(1992),0.39(1993). These results showed that the environmental situation, estimated by using the frequencies of micronucleated cells, was stable-there was no obvious chromosome damage in the animals studied. It was found that the incidence of micronucleated cells of Bivalves was higher than that of Fish and Amphibia, suggesting the epithelial cells to be more sensitive than peripheral erythrocytes to environmental genotoxic effects. The results of our studies for other spots will be reported afterward. These data can be used as the original background information to monitor the environment when the Nuclear Power Station is in operation.

  12. Micronuclei and nuclear abnormalities in buccal mucosa cells in patients with anorexia and bulimia nervosa.

    PubMed

    Torres-Bugarín, Olivia; Pacheco-Gutiérrez, Angélica Guadalupe; Vázquez-Valls, Eduardo; Ramos-Ibarra, María Luisa; Torres-Mendoza, Blanca Miriam

    2014-11-01

    The aim of this study is to assess the frequency of micronucleated cell (MNC) and nuclear abnormalities (NA) in the buccal mucosa cells of females with anorexia nervosa (AN) or bulimia nervosa (BN), compared with healthy women. Individuals with AN and BN have inadequate feeding and compensatory behaviour to avoid weight gain. These behaviours can cause extreme body stress, thereby inducing DNA damage. In a cross-sectional study, we assessed the frequency of MNC and NA in the buccal mucosa cells of female participants with AN or BN. All of these patients had been admitted to a private clinic for the treatment of eating disorders after diagnosis with AN (n = 10) or BN (n = 7) according to the DSM-IV. Age-matched healthy female participants (n = 17) composed the control group. Oral mucosa samples were collected, fixed, stained by aceto-orcein/fast green and microscopically examined. Normal cells, MNC and NAs were counted within a 2000 cell sample. The results were analyzed with the Kruskal-Wallis and Mann-Whitney tests. Differences were observed in the frequency of MNC in healthy females (1.2±0.9) versus that of patients with AN (3.4±1.5) (P < 0.0001) and BN (4.1±2.2) (P < 0.001). No differences were found among these groups in terms of NA. AN and BN are related to the loss of genetic material through chromosomal fractures and/or damage to the mitotic spindle (i.e. possibly a result of a deficiency in DNA precursors). Self-imposed compensatory behaviours in AN and BN, such as severe food restriction, potential malnutrition, vomiting, use of diuretics and laxatives and acute exhaustive exercise, are possible inducers of MNC and genotoxic damage. Of these compensatory behaviours, only vomiting has not been linked to genotoxic damage. This is the first report in women with BN, which should be studied in the future.

  13. Arsenic-induced micronuclei formation in mammalian cells and its counteraction by tea.

    PubMed

    Sinha, Dona; Roy, Madhumita; Siddiqi, Maqsood; Bhattacharya, Rathin K

    2005-01-01

    The Gangetic plain of West Bengal, India, has been engulfed by a disastrous environmental calamity of arsenic contamination of the ground water. Chronic arsenic toxicity caused by drinking arsenic-contaminated water has been one of the worst health hazards gradually affecting nine districts of West Bengal since the early 1980s. Over and above hyperpigmentation and keratosis,weakness, burning sensation of the eyes, swelling of the legs, liver fibrosis, chronic lung disease, gangrene of the toes, neuropathy, and skin cancer are other manifestations. Induction of cancer is frequently associated with DNA damage, changes in ploidy of cells, and non-random chromosome aberrations. Counteraction of these genotoxic and cytogenetic abnormalities with natural dietary polyphenols could be a useful strategy to combat arsenic-induced DNA damage and thereby cancer. A review of the literature showed that it is the antioxidant property of tea polyphenols that affords protection against various types of cancer. The present study was conducted to investigate whether the extracts of green tea and black tea (Darjeeling and Assam) as well as their polyphenols could ameliorate this arsenic-induced genotoxicity. The normal mammalian cell culture derived from male Chinese hamster lung fibroblast cells (V79) was used as the test system to assess the genotoxicity by micronucleus assay. The results showed that both green tea and black tea extracts have equal potential in modulating the arsenic-induced genotoxicity. This effect was perhaps induced by the constituent polyphenols present in green and black tea. In addition, the repair activity of the damaged cells was enhanced when treated with these tea extracts and their polyphenols. Thus, tea and its polyphenols may have a promising role in counteracting the devastating effects of arsenic.

  14. Induction of micronuclei and aneuploidy by the quinone-forming agents benzene and o-phenylphenol.

    PubMed

    Eastmond, D A

    1993-04-01

    A number of carcinogens appear to exert their tumorigenic effects through the formation of quinone metabolites. These quinone-forming carcinogens are generally inactive or weakly active in standard gene mutation assays. Accumulating evidence indicates that this class of compounds may exert their genotoxic and carcinogenic effects through the induction of large-scale gene alterations. This article presents an overview of work that has been performed using recently developed molecular cytogenic techniques to investigate the aneuploidy-inducing and clastogenic properties of the major quinone-forming metabolites of benzene, a widely used industrial chemical, and o-phenylphenol, a fungicide and disinfectant. These metabolites of benzene (hydroquinone, catechol, and benzenetriol) and o-phenylphenol (phenylhydroquinone) have each been shown to be capable of interfering with chromosome segregation and inducing chromosomal breakage. These results indicate that both numerical and structural chromosomal aberrations induced by the quinone metabolites of benzene and o-phenylphenol may play a role in the carcinogenic effects of these two agents.

  15. Malnutrition and infection influence the peripheral blood reticulocyte micronuclei frequency in children.

    PubMed

    Cervantes-Ríos, Elsa; Ortiz-Muñiz, Rocío; Martínez-Hernández, Ana Lidia; Cabrera-Rojo, Lilián; Graniel-Guerrero, Jaime; Rodríguez-Cruz, Leonor

    2012-03-01

    Malnutrition is a serious public health problem that affects approximately one third of all children. Developing countries have the highest incidence of malnourished children, and approximately 60% of deaths that occur in children under five are directly related to malnutrition and associated diseases. The relationship between malnutrition and genetic damage has been widely studied in humans and animal models. The micronucleus (MN) assay is useful in detecting chromosome damage induced by several factors. The aim of this study was to evaluate the effects of infection and malnutrition on the frequency of MN in erythrocytes from the peripheral blood of well-nourished, uninfected (WN) and well-nourished, infected (WNI) children, and moderately malnourished (UNM) and severely malnourished (UNS) children, both with infection, using a flow cytometric analysis technique. The percentage of reticulocytes (RETs) was significantly higher (1.5-fold) in WNI children than well-nourished controls. In addition, the UNS group had a 2.2-fold increase in the percentage of RETs compared to the WNI group. The frequency of micronucleated reticulocytes (MN-RETs) was 2.5 times greater, in WNI group compared to the WN group. These frequencies were significantly higher (1.7- and 2.1-fold) in UNM and UNS, respectively, compared to the WNI group. The results suggest that infection and malnutrition induce DNA damage in children. Copyright © 2011 Elsevier B.V. All rights reserved.

  16. Shiitake (Lentinula edodes (Berkeley) Pegler) extracts as a modulator of micronuclei induced in HEp-2 cells.

    PubMed

    Miyaji, C K; Poersch, A; Ribeiro, L R; Eira, A F; Cólus, I M S

    2006-12-01

    Shiitake (Lentinula edodes (Berkeley) Pegler) is one of the most consumed mushrooms, for both therapeutic purposes and as food, therefore, the study of its biological properties is of great interest for producers and consumers. Aqueous extracts of the shiitake mushroom (L. edodes (Berkeley) Pegler) were evaluated by the micronucleus test (MN) in HEp-2 cells in vitro, to analyze their possible mutagenic and antimutagenic activities. None of the three extract concentrations tested (0.5, 1.0 and 1.5mg/mL) presented mutagenicity at any of the preparation temperatures (4 degrees C, 22+/-2 degrees C and 60 degrees C). In the antimutagenicity evaluation, all extract concentrations at all preparation temperatures presented a strong protective activity for the HEp-2 cells in response to the alkylating agent methyl methanesulfonate (MMS) in the different treatment protocols: pre-treatment, simultaneous treatment and post-treatment. The extracts prepared at 22+/-2 degrees C presented the lowest frequencies of MN in the evaluations of mutagenicity and antimutagenicity, indicating these as the best option for potential therapeutic use.

  17. Micronuclei and nuclear anomalies in urinary exfoliated cells of subjects in radionuclide-contaminated regions.

    PubMed

    Jen, Min Huan; Hwang, Jeng-Jeng; Yang, Jao-Yeh; Nabyvanets, Yuriy B; Hsieh, Wanhwa A; Tsai, Mon-Hsung; Guo, Shin-Diau; Chang, Wushou P

    2002-09-26

    (137)Cs contamination in living or agricultural environments may contribute to significant human internal exposure and cause adverse health effects. Contamination by (137)Cs and other radionuclides was detected in a river valley in northern Taiwan, in the 1990s. Given that the radioactivity appeared to be widely distributed in soil, rice and several other food plants in the areas surrounding several communities in the late 1990s [Y.B. Nabyvanents, T.F. Gesell, M.H. Jen, W.P. Chang, Distribution of (137)Cs in soil along Ta-han River Valley in Tau-Yuan County in Taiwan, J. Environ. Radioact. 54 (2001) 391], its possible impact on local occupants was further studied. Ten subjects in three families residing continuously in the highly contaminated valley and 10 non-exposed subjects matched for age, sex, and cigarette smoking habits from neighboring communities were evaluated for micronucleus frequencies and for degenerative nuclear changes in urinary exfoliated epithelial cells (EE cells). Micronucleus frequencies ( per thousand ) were significantly higher in the exposed subjects (4.79+/-1.21 per thousand ) than in the reference subjects (2.73+/-0.59 per thousand; Wilcoxon 2-sample test, P value 0.0004). There were also higher frequencies of EE cells with karyolysis and condensed chromatin in the exposed subjects than in reference subjects. These results indicate that genotoxic and/or mutagenic effects on urinary epithelial cells occur in human subjects who have resided for a long time in a radioactively contaminated environment.

  18. Nucleus-specific and temporally restricted localization of proteins in Tetrahymena macronuclei and micronuclei

    PubMed Central

    1989-01-01

    Labeled nuclear proteins were microinjected into the cytoplasm of Tetrahymena thermophila. Macronuclear H1, calf thymus H1, and the SV40 large T antigen nuclear localization signal linked to BSA accumulated specifically in macronuclei, even if cells were in micronuclear S phase or were nonreplicating. The way in which histone H4 localized to either the macronucleus or the micronucleus suggested that it accumulates in whichever nucleus is replicating. The inability of the micronucleus to accumulate Tetrahymena H1 or heterologous nuclear proteins, even at a period in the cell cycle when it is accumulating H4, suggests that it has a specialized transport system. These studies demonstrate that although the mechanism for localizing proteins to nuclei is highly conserved among eukaryotes, it can differ between two porecontaining nuclei lying in the same cytoplasm. PMID:2553740

  19. Association between human papillomavirus (HPV) DNA and micronuclei in normal cervical cytology

    PubMed Central

    Cassel, Ana Paula Rebelo; Barcellos, Regina Bones; da Silva, Cláudia Maria Dornelles; de Matos Almeida, Sabrina Esteves; Rossetti, Maria Lucia Rosa

    2014-01-01

    The aim of the present study was to investigate the association between HPV-DNA and micronucleus (MN) frequency in women with normal cervical cytology. A total of 158 normal cervical smears were analyzed cytologically. The HPV genome was amplified using the GP5+/bioGP6+ consensus primers. HPV-DNA of high-risk types 16, 18, 31, 33, 39, 45 and 59 were also investigated. Of the 158 samples, 20 (12.7%) and 47 (29.7%) were positive for HPV-DNA and MN, respectively. Evidence for MN was found in 11 out of 20 (55%) HPV-DNA positive samples and in 36 out of 138 (26.1%) HPV-DNA negative ones. MN presence was significantly higher in HPV-DNA positive samples (p = 0.016). On the other hand, the absence of MN observed in a considerable number of HPV-DNA negative samples (102) may be of great value in predicting the absence of HPV. The mean age of HPV-DNA positive women (34.2 ± 12.6) was significantly lower than the mean age of HPV-DNA negative women (43.9 ± 13.7) (p = 0.003). Infection by one or multiple HPV types was found in 11 out of 20 (55.0%) and 9 out of 20 (45.0%) samples, respectively. The evaluation of MN using cervical smears collected for cytology tests could, thus, be used as additional information to monitor a population’s exposure to HPV. PMID:25071400

  20. Association between human papillomavirus (HPV) DNA and micronuclei in normal cervical cytology.

    PubMed

    Cassel, Ana Paula Rebelo; Barcellos, Regina Bones; da Silva, Cláudia Maria Dornelles; de Matos Almeida, Sabrina Esteves; Rossetti, Maria Lucia Rosa

    2014-06-01

    The aim of the present study was to investigate the association between HPV-DNA and micronucleus (MN) frequency in women with normal cervical cytology. A total of 158 normal cervical smears were analyzed cytologically. The HPV genome was amplified using the GP5+/bioGP6+ consensus primers. HPV-DNA of high-risk types 16, 18, 31, 33, 39, 45 and 59 were also investigated. Of the 158 samples, 20 (12.7%) and 47 (29.7%) were positive for HPV-DNA and MN, respectively. Evidence for MN was found in 11 out of 20 (55%) HPV-DNA positive samples and in 36 out of 138 (26.1%) HPV-DNA negative ones. MN presence was significantly higher in HPV-DNA positive samples (p = 0.016). On the other hand, the absence of MN observed in a considerable number of HPV-DNA negative samples (102) may be of great value in predicting the absence of HPV. The mean age of HPV-DNA positive women (34.2 ± 12.6) was significantly lower than the mean age of HPV-DNA negative women (43.9 ± 13.7) (p = 0.003). Infection by one or multiple HPV types was found in 11 out of 20 (55.0%) and 9 out of 20 (45.0%) samples, respectively. The evaluation of MN using cervical smears collected for cytology tests could, thus, be used as additional information to monitor a population's exposure to HPV.

  1. DIETARY FOLATE DEFICIENCY ENHANCES INDUCTION OF MICRONUCLEI BY ARSENIC IN MICE

    EPA Science Inventory

    Folate deficiency increases background levels of DNA damage and can enhance the genotoxicity of chemical agents. Arsenic, a known human carcinogen present in drinking water supplies around the world, induces chromosomal and DNA damage. The effect of dietary folate deficiency on...

  2. DIETARY FOLATE DEFICIENCY ENHANCES INDUCTION OF MICRONUCLEI BY ARSENIC IN MICE

    EPA Science Inventory

    Folate deficiency increases background levels of DNA damage and can enhance the genotoxicity of chemical agents. Arsenic, a known human carcinogen present in drinking water supplies around the world, induces chromosomal and DNA damage. The effect of dietary folate deficiency on...

  3. Does radio frequency radiation induce micronuclei frequency in exfoliated bladder cells of diabetic rats?

    PubMed

    Gurbuz, N; Sirav, B; Kuzay, D; Ozer, C; Seyhan, N

    2015-07-01

    For many years there has been a discussion among both experts and the general public regarding the effects of radio frequency (RF) radiation on the human organism. The purpose of the present study was to evaluate the relationship of micronucleui (MN) frequency and RF radiation in exfoliated bladder cells of non-diabetic and diabetic rats. Three groups were used in the experiment: Group I (n=6): diabetic group without RF exposure; Group II (n=6): diabetic group exposed 2100 MHz RF radiation and Group III (n=6): control animals (non-diabetic group, no RF exposure). RF exposure in the experiment resulted in a whole body average SAR of 0.24 W/kg with an ERMS field of 17.5 V/m in non-thermal levels. Results showed that there was no statistically important differences between non-RF exposed diabetes group and control group; Group I and Group III (p>0.05). There was no statistically important differences between diabetes group and diabetes+RF exposed group (Group I and Group II) (p>0.05). RF exposure did not result in increased MN frequencies in exfoliated bladder cells of diabetic rats with respect to control animals (Group II and Group III), either and this result found no statistically important (p>0.05). This study suggested no possible genotoxic effects of RF radiation among human beings especially with chronic disorders, such as diabetes.

  4. Our Finished Product--Industry's Raw Product

    ERIC Educational Resources Information Center

    Johnson, L. Myron

    1978-01-01

    Comparing students in agribusiness sales, supply, and service courses to raw products in need of development, the author discusses the backgrounds of these students and their developing maturity through supervised occupational experience. (BM)

  5. Product assurance management and software product assurance

    NASA Technical Reports Server (NTRS)

    Schneider, C.; Borycki, G.; Panaroni, P.; Surbone, M.; Borcz, R.; Beddow, A. J.

    1991-01-01

    The evolution of software assurance is discussed. The definition and implementation of standards are considered. It is recommended that requirements be clarified at the start of a project. The need for quality assurance in hardware is identified as the coming trend in the production of high cost single units which call for eradication of all errors during the early stages of development. The need to apply quality assurance throughout the whole mission is stressed. The dangers of overpricing product assurance services is stressed.

  6. Transformer Industry Productivity Slows.

    ERIC Educational Resources Information Center

    Otto, Phyllis Flohr

    1981-01-01

    Annual productivity increases averaged 2.4 percent during 1963-79, slowing since 1972 to 1.5 percent; computer-assisted design and product standardization aided growth in output per employee-hour. (Author)

  7. Increasing productivity: Another approach

    SciTech Connect

    Norton, F.J.

    1996-06-10

    An engineering information (EI) and information technology (IT) organization that must improve its productivity should work to further its business goals. This paper explores a comprehensive model for increasing EI/IT productivity by supporting organizational objectives.

  8. Other Fluoride Products

    MedlinePlus

    ... What's this? Submit What's this? Submit Button Other Fluoride Products Recommend on Facebook Tweet Share Compartir On ... August 17, 2001;50(RR-14):1–42. Fluoride Products Fluoride Toothpaste Form Concentrations of fluoride in ...

  9. Transformer Industry Productivity Slows.

    ERIC Educational Resources Information Center

    Otto, Phyllis Flohr

    1981-01-01

    Annual productivity increases averaged 2.4 percent during 1963-79, slowing since 1972 to 1.5 percent; computer-assisted design and product standardization aided growth in output per employee-hour. (Author)

  10. Southern pulpwood production, 1981

    Treesearch

    Cecil C. Hutchins

    1982-01-01

    Southern pulpwood production has remained almost constant for the past 3 years. In 1981, production totaled 54.3 million cords with softwood roundwood accounting for about 50 percent, hardwood roundwood 18 percent, and mill byproducts 32 percent.

  11. Equipment & New Products.

    ERIC Educational Resources Information Center

    Poitras, Adrian W., Ed.

    1979-01-01

    Reviews new science equipment and products for the laboratory. Includes hand-held calculators, fiberglass fume hoods, motorized microtomy, disposable mouse cages, and electric timers. Describes 11 products total. Provides manufacturer name, address, and price. (MA)

  12. The Top 10 Products

    ERIC Educational Resources Information Center

    American School & University, 2008

    2008-01-01

    In 2008, American School & University showcased some of the hottest products in the industry. This article presents the 10 most requested, as determined by readers. Products include fluorescent lighting, concrete floor maintenance and exterior sheathing.

  13. The Top 10 Products

    ERIC Educational Resources Information Center

    American School & University, 2008

    2008-01-01

    In 2008, American School & University showcased some of the hottest products in the industry. This article presents the 10 most requested, as determined by readers. Products include fluorescent lighting, concrete floor maintenance and exterior sheathing.

  14. Choosing Safe Baby Products

    MedlinePlus

    ... to Be Smart About Social Media Choosing Safe Baby Products KidsHealth > For Parents > Choosing Safe Baby Products Print A A A Even though babies are small and seem uncomplicated, there's nothing small ...

  15. Equipment & New Products.

    ERIC Educational Resources Information Center

    Poitras, Adrian W., Ed.

    1979-01-01

    Reviews new science equipment and products for the laboratory. Includes hand-held calculators, fiberglass fume hoods, motorized microtomy, disposable mouse cages, and electric timers. Describes 11 products total. Provides manufacturer name, address, and price. (MA)

  16. Pesticide Product Label System

    EPA Pesticide Factsheets

    The Pesticide Product Label System (PPLS) provides a collection of pesticide product labels (Adobe PDF format) that have been approved by EPA under Section 3 of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA). New labels were added to PPLS on November 21, 2014. Pesticide product labels provide critical information about how to safely handle and use registered pesticide products. An approved pesticide product label represents the full content of EPAs registration decision regarding that product. Pesticide labels contain detailed information on the use, storage, and handling of a product. This information will be found on EPA stamped-approved labels and, in some cases, in subsequent related correspondence, which is also included in PPLS. You may need to review several PDF files for a single product to determine the complete current terms of registration.

  17. Southern pulpwood production, 2005

    Treesearch

    Tony G. Johnson; Carolyn D. Steppleton

    2007-01-01

    Southern pulpwood production was 64.0 million cords in 2005, up from 63.8 million cords in 2004. Roundwood production declined 2 percent to 46.2 million cords in 2005 and accounted for 72 percent of the total pulpwood production. The use of wood residue increased 6 percent to 17.8 million cords. Alabama led the South in total production at 10.2 million cords. In 2005,...

  18. Southern pulpwood production, 2002

    Treesearch

    Tony G. Johnson; Carolyn D. Steppleton

    2004-01-01

    In 2002, the South's production of pulpwood showed a slight increase: from 63.5 million cords in 2001 to 63.8 million cords. Roundwood production dropped to 42.1 million cords and accounted for 66 percent of the total pulpwood production. The use of wood residue increased 2 percent to 21.7 million cords. Alabama continued to lead the South in total production and...

  19. Southern pulpwood production, 2001

    Treesearch

    Tony G. Johnson; Carolyn D. Steppleton

    2003-01-01

    In 2001, the South’s production of pulpwood declined 5 percent to 63.5 million cords. Roundwood production dropped to 42.3 million cords and accounted for 67 percent of the total pulpwood production. The use of wood residue declined 5 percent to 21.2 million cords. Alabama continued to lead the South in total production and number of mills. In 2001, 94 mills were...

  20. Southern pulpwood production, 2000

    Treesearch

    Tony G. Johnson; Carolyn D. Steppleton

    2002-01-01

    In 2000, the South’s production of pulpwood declined 6 percent to 66.6 million cords. Roundwood production dropped to 44.4 million cords and accounted for 67 percent of the total pulpwood production. The use of wood residue increased 2 percent to 22.3 million cords. Alabama continued to lead the South in total production, number of mills, and pulping capacity. In 2000...

  1. Southern pulpwood production, 2003

    Treesearch

    Tony G. Johnson; Carolyn D. Steppleton

    2005-01-01

    The South’s production of pulpwood declined from 63.8 million cords in 2002 to 61.3 million cords in 2003. Roundwood production increased 5 percent to 44.3 million cords and accounted for 72 percent of the total pulpwood production. The use of wood residue dropped 22 percent to 17.0 million cords. Georgia led the South in total production at 9.7 million cords. In 2003...

  2. Human productivity program definition

    NASA Technical Reports Server (NTRS)

    Cramer, D. B.

    1985-01-01

    The optimization of human productivity on the space station within the existing resources and operational constraints is the aim of the Human Productivity Program. The conceptual objectives of the program are as follows: (1) to identify long lead technology; (2) to identify responsibility for work elements; (3) to coordinate the development of crew facilities and activities; and (4) to lay the foundation for a cost effective approach to improving human productivity. Human productivity work elements are also described and examples are presented.

  3. Southern pulpwood production, 2004

    Treesearch

    Tony G. Johnson; Carolyn D. Steppleton

    2006-01-01

    In 2004, the South's production of pulpwood increased from 61.3 million cords in 2003 to 63.8 million cords. Roundwood production increased 6 percent to 47.0 million cords and accounted for 74 percent of the total pulpwood production. The use of wood residue declined 1 percent to 16.8 million cords. Alabama led the South in total production at 10.2 million cords....

  4. Southern pulpwood production, 2006

    Treesearch

    Tony G. Johnson; Carolyn D. Steppleton

    2008-01-01

    The South's production of pulpwood increased from 64.0 million cords in 2005 to 64.7 million cords in 2006. Roundwood production increased 123,300 cords to 46.3 million cords and accounted for 72 percent of the total pulpwood production. The use of wood residue increased 3 percent to 18.3 million cords. Alabama led the South in total production at 10.5 million...

  5. Southern pulpwood production, 1985

    Treesearch

    Cecil C. Hutchins

    1987-01-01

    Total pulpwood production in the South declined 3 percent since 1984. After a record high of 58.7 million cords in 1984, only 56.9 million cords were produced during a 1985 (Table 1). Production \\tof softwood roundwood, hardwood roundwood and hardwood resudiues declined, whereas production of softwood residues remained constant. Three pulpmills closed during the year,...

  6. Container hardwood seedling production

    Treesearch

    John McRae

    2005-01-01

    Container production of hardwood seedlings requires larger cavities, more space, and the ability to easily sort seedlings (as compared to conifers) very early during the germination phase of production. This presentation demonstrates the most productive system, based upon past experience, to commercially produce container hardwoods. The container system of choice is...

  7. MOPITT Product Descriptions

    Atmospheric Science Data Center

    2017-04-03

    ... Product Descriptions " (PDF).   T (Thermal or TIR):       Uses the instrument's thermal infrared channels and is most ... team members to exploit it properly. Compared to earlier TIR-based MOPITT products, this product exhibits larger random errors and may ...

  8. Nulcear materials production: Primer

    SciTech Connect

    Not Available

    1988-09-01

    The US Department of Energy's (DOE's) Office of Nuclear Materials Production (NMP) is responsible for managing the production and recovery of nuclear materials for national defense. NMP oversees the production of radioactive materials for government, commercial, industrial, and medical applications. This Primer is a general introduction to NMP's major activities.

  9. Pomegranate production and marketing

    USDA-ARS?s Scientific Manuscript database

    This book is relatively short, with 134 pages, 15 chapters, 52 figures, and 20 tables. It ranges from cultivar descriptions, production, biotic and abiotic challenges to production, to postharvest, aril and juice production, health benefits, and international trade. It contains great information and...

  10. The EGRET data products

    NASA Technical Reports Server (NTRS)

    Mattox, J. R.; Bertsch, D. L.; Fichtel, C. E.; Hartman, R. C.; Hunter, S. D.; Kanbach, G.; Kniffen, D. A.; Kwok, P. W.; Lin, Y. C.; Mayer-Hasselwander, H. A.

    1992-01-01

    We describe the Energetic Gamma Ray Experiment Telescope (EGRET) data products which we anticipate will suffice for virtually all guest and archival investigations. The production process, content, availability, format, and the associated software of each product is described. Supplied here is sufficient detail for each researcher to do analysis which is not supported by extant software.

  11. Reconstituted products from oak

    Treesearch

    W. C. Lewis; B. G. Heebink

    1971-01-01

    "Reconstituted" describes a family of panel products made from fractionated oak, bonded with either a synthetic resin or a natural lignin bond. Several current commercial fiber panel products from oak are described, and the status of research on experimental products and processes is presented. Recent technological developments are removing the stigma...

  12. Southern pulpwood production, 1990

    Treesearch

    John S. Vissage; Patrick E. Miller

    1992-01-01

    In 1990, Southern pulpwood production exceeded 65 million cords, roundwood production increased 9 percent to 45.6 million cords, and wood residue production increased 2 percent to 19.4 million cords. The pulping capacity of the 103 Southern pulpmills was 129,290 tons per day. One pulpmill was under construction.

  13. Southern pulpwood production, 1992

    Treesearch

    Patrick E. Miller

    1994-01-01

    In 1992, southern pulpwood production increased 4 percent to 67.9 million cords. Roundwood production increased 1 percent to 47.3 million cords, and wood residue production increased 12 percent to 20.7 million cords. One pulpmill changed processes, reducing the number to 103. The pulping capacity of the 103 southern pulpmills was 133,400 tons per day. No new...

  14. Vocational Education and Productivity.

    ERIC Educational Resources Information Center

    Watson, Robert, Jr.

    Vocational education can contribute to an improved United States productivity by producing an effective work force. People together with technology are two major factors in improving productivity, and they must be integrated. Industry is in the forefront of the efforts to improve productivity. It has encouraged management in long-range strategic…

  15. Coal production 1989

    SciTech Connect

    Not Available

    1990-11-29

    Coal Production 1989 provides comprehensive information about US coal production, the number of mines, prices, productivity, employment, reserves, and stocks to a wide audience including Congress, federal and state agencies, the coal industry, and the general public. 7 figs., 43 tabs.

  16. Measuring nurse practitioner productivity.

    PubMed

    Rhoads, Jacqueline; Ferguson, Laurie Anne; Langford, Cynthia A

    2006-02-01

    As the role of the nurse practitioner (NP) evolves, the need to demonstrate productivity becomes more important. Productivity data provides NPs with practice statistics to generate business or use in contract negotiations with potential clients such as employers, managed care organizations, and insurance companies. However, beyond the numbers of patients seen per day or amount of reimbursement a provider brings to the practice, NPs may provide additional benefit that is not captured with physician productivity measures. Information to acquaint NPs with key aspects of recording productivity and ways NPs can organize productivity data within their practice to determine worth of service are presented.

  17. IT product competition Network

    NASA Astrophysics Data System (ADS)

    Xu, Xiu-Lian; Zhou, Lei; Shi, Jian-Jun; Wang, Yong-Li; Feng, Ai-Xia; He, Da-Ren

    2008-03-01

    Along with the technical development, the IT product competition becomes increasingly fierce in recent years. The factories, which produce the same IT product, have to improve continuously their own product quality for taking a large piece of cake in the product sale market. We suggest using a complex network description for the IT product competition. In the network the factories are defined as nodes, and two nodes are connected by a link if they produce a common IT product. The edge represents the sale competition relationship. 2121 factories and 265 products have been investigated. Some statistical properties, such as the degree distribution, node strength distribution, assortativity, and node degree correlation have been empirically obtained.

  18. Economics of stocker production.

    PubMed

    Peel, Derrell S

    2006-07-01

    The beef cattle industry, like any industry, is subject to economic signals to increase or decrease production according to short-run and long-run market conditions. Profitable stocker production is the result of careful matching of economic conditions to alternative animal production systems combined with sound animal and business management. The economics of stocker production are driven by the feeder cattle price-weight relation that combines broad market signals about how much production is needed with complex and subtle signals about how that production should be accomplished. The result is a dynamic set of values of gain that direct producers to adjust the level, type, and timing of stocker production according to changing market conditions.

  19. 43 CFR 3931.70 - Production maps and production reports.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 43 Public Lands: Interior 2 2011-10-01 2011-10-01 false Production maps and production reports... EXPLORATION AND LEASES Plans of Development and Exploration Plans § 3931.70 Production maps and production reports. (a) Report production of all oil shale products or by-products to the BLM on a quarterly basis...

  20. Fermentative production of isobutene.

    PubMed

    van Leeuwen, Bianca N M; van der Wulp, Albertus M; Duijnstee, Isabelle; van Maris, Antonius J A; Straathof, Adrie J J

    2012-02-01

    Isobutene (2-methylpropene) is one of those chemicals for which bio-based production might replace the petrochemical production in the future. Currently, more than 10 million metric tons of isobutene are produced on a yearly basis. Even though bio-based production might also be achieved through chemocatalytic or thermochemical methods, this review focuses on fermentative routes from sugars. Although biological isobutene formation is known since the 1970s, extensive metabolic engineering is required to achieve economically viable yields and productivities. Two recent metabolic engineering developments may enable anaerobic production close to the theoretical stoichiometry of 1isobutene + 2CO(2) + 2H(2)O per mol of glucose. One relies on the conversion of 3-hydroxyisovalerate to isobutene as a side activity of mevalonate diphosphate decarboxylase and the other on isobutanol dehydration as a side activity of engineered oleate hydratase. The latter resembles the fermentative production of isobutanol followed by isobutanol recovery and chemocatalytic dehydration. The advantage of a completely biological route is that not isobutanol, but instead gaseous isobutene is recovered from the fermenter together with CO(2). The low aqueous solubility of isobutene might also minimize product toxicity to the microorganisms. Although developments are at their infancy, the potential of a large scale fermentative isobutene production process is assessed. The production costs estimate is 0.9 Euro kg(-1), which is reasonably competitive. About 70% of the production costs will be due to the costs of lignocellulose hydrolysate, which seems to be a preferred feedstock.

  1. Measuring a product's usefulness.

    PubMed

    Aubin, Francois; Atoyan, Hasmik; Robert, Jean-Marc; Atoyan, Tigran

    2012-01-01

    This paper explains how a product's usefulness may be defined and measured. Many aspects of consumer product assessments are conducted sub-consciously and this process is closely examined. A product's usefulness can be evaluated by measuring its advantages over alternative solutions based on specific criteria associated with fundamentals needs. When multiple criteria are involved, different weights are assigned to each. It should take into account the context in which the product is used. For the purpose of this paper, we use a formula to determine the relative usefulness of a variety of products in different contexts. We conclude that aspects of product's usefulness, connected with sub-conscious human decision making processes, can be a major factor in predicting acceptance and rejection rates.

  2. Coal Production 1992

    SciTech Connect

    Not Available

    1993-10-29

    Coal Production 1992 provides comprehensive information about US coal production, the number of mines, prices, productivity, employment, productive capacity, and recoverable reserves to a wide audience including Congress, Federal and State agencies, the coal industry, and the general public. In 1992, there were 3,439 active coal mining operations made up of all mines, preparation plants, and refuse operations. The data in Table 1 cover the 2,746 mines that produced coal, regardless of the amount of production, except for bituminous refuse mines. Tables 2 through 33 include data from the 2,852 mining operations that produced, processed, or prepared 10 thousand or more short tons of coal during the period, except for bituminous refuse, and includes preparation plants with 5 thousand or more employee hours. These mining operations accounted for over 99 percent of total US coal production and represented 83 percent of all US coal mining operations in 1992.

  3. Estimating Prices of Products

    NASA Technical Reports Server (NTRS)

    Aster, R. W.; Chamberlain, R. G.; Zendejas, S. C.; Lee, T. S.; Malhotra, S.

    1986-01-01

    Company-wide or process-wide production simulated. Price Estimation Guidelines (IPEG) program provides simple, accurate estimates of prices of manufactured products. Simplification of SAMIS allows analyst with limited time and computing resources to perform greater number of sensitivity studies. Although developed for photovoltaic industry, readily adaptable to standard assembly-line type of manufacturing industry. IPEG program estimates annual production price per unit. IPEG/PC program written in TURBO PASCAL.

  4. Coal combustion products

    USGS Publications Warehouse

    Kalyoncu, R.S.; Olson, D.W.

    2001-01-01

    Coal-burning powerplants, which supply more than half of U.S. electricity, also generate coal combustion products, which can be both a resource and a disposal problem. The U.S. Geological Survey collaborates with the American Coal Ash Association in preparing its annual report on coal combustion products. This Fact Sheet answers questions about present and potential uses of coal combustion products.

  5. Infrastructure for microsystem production

    NASA Astrophysics Data System (ADS)

    van Heeren, Henne; Sanchez, Stefan; Elders, Job; Heideman, Rene G.

    1999-03-01

    Manufacturing of micro-systems differs from IC manufacturing because the market requires a diversity of products and lower volumes per product. In addition, a diversity of micro-technologies has been developed, including non-IC compatible processes and potentially IC compatible processes. An infrastructure for the production of micro- system devices is lacking. On one side the technology for MST is available at the universities and small university related companies. On the other side there are several small and medium enterprises and bigger companies wanting to implement MST devices in their products, but unwilling to be dependent on universities. Philips Electronics in the Netherlands and Twente MicroProducts realized this problem and have started a project to fill this gap. At this moment the basic of the infrastructure is available: OnStream BV, Eindhoven, The Netherlands, opened its waferfab and assembly facilities for the production of MST devices. Twente MicroProducts will take care of the design of the products and of the small-scale production. Integration of quality systems for maintenance, yield, statistical process control and production in a Manufacturing Execution System offers direct access for all people involved to all the relevant information. It also ensures quality of the products made. The available capabilities of the infrastructure in the current status are compared to the market needs. In this article, a description of a seamless Micro-System Engineering Foundry is given. A seamless organization is capable of helping the customer from design to production. Several examples are given.

  6. Southern pulpwood production, 2011

    Treesearch

    James W. Bentley; Carolyn D. Steppleton

    2013-01-01

    The South’s production of pulpwood declined from 65.5 million cords in 2010 to 62.7 million cords in 2011. Roundwood production decreased by 878,000 cords to 50.1 million cords and accounted for 80 percent of the South’s total pulpwood production. The use of wood residue dropped 14 percent to 12.6 million cords in 2011. Georgia and Alabama led the South in total...

  7. Microbial production of epoxides

    DOEpatents

    Clark, Thomas R.; Roberto, Francisco F.

    2003-06-10

    A method for microbial production of epoxides and other oxygenated products is disclosed. The method uses a biocatalyst of methanotrophic bacteria cultured in a biphasic medium containing a major amount of a non-aqueous polar solvent. Regeneration of reducing equivalents is carried out by using endogenous hydrogenase activity together with supplied hydrogen gas. This method is especially effective with gaseous substrates and cofactors that result in liquid products.

  8. Nasa's Emerging Productivity Program

    NASA Technical Reports Server (NTRS)

    Braunstein, D. R.

    1984-01-01

    The goals, membership, and organizational structure of the NASA Productivity Steering Committee are described as well as steps taken to make NASA a leader in the development and application of productivity and quality concepts at every level of agency management. The overall strategy for the Productivity Improvement and Quality Enhancement (PIQE) Program is through employee involvement, both civil servant and contractor, in all phases of agency-wide activity. Elements of the PIQE program and initial thrusts are examined.

  9. Diboson production (CDF)

    SciTech Connect

    Cavaliere, Viviana; /Siena U. /INFN, Siena

    2009-01-01

    WW and WZ production in p{bar p} collisions at 1.96 TeV are studied in samples of {approx}3 fb{sup -1} of data using leptons, jets and missing E{sub T}. Fully leptonic decays as well as semi-leptonic decays are measured. Diboson production is expected in the standard model, and predicted cross sections are confirmed. It is important to investigate various signatures as associated production of Higgs bosons is topologically similar.

  10. Estimating Prices of Products

    NASA Technical Reports Server (NTRS)

    Aster, R. W.; Chamberlain, R. G.; Zendejas, S. C.; Lee, T. S.; Malhotra, S.

    1986-01-01

    Company-wide or process-wide production simulated. Price Estimation Guidelines (IPEG) program provides simple, accurate estimates of prices of manufactured products. Simplification of SAMIS allows analyst with limited time and computing resources to perform greater number of sensitivity studies. Although developed for photovoltaic industry, readily adaptable to standard assembly-line type of manufacturing industry. IPEG program estimates annual production price per unit. IPEG/PC program written in TURBO PASCAL.

  11. Nanotechnology in cosmetic products.

    PubMed

    Epstein, Howard A

    2011-01-01

    Nanotechnology is a subject of extensive global interest. The ability to control matter at the nanoscale level presents a revolutionary opportunity to benefit society in numerous disciplines. Nanotechnology is currently found in cosmetic products, particularly sunscreen products containing titanium dioxide and zinc oxide. Published information in scientific journals suggests that nano-sized ingredients used in cosmetic products pose no more risk to human health than larger sized counterparts. The issue remains under investigation.

  12. Sustainable hydrogen production

    SciTech Connect

    Block, D.L.; Linkous, C.; Muradov, N.

    1996-01-01

    This report describes the Sustainable Hydrogen Production research conducted at the Florida Solar Energy Center (FSEC) for the past year. The report presents the work done on the following four tasks: Task 1--production of hydrogen by photovoltaic-powered electrolysis; Task 2--solar photocatalytic hydrogen production from water using a dual-bed photosystem; Task 3--development of solid electrolytes for water electrolysis at intermediate temperatures; and Task 4--production of hydrogen by thermocatalytic cracking of natural gas. For each task, this report presents a summary, introduction/description of project, and results.

  13. TRMM Gridded Text Products

    NASA Technical Reports Server (NTRS)

    Stocker, Erich Franz

    2007-01-01

    NASA's Tropical Rainfall Measuring Mission (TRMM) has many products that contain instantaneous or gridded rain rates often among many other parameters. However, these products because of their completeness can often seem intimidating to users just desiring surface rain rates. For example one of the gridded monthly products contains well over 200 parameters. It is clear that if only rain rates are desired, this many parameters might prove intimidating. In addition, for many good reasons these products are archived and currently distributed in HDF format. This also can be an inhibiting factor in using TRMM rain rates. To provide a simple format and isolate just the rain rates from the many other parameters, the TRMM product created a series of gridded products in ASCII text format. This paper describes the various text rain rate products produced. It provides detailed information about parameters and how they are calculated. It also gives detailed format information. These products are used in a number of applications with the TRMM processing system. The products are produced from the swath instantaneous rain rates and contain information from the three major TRMM instruments: radar, radiometer, and combined. They are simple to use, human readable, and small for downloading.

  14. Production readiness verification testing

    NASA Technical Reports Server (NTRS)

    James, A. M.; Bohon, H. L.

    1980-01-01

    A Production Readiness Verification Testing (PRVT) program has been established to determine if structures fabricated from advanced composites can be committed on a production basis to commercial airline service. The program utilizes subcomponents which reflect the variabilities in structure that can realistically be expected from current production and quality control technology to estimate the production qualities, variation in static strength, and durability of advanced composite structures. The results of the static tests and a durability assessment after one year of continuous load/environment testing of twenty two duplicates of each of two structural components (a segment of the front spar and cover of a vertical stabilizer box structure) are discussed.

  15. Cleaning Products Pilot Project

    EPA Pesticide Factsheets

    This 1997 case study documents a three-year effort to identify and compare environmentally preferable commercial cleaning products and to implement the Environmentally Preferable Purchasing Program (EPP).

  16. Recombinant organisms for production of industrial products

    PubMed Central

    Adrio, Jose-Luis

    2010-01-01

    A revolution in industrial microbiology was sparked by the discoveries of ther double-stranded structure of DNA and the development of recombinant DNA technology. Traditional industrial microbiology was merged with molecular biology to yield improved recombinant processes for the industrial production of primary and secondary metabolites, protein biopharmaceuticals and industrial enzymes. Novel genetic techniques such as metabolic engineering, combinatorial biosynthesis and molecular breeding techniques and their modifications are contributing greatly to the development of improved industrial processes. In addition, functional genomics, proteomics and metabolomics are being exploited for the discovery of novel valuable small molecules for medicine as well as enzymes for catalysis. The sequencing of industrial microbal genomes is being carried out which bodes well for future process improvement and discovery of new industrial products. PMID:21326937

  17. Recombinant organisms for production of industrial products.

    PubMed

    Adrio, Jose-Luis; Demain, Arnold L

    2010-01-01

    A revolution in industrial microbiology was sparked by the discoveries of ther double-stranded structure of DNA and the development of recombinant DNA technology. Traditional industrial microbiology was merged with molecular biology to yield improved recombinant processes for the industrial production of primary and secondary metabolites, protein biopharmaceuticals and industrial enzymes. Novel genetic techniques such as metabolic engineering, combinatorial biosynthesis and molecular breeding techniques and their modifications are contributing greatly to the development of improved industrial processes. In addition, functional genomics, proteomics and metabolomics are being exploited for the discovery of novel valuable small molecules for medicine as well as enzymes for catalysis. The sequencing of industrial microbal genomes is being carried out which bodes well for future process improvement and discovery of new industrial products.

  18. Accountability for Productivity

    ERIC Educational Resources Information Center

    Wellman, Jane

    2010-01-01

    Productivity gains in higher education won't be made just by improving cost effectiveness or even performance. They need to be documented, communicated, and integrated into a strategic agenda to increase attainment. This requires special attention to "accountability" for productivity, meaning public presentation and communication of evidence about…

  19. Pensions and Productivity.

    ERIC Educational Resources Information Center

    Dorsey, Stuart; Cornwell, Christopher; Macpherson, David

    This book analyzes the productivity theory of pensions. First, it reviews the history and institutional practices of private pensions and government policy. Chapter 1 discusses demand-side and supply-side perspectives on pensions, the significance of the productivity theory of pensions, and the organization of this book. Chapter 2 traces origins…

  20. Equipment & New Products.

    ERIC Educational Resources Information Center

    Poitras, Adrian W., Ed.

    1977-01-01

    Presents several new products and equipment for teaching college science courses such as laser optics bench, portable digital thermometer, solar energy furnaces and blackboard optics kit. A description of all equipment or products, cost, and addresses of manufacturers are also included. (HM)

  1. Training for Productivity.

    ERIC Educational Resources Information Center

    Maglen, Leo; Hopkins, Sonnie; Burke, Gerald

    An exploratory study was conducted to evaluate the utility of a method to demonstrate that Australian enterprises that invest in the training of their employees gain a return from that investment through an increase in employee productivity. The method, which compares enterprise expenditure on training of personnel with labor productivity across a…

  2. Southern pulpwood production, 1977

    Treesearch

    Thomas R. Bellamy

    1978-01-01

    Southern pulpwood production increased 3 percent in 1977 to 48.9 million cords. Roundwood production increased slightly while use of plant byproducts rose 9 percent. The use of plant byproducts continues to increase and now contributes 34 percent of the total. Pulping capacity increased to 100,894 tons per day.

  3. Productivity and Capital Goods.

    ERIC Educational Resources Information Center

    Zicht, Barbara, Ed.; And Others

    1981-01-01

    Providing teacher background on the concepts of productivity and capital goods, this document presents 3 teaching units about these ideas for different grade levels. The grade K-2 unit, "How Do They Do It?," is designed to provide students with an understanding of how physical capital goods add to productivity. Activities include a field trip to…

  4. Oblique warped products

    NASA Astrophysics Data System (ADS)

    Bejancu, Aurel

    2007-02-01

    We define the oblique warped products and prove their existence. In addition to the Levi-Civita connection we use both the Schouten Van Kampen and Vrănceanu connections to study the foliation and curvatures of an oblique warped product. As an application to cosmology we introduce the oblique Robertson Walker spacetime and give its basic properties.

  5. OSI Product Survey.

    ERIC Educational Resources Information Center

    Metka, Tonia

    1990-01-01

    Reviews some of the projects and organizations concerned with promoting conformance and interoperability testing of Open Systems Interconnection (OSI) products and describes OSI products available from computer manufacturers and vendors. A list of references includes 57 articles that mention specific vendors and 11 general articles about OSI…

  6. Medical School Faculty Productivity

    ERIC Educational Resources Information Center

    Pearse, Warren; And Others

    1976-01-01

    Faculty productivity as measured by publication for the Medical College of Virginia School of Medicine was computed and compared to that of Ph.D.'s in laboratories stressing scientific publication, as reported in previous research. A similar bimodal productivity by age was found for clinical faculty in the medical school setting. (JT)

  7. Ethyl alcohol production

    SciTech Connect

    Hofman, V.; Hauck, D.

    1980-11-01

    Recent price increases and temporary shortages of petroleum products have caused farmers to search for alternate sources of fuel. The production of ethyl alcohol from grain is described and the processes involved include saccharification, fermentation and distillation. The resulting stillage has potential as a livestock feed.

  8. MICROBIAL RESISTANT GYPSUM PRODUCTS

    EPA Science Inventory

    Gypsum building materials often become wet, resulting in mold growth that leads to health and productivity impacts. A major source of mold growth is gypsum wallboard since nearly 90% of the interior finished surfaces of buildings are covered with gypsum products. It has been est...

  9. Training for Productivity.

    ERIC Educational Resources Information Center

    Maglen, Leo; Hopkins, Sonnie; Burke, Gerald

    An exploratory study was conducted to evaluate the utility of a method to demonstrate that Australian enterprises that invest in the training of their employees gain a return from that investment through an increase in employee productivity. The method, which compares enterprise expenditure on training of personnel with labor productivity across a…

  10. Equipment & New Products.

    ERIC Educational Resources Information Center

    Poitras, Adrian W., Ed.

    1977-01-01

    Presents information about equipment and new products such as the melting point instrument and TV-microscope coupler which are helpful in college science teaching. Descriptions of each product, how it operates, its prices, and address for ordering are presented. (HM)

  11. Equipment & New Products.

    ERIC Educational Resources Information Center

    Poitras, Adrian W., Ed.

    1977-01-01

    Presents several new products and equipment for teaching college science courses such as laser optics bench, portable digital thermometer, solar energy furnaces and blackboard optics kit. A description of all equipment or products, cost, and addresses of manufacturers are also included. (HM)

  12. Software Product Lines Essentials

    DTIC Science & Technology

    2008-07-01

    improvement Technology innovation Reuse 7 Software Product Lines Linda Northrop © 2008 Carnegie Mellon University Few Systems Are Unique Most...Focus was small-grained, opportunistic, and technology -driven. Results did not meet business goals. Reuse History 9 Software Product Lines Linda...servers, storage servers, network camera and scanner servers Bold Stroke Avionics Customized solutions for transportation industries E-COM Technology

  13. MICROBIAL RESISTANT GYPSUM PRODUCTS

    EPA Science Inventory

    Gypsum building materials often become wet, resulting in mold growth that leads to health and productivity impacts. A major source of mold growth is gypsum wallboard since nearly 90% of the interior finished surfaces of buildings are covered with gypsum products. It has been est...

  14. Insect mass production technologies

    USDA-ARS?s Scientific Manuscript database

    Insects provide a very promising alternative for the future production of animal protein. Their nutritional value in conjunction with their food conversion efficiency and low water requirements, make them a more sustainable choice for the production of food and animal origin. However, to realize the...

  15. Research Productivity and Tenure.

    ERIC Educational Resources Information Center

    McNurlen, Brian; West, Charles K.

    This study examined research productivity over the course of the professional career and its relationship with tenure. It hypothesized that the rate of scholarly productivity does not decrease after tenure, and further, that the amount of activity of older faculty is comparable to new faculty. Data were collected from the curriculum vitae of…

  16. User Oriented Product Evaluation.

    ERIC Educational Resources Information Center

    Alkin, Marvin C.; Wingard, Joseph

    While the educational product development field has expanded tremendously over the last 15 years, there is a paucity of conveniently assembled and readily interpretable information that would enable users to make accurate and informed evaluations of different, but comparable, instructional products. Minimum types of validation data which should be…

  17. Process to Product.

    ERIC Educational Resources Information Center

    Harrison, Gary, Ed.; Mirkes, Donna Z., Ed.

    Intended for educators who direct federally funded model projects, the booklet provides a framework for special education product development. In "Making Media Decisions," G. Richman explores procedures for selecting the most appropriate medium to carry the message of a given product. The fundamental questions are addressed: what is the goal; who…

  18. Equipment & New Products.

    ERIC Educational Resources Information Center

    Poitras, Adrian W., Ed.

    1977-01-01

    Presents information about equipment and new products such as the melting point instrument and TV-microscope coupler which are helpful in college science teaching. Descriptions of each product, how it operates, its prices, and address for ordering are presented. (HM)

  19. 1962 Washington log production.

    Treesearch

    Richard L. Nielsen

    1963-01-01

    Washington's 1962 log production reached 5.05 billion board feet. This is an increase of 14 percent, or 616 million board feet, over 1961 and the highest total log production since the 1941 figure of 5.14 billion board feet.

  20. Products from lunar anorthite

    NASA Technical Reports Server (NTRS)

    Anthony, Donald L.; Cochran, C. Norman; Cochran, William C.; Haupin, Warren E.; Keller, Rudolph

    1989-01-01

    Lunar anorthositic soil can be processed to produce oxygen, silicon, aluminum, and calcium. A process scheme starting with the beneficiation of the ore by magnetic separation and yielding the pure products is being developed. Simplifications in the process are possible if requirements regarding product purity and separation may be relaxed.

  1. Biotechnology and derived products

    USDA-ARS?s Scientific Manuscript database

    Microorganisms able to infect and kill insect pests, metabolites from plants and microorganisms, and transgenic crops are biotechnologically derived products that are being promoted for use to control insect pests in lieu of chemical insecticides. Products based on these technologies effectively co...

  2. Rice Production and Marketing.

    ERIC Educational Resources Information Center

    Briers, Gary; Lee, Jasper S.

    This guide contains lesson plans for use in secondary programs of agricultural education in geographical areas in which rice is produced. Six units and 13 problem areas are organized into teaching plans that cover the broad nature of rice production. The six units are: (1) determining the importance and history of rice production; (2) determining…

  3. Forest products issue.

    Treesearch

    Thornton T. Munger

    1935-01-01

    This issue of Forest Research Notes is devoted to abstracts of projects under way or recently completed by the Section of Forest Products. This section conducts research designed to contribute to better and more economic utilization of the products of the forest. As shown by the variety of subjects presented in these notes, the projects range from the statistics of...

  4. Central Exclusive Dijet Production

    SciTech Connect

    Dechambre, A.; Cudell, J. R.; Ivanov, I. P.; Hernandez, O.

    2008-08-29

    The ingredients of central exclusive production cross section include large perturbative corrections and soft quantities that must be parametrized and fitted to data. In this talk, we summarize the results of a study of the uncertainties coming from these ingredients, in the case of exclusive dijet production.

  5. Productivity: An Overview.

    ERIC Educational Resources Information Center

    Swartz, Carl

    This training package explains productivity in terms of the difference between worker output and company input. Output is defined in terms of the products and/or services of an organization (number and/or quality of units produced, efficiency of time use, marginal profits) and in terms of behavior (labor turnover, disruptions in routine, wasted…

  6. Process, Product, and Playmaking

    ERIC Educational Resources Information Center

    Fisher, Maisha T.; Purcell, Susie Spear; May, Rachel

    2009-01-01

    This article examines relationships among process, product, and playmaking in a southeastern playwriting and performance program for teen girls, Playmaking for Girls (PFG). The authors have chosen to focus on tensions between process and product. Such tensions are present in the challenges teachers experience when privileging student-centered…

  7. Management Attitudes toward Productivity.

    ERIC Educational Resources Information Center

    Chamber of Commerce of the United States, Washington, DC.

    In an attempt to discover management attitudes toward productivity, including management's views about worker attitudes and their motivation, managerial practices and organization, and possible changes to effect improvements in productivity, the United States Chamber of Commerce surveyed a sample of 1,870 top business executives across the country…

  8. The Productivity Conundrum.

    ERIC Educational Resources Information Center

    Green, Kenneth C.

    2000-01-01

    Examines issues of quality in higher education in relation to economic concepts of productivity. Suggests that the debate between definitions of productivity that focus on costs and traditional concepts of quality may affect policy decisions in how campuses use information technology. (DB)

  9. Productivity and Capital Goods.

    ERIC Educational Resources Information Center

    Zicht, Barbara, Ed.; And Others

    1981-01-01

    Providing teacher background on the concepts of productivity and capital goods, this document presents 3 teaching units about these ideas for different grade levels. The grade K-2 unit, "How Do They Do It?," is designed to provide students with an understanding of how physical capital goods add to productivity. Activities include a field trip to…

  10. Questionnaire typography and production.

    PubMed

    Gray, M

    1975-06-01

    This article describes the typographic principles and practice which provide the basis of good design and print, the relevant printing processes which can be used, and the graphic designer's function in questionnaire production. As they impose constraints on design decisions to be discussed later in the text, the various methods of printing and production are discussed first.

  11. Southern pulpwood production, 1980

    Treesearch

    Victor A. Rudis

    1980-01-01

    Total southern pulpwood production in 1980 was 54.5 million cords, an amount comparable to the 54.3 million cords reported in 1979. This slower growth is in marked contrast to the 3 to 12 percent growth which occurred in the years since 1975 (fig. 1). Softwood roundwood continues to be the most important contributor to annual production.

  12. Drilling Productivity Report

    EIA Publications

    2017-01-01

    Energy Information Administration’s (EIA) new Drilling Productivity Report (DPR) takes a fresh look at oil and natural gas production, starting with an assessment of how and where drilling for hydrocarbons is taking place. The DPR uses recent data on the total number of drilling rigs in operation along with estimates of drilling productivity and estimated changes in production from existing oil and natural gas wells to provide estimated changes in oil and natural gas production for six key fields. EIA's approach does not distinguish between oil-directed rigs and gas-directed rigs because once a well is completed it may produce both oil and gas; more than half of the wells produce both.

  13. Hydrogen production by Cyanobacteria.

    PubMed

    Dutta, Debajyoti; De, Debojyoti; Chaudhuri, Surabhi; Bhattacharya, Sanjoy K

    2005-12-21

    The limited fossil fuel prompts the prospecting of various unconventional energy sources to take over the traditional fossil fuel energy source. In this respect the use of hydrogen gas is an attractive alternate source. Attributed by its numerous advantages including those of environmentally clean, efficiency and renew ability, hydrogen gas is considered to be one of the most desired alternate. Cyanobacteria are highly promising microorganism for hydrogen production. In comparison to the traditional ways of hydrogen production (chemical, photoelectrical), Cyanobacterial hydrogen production is commercially viable. This review highlights the basic biology of cynobacterial hydrogen production, strains involved, large-scale hydrogen production and its future prospects. While integrating the existing knowledge and technology, much future improvement and progress is to be done before hydrogen is accepted as a commercial primary energy source.

  14. Hydrogen production by Cyanobacteria

    PubMed Central

    Dutta, Debajyoti; De, Debojyoti; Chaudhuri, Surabhi; Bhattacharya, Sanjoy K

    2005-01-01

    The limited fossil fuel prompts the prospecting of various unconventional energy sources to take over the traditional fossil fuel energy source. In this respect the use of hydrogen gas is an attractive alternate source. Attributed by its numerous advantages including those of environmentally clean, efficiency and renew ability, hydrogen gas is considered to be one of the most desired alternate. Cyanobacteria are highly promising microorganism for hydrogen production. In comparison to the traditional ways of hydrogen production (chemical, photoelectrical), Cyanobacterial hydrogen production is commercially viable. This review highlights the basic biology of cynobacterial hydrogen production, strains involved, large-scale hydrogen production and its future prospects. While integrating the existing knowledge and technology, much future improvement and progress is to be done before hydrogen is accepted as a commercial primary energy source. PMID:16371161

  15. Production of shikimic acid.

    PubMed

    Ghosh, Saptarshi; Chisti, Yusuf; Banerjee, Uttam C

    2012-01-01

    Shikimic acid is a key intermediate for the synthesis of the antiviral drug oseltamivir (Tamiflu®). Shikimic acid can be produced via chemical synthesis, microbial fermentation and extraction from certain plants. An alternative production route is via biotransformation of the more readily available quinic acid. Much of the current supply of shikimic acid is sourced from the seeds of Chinese star anise (Illicium verum). Supply from star anise seeds has experienced difficulties and is susceptible to vagaries of weather. Star anise tree takes around six-years from planting to bear fruit, but remains productive for long. Extraction and purification from seeds are expensive. Production via fermentation is increasing. Other production methods are too expensive, or insufficiently developed. In the future, production in recombinant microorganisms via fermentation may become established as the preferred route. Methods for producing shikimic acid are reviewed.

  16. Product definition data interface

    NASA Technical Reports Server (NTRS)

    Birchfield, B.; Downey, P.

    1984-01-01

    The development and application of advanced Computer Aided Design/Computer Aided Manufacturing (CAD/CAM) technology in aerospace industry is discussed. New CAD/CAM capabilities provide the engineer and production worker with tools to produce better products and significantly improve productivity. This technology is expanding in all phases of engineering and manufacturing with large potential for improvements in productivity. The integration of CAD and CAM systematically to insure maximum utility throughout the U.S. Aerospace Industry, its large community of supporting suppliers, and the Department of Defense aircraft overhaul and repair facilities is outlined. The need for a framework for exchange of digital product definition data, which serves the function of the conventional engineering drawing is emphasized.

  17. Sunscreen product formulation.

    PubMed

    Tanner, Paul R

    2006-01-01

    On the surface, sunscreen products are pretty simple. They consist of a delivery vehicle containing one or more sunscreen active ingredients. When applied to the skin, these sunscreen actives intercept solar ultraviolet (UV) rays before they can damage the underlying skin. However, while conceptually simple, a detailed analysis reveals that sunscreen formulations are quite complex, requiring careful selection of sunscreen active and vehicle components to control multiple performance and in-use parameters.Thus, to enable a better understanding and appreciation of sunscreen products, the typical steps in formulating a sunscreen product are described. Throughout this process, the key is to apply scientific principles together with a bit of formulation art to holistically create the best sunscreen product that meets the design targets--a sunscreen product that people will use regularly and properly.

  18. Thorium in mineral products.

    PubMed

    Collier, D E; Brown, S A; Blagojevic, N; Soldenhoff, K H; Ring, R J

    2001-01-01

    Many ores contain low levels of thorium. When these ores are processed, the associated radioactivity can be found in mineral concentrates, intermediates and final products. There is an incentive for industries to remove radioactivity from mineral products to allow the movement and sale of these materials, both nationally and internationally, without the need for licensing. Control of thorium in various products involves the development and optimisation of process steps to be able to meet product specifications. The Australian Nuclear Science and Technology Organisation (ANSTO) has undertaken a range of R & D programmes targeting the treatment of thorium-bearing minerals. This paper discusses the application of a microprobe technique for siting radioactivity in zircon and ilmenite and the problems experienced in measuring the concentrations in solid rare earth products.

  19. Firewall products today

    SciTech Connect

    Cooper, S.P.

    1995-02-01

    With an increased interest in connecting to the Internet, there is a corresponding interest in protecting an organization`s network from others on the Internet. Internet firewalls help protect an organization`s network, and the increased demand for firewalls have brought about a number of freeware and commercial products. But how does someone determine the best product or service for their organization? This paper discusses things that need to be considered in deciding to build or purchase a firewall system. It discusses many of the products, features, and services that are commercially available and what components they include such as software, hardware, consulting, or a combination thereof. This paper is not an attempt to evaluate the products. The aim is to provide an awareness of what is currently available and their capabilities. An appendix gives contact information for all of the vendors whose product information was used in developing this paper.

  20. Product definition data interface

    NASA Technical Reports Server (NTRS)

    Birchfield, B.; Downey, P.

    1984-01-01

    The development and application of advanced Computer Aided Design/Computer Aided Manufacturing (CAD/CAM) technology in aerospace industry is discussed. New CAD/CAM capabilities provide the engineer and production worker with tools to produce better products and significantly improve productivity. This technology is expanding in all phases of engineering and manufacturing with large potential for improvements in productivity. The integration of CAD and CAM systematically to insure maximum utility throughout the U.S. Aerospace Industry, its large community of supporting suppliers, and the Department of Defense aircraft overhaul and repair facilities is outlined. The need for a framework for exchange of digital product definition data, which serves the function of the conventional engineering drawing is emphasized.

  1. SMAP Science Data Products

    NASA Astrophysics Data System (ADS)

    Cuddy, D.

    2014-12-01

    NASA's Soil Moisture Active Passive (SMAP) mission will retrieve global surface soil moisture and freeze/thaw state based on measurements acquired by remote sensing instruments that fly on an Earth orbiting satellite. The SMAP observatory will launch no earlier than January 8, 2015 into a near-polar, sun-synchronous orbit. The SMAP instrument suite includes a radiometer and synthetic aperture radar. This paper will describe the Science Data System (SDS) that will process the SMAP raw data into higher-level products. SMAP data products will provide calibrated radar backscatter and radiometer brightness temperatures, derived geophysical parameters in the form of soil moisture and freeze/thaw states, daily maps of these geophysical parameters, as well as modeled analyses of global soil moisture and carbon flux in Boreal regions. The SDS is a fully automated system that will process the incoming raw data from the instruments, incorporate spacecraft and instrument engineering data, and use both dynamic and static ancillary products from the scientific community. The SDS will produce 14 standard data product processors. This paper will discuss the standard data products, their format, metadata, quality assessment products, as well as the planned release dates for the products both Beta and Validated quality. The standard data products will appear in Hierarchical Data Format-5 (HDF5) format. The products will contain metadata that conform to the ISO 19115 standard. The Alaska Satellite Facility (ASF) will host and distribute SMAP Radar data, while the National Snow and Ice Data Center (NSIDC) will host and distribute all other SMAP products.

  2. History of glutamate production.

    PubMed

    Sano, Chiaki

    2009-09-01

    In 1907 Kikunae Ikeda, a professor at the Tokyo Imperial University, began his research to identify the umami component in kelp. Within a year, he had succeeded in isolating, purifying, and identifying the principal component of umami and quickly obtained a production patent. In 1909 Saburosuke Suzuki, an entrepreneur, and Ikeda began the industrial production of monosodium l-glutamate (MSG). The first industrial production process was an extraction method in which vegetable proteins were treated with hydrochloric acid to disrupt peptide bonds. l-Glutamic acid hydrochloride was then isolated from this material and purified as MSG. Initial production of MSG was limited because of the technical drawbacks of this method. Better methods did not emerge until the 1950s. One of these was direct chemical synthesis, which was used from 1962 to 1973. In this procedure, acrylonitrile was the starting material, and optical resolution of dl-glutamic acid was achieved by preferential crystallization. In 1956 a direct fermentation method to produce glutamate was introduced. The advantages of the fermentation method (eg, reduction of production costs and environmental load) were large enough to cause all glutamate manufacturers to shift to fermentation. Today, total world production of MSG by fermentation is estimated to be 2 million tons/y (2 billion kg/y). However, future production growth will likely require further innovation.

  3. IRIS Product Recommendations

    NASA Technical Reports Server (NTRS)

    Short, David A.

    2000-01-01

    This report presents the Applied Meteorology Unit's (AMU) evaluation of SIGMET Inc.'s Integrated Radar Information System (IRIS) Product Generator and recommendations for products emphasizing lightning and microburst tools. The IRIS Product Generator processes radar reflectivity data from the Weather Surveillance Radar, model 74C (WSR-74C), located on Patrick Air Force Base. The IRIS System was upgraded from version 6.12 to version 7.05 in late December 1999. A statistical analysis of atmospheric temperature variability over the Cape Canaveral Air Force Station (CCAFS) Weather Station provided guidance for the configuration of radar products that provide information on the mixed-phase (liquid and ice) region of clouds, between 0 C and -20 C. Mixed-phase processes at these temperatures are physically linked to electrification and the genesis of severe weather within convectively generated clouds. Day-to-day variations in the atmospheric temperature profile are of sufficient magnitude to warrant periodic reconfiguration of radar products intended for the interpretation of lightning and microburst potential of convectively generated clouds. The AMU also examined the radar volume-scan strategy to determine the scales of vertical gaps within the altitude range of the 0 C to -20 C isotherms over the Kennedy Space Center (KSC)/CCAFS area. This report present's two objective strategies for designing volume scans and proposes a modified scan strategy that reduces the average vertical gap by 37% as a means for improving radar observations of cloud characteristics in the critical 0 C to -20 C layer. The AMU recommends a total of 18 products, including 11 products that require use of the IRIS programming language and the IRIS User Product Insert feature. Included is a cell trends product and display, modeled after the WSR-88D cell trends display in use by the National Weather Service.

  4. Cyanobacterial chemical production.

    PubMed

    Case, Anna E; Atsumi, Shota

    2016-08-10

    The increase in global temperatures caused by rising CO2 levels necessitates the development of alternative sources of fuel and chemicals. One appealing alternative that has been receiving increased attention in recent years is the photosynthetic conversion of atmospheric CO2 to biofuels and chemical products using genetically engineered cyanobacteria. This can help to not only provide an alternate "greener" source for some of the most popular petroleum based products but it can also help to reduce atmospheric CO2. Utilizing cyanobacteria rather than plants allows for reduced land requirements and reduces competition with food crops. This review discusses advancements in the field since 2012 with a particular emphasis on production of hydrocarbons.

  5. Fundamentals of energy production

    NASA Astrophysics Data System (ADS)

    Harder, E. L.

    The theory, methods of conversion, and costs of various energy sources, transformations, and production techniques are summarized. Specific attention is given to carbon-based fuels in liquid, gaseous, and solid forms and processes for producing synthetic fuels. Additional details are presented for hydrogen and biomass technologies, as well as nuclear fuel-based electricity production. Renewable energy methods are dealt with in terms of the potentials and current applications of tidal generating stations, hydroelectric installations, solar thermal and electrical energy production, and the development of large wind turbines. Consideration is given to the environmental effects of individual energy technologies, along with associated costs and transportability of the energy produced.

  6. Versioning of printed products

    NASA Astrophysics Data System (ADS)

    Tuijn, Chris

    2004-12-01

    During the definition of a printed product in an MIS system, a lot of attention is paid to the production process. The MIS systems typically gather all process-related parameters at such a level of detail that they can determine what the exact cost will be to make a specific product. This information can then be used to make a quote for the customer. Considerably less attention is paid to the content of the products since this does not have an immediate impact on the production costs (assuming that the number of inks or plates is known in advance). The content management is typically carried out either by the prepress systems themselves or by dedicated workflow servers uniting all people that contribute to the manufacturing of a printed product. Special care must be taken when considering versioned products. With versioned products we here mean distinct products that have a number of pages or page layers in common. Typical examples are comic books that have to be printed in different languages. In this case, the color plates can be shared over the different versions and the black plate will be different. Other examples are nation-wide magazines or newspapers that have an area with regional pages or advertising leaflets in different languages or currencies. When considering versioned products, the content will become an important cost factor. First of all, the content management (and associated proofing and approval cycles) becomes much more complex and, therefore, the risk that mistakes will be made increases considerably. Secondly, the real production costs are very much content-dependent because the content will determine whether plates can be shared across different versions or not and how many press runs will be needed. In this paper, we will present a way to manage different versions of a printed product. First, we will introduce a data model for version management. Next, we will show how the content of the different versions can be supplied by the customer

  7. Versioning of printed products

    NASA Astrophysics Data System (ADS)

    Tuijn, Chris

    2005-01-01

    During the definition of a printed product in an MIS system, a lot of attention is paid to the production process. The MIS systems typically gather all process-related parameters at such a level of detail that they can determine what the exact cost will be to make a specific product. This information can then be used to make a quote for the customer. Considerably less attention is paid to the content of the products since this does not have an immediate impact on the production costs (assuming that the number of inks or plates is known in advance). The content management is typically carried out either by the prepress systems themselves or by dedicated workflow servers uniting all people that contribute to the manufacturing of a printed product. Special care must be taken when considering versioned products. With versioned products we here mean distinct products that have a number of pages or page layers in common. Typical examples are comic books that have to be printed in different languages. In this case, the color plates can be shared over the different versions and the black plate will be different. Other examples are nation-wide magazines or newspapers that have an area with regional pages or advertising leaflets in different languages or currencies. When considering versioned products, the content will become an important cost factor. First of all, the content management (and associated proofing and approval cycles) becomes much more complex and, therefore, the risk that mistakes will be made increases considerably. Secondly, the real production costs are very much content-dependent because the content will determine whether plates can be shared across different versions or not and how many press runs will be needed. In this paper, we will present a way to manage different versions of a printed product. First, we will introduce a data model for version management. Next, we will show how the content of the different versions can be supplied by the customer

  8. Silicon production process evaluations

    NASA Technical Reports Server (NTRS)

    1982-01-01

    Chemical engineering analyses involving the preliminary process design of a plant (1,000 metric tons/year capacity) to produce silicon via the technology under consideration were accomplished. Major activities in the chemical engineering analyses included base case conditions, reaction chemistry, process flowsheet, material balance, energy balance, property data, equipment design, major equipment list, production labor and forward for economic analysis. The process design package provided detailed data for raw materials, utilities, major process equipment and production labor requirements necessary for polysilicon production in each process.

  9. Gasohol: outlook for production

    SciTech Connect

    Jenkins, D.M.

    1981-11-01

    The US Department of Energy has set goals for alcohol production of 920 million gallons per year by the end of 1982 and 1.8 billion gallons per year by the end of 1985, to provide an alternative source of energy. The production of ethanol from sugar crops, grains and tubers, and other crops is reviewed. The recovery of fuel-grade alcohol from fermentation beers, and the energy requirements to make anhydrous alcohol are discussed. The economics of alcohol production and the financial incentives offered by the United States Government are summarized.

  10. Small satellite product assurance

    NASA Astrophysics Data System (ADS)

    Demontlivault, J.; Cadelec, Jacques

    1993-01-01

    In order to increase the interest in small satellites, their cost must be reduced; reducing product assurance costs induced by quality requirements is a major objective. For a logical approach, small satellites are classified in three main categories: satellites for experimental operations with a short lifetime, operational satellites manufactured in small mass with long lifetime requirements, operational satellites (long lifetime required), of which only a few models are produced. The various requirements as regards the product assurance are examined for each satellite category: general requirements for space approach, reliability, electronic components, materials and processes, quality assurance, documentation, tests, and management. Ideal product assurance system integrates quality teams and engineering teams.

  11. Product engineering and sustainability

    NASA Astrophysics Data System (ADS)

    Janssen, L. P. B. M.; Janssen, C. H. C.

    2016-11-01

    Chemical engineering has made a substantial contribution to the improvement of the environment during the last decades. Many processes have become more sustainable and harmful waste streams are minimised. However, considerable improvement of sustainability can still be obtained in product engineering and design. Especially the aspects that are important at the end of the life cycle of the product can be improved considerably. A priority list for the design of more sustainable products is presented and illustrated with examples of daily chemical engineering practice.

  12. Biomass production in Florida

    SciTech Connect

    Smith, W.H.; Dowd, M.L.

    1981-08-01

    Florida posseses climatic, land, and water resources favorable for abundant biomass production. Therefore, a statewide program has been initiated to determine adapted species for the available array of production sites. Plant resources under investigation include woody, aquatic, grasses, hydrocarbon, and root crop species. The goal is to produce a continuous stream of biomass for the various biofuel conversion options. Preliminary yields from energy cropping experiments range from about 10 to nearly 90 metric tons per hectare per year, depending on the crop and the production systems employed. (Refs. 15).

  13. 17 CFR 229.1204 - (Item 1204) Oil and gas production, production prices and production costs.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... conversion to synthetic oil or gas, the product's production, transfer prices, and production costs should be... 17 Commodity and Securities Exchanges 2 2011-04-01 2011-04-01 false (Item 1204) Oil and gas production, production prices and production costs. 229.1204 Section 229.1204 Commodity and Securities...

  14. Food Production Info Sharing

    NASA Image and Video Library

    2017-07-12

    Bryan Onate, Advanced Plant Habitat project manager, with the Exploration Research and Technology Directorate, brainstorms innovative approaches to food production with industry representatives inside a laboratory at the Space Station Processing Facility at NASA's Kennedy Space Center in Florida.

  15. Food Production Info Sharing

    NASA Image and Video Library

    2017-07-13

    Scientists in the Exploration Research and Technology Directorate brainstorm innovative approaches to food production with industry representatives at the Space Station Processing Facility at NASA's Kennedy Space Center in Florida.

  16. JWST science data products

    NASA Astrophysics Data System (ADS)

    Swade, Daryl; Bushouse, Howard; Greene, Gretchen; Swam, Michael

    2014-07-01

    Science data products for James Webb Space Telescope (JWST) ©observations will be generated by the Data Management Subsystem (DMS) within the JWST Science and Operations Center (S&OC) at the Space Telescope Science Institute (STScI). Data processing pipelines within the DMS will produce uncalibrated and calibrated exposure files, as well as higher level data products that result from combined exposures, such as mosaic images. Information to support the science observations, for example data from engineering telemetry, proposer inputs, and observation planning will be captured and incorporated into the science data products. All files will be generated in Flexible Image Transport System (FITS) format. The data products will be made available through the Mikulski Archive for Space Telescopes (MAST) and adhere to International Virtual Observatory Alliance (IVOA) standard data protocols.

  17. New CALIPSO Data Products

    Atmospheric Science Data Center

    2013-07-10

    ... they are received at the ground station. They use the most current attitude information and a calibration and analysis scheme. Each ... quality standard data products will be available. Science investigations to be published in research journals should, therefore, not be ...

  18. Increasing Public Library Productivity.

    ERIC Educational Resources Information Center

    Samuelson, Howard

    1981-01-01

    Suggests ways of improving productivity for public libraries faced with increased accountability, dwindling revenues, and continuing inflation. Techniques described include work simplification, work analysis, improved management, and employee motivation. (RAA)

  19. CALIPSO Data Products Catalog

    Atmospheric Science Data Center

    2013-11-12

    ... Computed_Brightness_Temperature_Surface, Multi_Layer_Cloud_Flag, and Microphysics Removed the following parameters ... and cloud profile data products. The 532 nm and 1064 nm ozone absorption cross-sections were updated and added to the metadata records ...

  20. Hydrocodone Combination Products

    MedlinePlus

    ... Other hydrocodone combination products are used to relieve cough. Hydrocodone is in a class of medications called ... and nervous system respond to pain. Hydrocodone relieves cough by decreasing activity in the part of the ...

  1. Equipment & New Products

    ERIC Educational Resources Information Center

    Poitras, Adrian W., Ed.

    1976-01-01

    Listed are a number of materials including a spectrophotometer, power meter, vacuum pump, fume hood, cart system, and others. The source of the product and a brief description are given for each. (RH)

  2. Nonessential Products Ban Program

    EPA Pesticide Factsheets

    Learn about EPA's efforts to address ozone layer depletion by banning the sale and introduction into interstate commerce of certain non-essential products manufactured with or containing ozone-depleting substances.

  3. Phonemes and Production.

    PubMed

    Dell, Gary S

    2014-01-01

    This comment offers observations that support Hickok's claim that phoneme sized representations are involved more in speech production than speech perception, but notes that languages may vary with regard to the importance of the phoneme.

  4. Lipid Production from Nannochloropsis

    PubMed Central

    Ma, Xiao-Nian; Chen, Tian-Peng; Yang, Bo; Liu, Jin; Chen, Feng

    2016-01-01

    Microalgae are sunlight-driven green cell factories for the production of potential bioactive products and biofuels. Nannochloropsis represents a genus of marine microalgae with high photosynthetic efficiency and can convert carbon dioxide to storage lipids mainly in the form of triacylglycerols and to the ω-3 long-chain polyunsaturated fatty acid eicosapentaenoic acid (EPA). Recently, Nannochloropsis has received ever-increasing interests of both research and public communities. This review aims to provide an overview of biology and biotechnological potential of Nannochloropsis, with the emphasis on lipid production. The path forward for the further exploration of Nannochloropsis for lipid production with respect to both challenges and opportunities is also discussed. PMID:27023568

  5. Southern pulpwood production, 1961

    Treesearch

    Vernon L. Robinson; Agnes C. Nichols

    1962-01-01

    Southern pulpwood production reached 24,230,728 cords in 1961--60 percent of the Nations total. Significant increases were noted in the consumption of hardwood and residues. But pine roundwood remained virtually unchanged for the third consecutive year.

  6. Herbal Products and Supplements

    MedlinePlus

    ... 2005familydoctor.org editorial staffOver-the-counter ProductsDrug-Nutrient Interactions and Drug-Supplement Interactions | Drug Interactions with St. John's WortOctober 2016October 2016familydoctor. ...

  7. CALIPSO Expedited Products

    Atmospheric Science Data Center

    2013-07-10

    ... Thursday, January 31, 2013 The Atmospheric Science Data Center (ASDC) at NASA Langley Research Center in collaboration ... Science investigations to be published in research journals should, therefore, not be based on the Expedited data products, but ...

  8. Phonemes and Production

    PubMed Central

    Dell, Gary S.

    2013-01-01

    This comment offers observations that support Hickok’s claim that phoneme sized representations are involved more in speech production than speech perception, but notes that languages may vary with regard to the importance of the phoneme. PMID:24443620

  9. CERES FSW Data Products

    Atmospheric Science Data Center

    2014-07-24

    CERES FSW Data Products Level 3:  Spatially (1°x1° lat/lon ... Description : Monthly Gridded Radiative Fluxes and Clouds (FSW): Regional averages of instantaneous footprint computed fluxes [TOA, ...

  10. Colloidal Silver Products

    MedlinePlus

    ... can be dangerous to your health. What the Science Says About the Safety and Side Effects of ... homemade and commercial colloidal silver products. What the Science Says About the Effectiveness of Colloidal Silver Scientific ...

  11. Land Product Validation (LPV)

    NASA Technical Reports Server (NTRS)

    Schaepman, Gabriela; Roman, Miguel O.

    2013-01-01

    This presentation will discuss Land Product Validation (LPV) objectives and goals, LPV structure update, interactions with other initiatives during report period, outreach to the science community, future meetings and next steps.

  12. Production of solvated electrons

    NASA Technical Reports Server (NTRS)

    Thomas, J. K.

    1969-01-01

    Current research, both theoretical and experimental, relating to the production and kinetics of interactions of solvated electrons is reviewed. Particular attention is focused on solvated electrons generated by ionizing radiation in water, alcohols, and organic systems.

  13. Cancer immunotherapy products

    PubMed Central

    Camarero, Jorge; Ruiz, Sol

    2012-01-01

    Active immunotherapy products (widely known as “cancer vaccines”) are products intended to stimulate an immune response to mediate tumor destruction or reduce the progression of disease in patients where cancer has been diagnosed. Some quality attributes of these products are very difficult to characterize or present a high variability (especially if they are for autologous use), further complicating the interpretation of some of the clinical data. Furthermore, questions arise in the evaluation of efficacy and safety data in comparison with current chemical or biological treatments for the same indications. Some of these aspects are discussed in this paper in relationship with the regulatory requirements in the European Union and as applied to two recently assessed medicinal products, Oncophage and Provenge, both considered therapeutic “cancer vaccines” for renal cell carcinoma and prostate cancer, respectively. PMID:22863755

  14. Cyanobacterial biofuel production.

    PubMed

    Machado, Iara M P; Atsumi, Shota

    2012-11-30

    The development of new technologies for production of alternative fuel became necessary to circumvent finite petroleum resources, associate rising costs, and environmental concerns due to rising fossil fuel CO₂ emissions. Several alternatives have been proposed to develop a sustainable industrial society and reduce greenhouse emissions. The idea of biological conversion of CO₂ to fuel and chemicals is receiving increased attention. In particular, the direct conversion of CO₂ with solar energy to biofuel by photosynthetic microorganisms such as microalgae and cyanobacteria has several advantages compared to traditional biofuel production from plant biomass. Photosynthetic microorganisms have higher growth rates compared with plants, and the production systems can be based on non-arable land. The advancement of synthetic biology and genetic manipulation has permitted engineering of cyanobacteria to produce non-natural chemicals typically not produced by these organisms in nature. This review addresses recent publications that utilize different approaches involving engineering cyanobacteria for production of high value chemicals including biofuels.

  15. Atmospheric Chemistry Data Products

    NASA Technical Reports Server (NTRS)

    2003-01-01

    This presentation poster covers data products from the Distributed Active Archive Center (DAAC) of the Goddard Earth Sciences (GES) Data and Information Services Center (DISC). Total Ozone Mapping Spectrometer products (TOMS) introduced in the presentation include TOMS Version 8 as well as Aura, which provides 25 years of TOMS and Upper Atmosphere Research Satellite (UARS) data. The presentation lists a number of atmospheric chemistry and dynamics data sets at DAAC.

  16. Quadrigia and Productivity.

    PubMed

    Ingraham, John

    2017-07-01

    Financial productivity in academic surgery is important and deserves great emphasis, yet it is but one of many vital elements of a healthy practice. Productivity must be carefully balanced with many other vital goals such as maximizing patient safety, maintaining excellent outcomes, optimizing resident and medical student education, and earning outstanding patient feedback. The following editorial explores this elusive balance and the importance of not swaying too far in the direction of revenue.

  17. Food Product Dating

    MedlinePlus

    ... Administrative Forms Standard Forms Skip Navigation Z7_0Q0619C0JGR010IFST1G5B10H1 Web Content Viewer (JSR 286) Actions ${title} Loading... / Topics / ... Food Product Dating / Food Product Dating Z7_0Q0619C0JGR010IFST1G5B10H3 Web Content Viewer (JSR 286) Actions ${title} Loading... Z7_ ...

  18. Purchasing Productivity Measurement Systems.

    DTIC Science & Technology

    1980-09-01

    Defense More Productive", Perspectives in Defense Management, Winter 1974-1975. 4. Encyclopaedia Britannica, Macropaedia, " Taylor , Frederick Winslow ", v...Some of the earliest successes in Productivity Systems and studies are attributed to Frederick W. Taylor and his concept of Scientific Management...sociological interactions. Taylorism , as it became known, provoked resentment and opposition from labor when it was carried to extremes. It was, however

  19. Southern pulpwood production, 1967

    Treesearch

    Noel D. Cost

    1967-01-01

    Pulpwood production in the south leveled off slightly in 1968 but still established another record high of 33,651,100 cords—63 percent of the Nation’s total. Significant gains were noted in the use of residues, whereas roundwood production showed a light decrease for the first time in 10 years. At the year’s end, there were 92 mills in the operation of the South with a...

  20. Magnetite and its production

    SciTech Connect

    Koebbe, E.R.

    1993-12-31

    The supply of high quality magnetite for the cleaning of coal using dense medium cyclones and vessels is of concern to all coal preparation operations. This paper describes the production of high purity magnetite (Fe{sub 3}O{sub 4}) from a domestic underground mining operation in Missouri, Pea Ridge Iron Ore Company. Emphasis will be placed on the mining and processing of the magnetite ore into the various magnetite products required by coal preparation plants.

  1. PRODUCTION OF TRITIUM

    DOEpatents

    Jenks, G.H.; Shapiro, E.M.; Elliott, N.; Cannon, C.V.

    1963-02-26

    This invention relates to a process for the production of tritium by subjecting comminuted solid lithium fluoride containing the lithium isotope of atomic mass number 6 to neutron radiation in a self-sustaining neutronic reactor. The lithium fiuoride is heated to above 450 deg C. in an evacuated vacuum-tight container during radiation. Gaseous radiation products are withdrawn and passed through a palladium barrier to recover tritium. (AEC)

  2. Southern pulpwood production, 1966

    Treesearch

    Dwane D. Van Hooser; Joe F. Christopher

    1967-01-01

    Pulpwood production in the South rose 7 percent in 1966, to 33,061,243 cords. This is the highest output on record and the ninth consecutive increase in annual production. Pine round-wood accounted for 57 percent of the increase, and residues or byproducts from other wood-using industries, 26 percent. The remainder was due to an increase in the harvest of hard-wood...

  3. Military Production Urgencies System

    DTIC Science & Technology

    1955-08-17

    echelons. I4. To guide preparation of specific urgency lists for the time -phased demands of supporting industrial resources. 5. To indicate the...AD-A270 736 ELECTE aeprlnt Incorporating Transmittal 61-2 Au-uast 17, 1955 Department of Defense Directive SUBJECT Military Production Urgencies ...Departaent of Defense Military Production Urgencies System which will provide authoritative information for guidance as to the relative urgency of desired

  4. Ethanol production from lignocellulose

    DOEpatents

    Ingram, Lonnie O.; Wood, Brent E.

    2001-01-01

    This invention presents a method of improving enzymatic degradation of lignocellulose, as in the production of ethanol from lignocellulosic material, through the use of ultrasonic treatment. The invention shows that ultrasonic treatment reduces cellulase requirements by 1/3 to 1/2. With the cost of enzymes being a major problem in the cost-effective production of ethanol from lignocellulosic material, this invention presents a significant improvement over presently available methods.

  5. Charmonia Production at Lhcb

    NASA Astrophysics Data System (ADS)

    Artamonov, Alexander

    2013-12-01

    In this article we present a short review on measurements of charmonia production at the LHCb experiment carried out during 2010, 2011 and 2012 data taking periods. The review covers the production of J/ψ, ψ(2S), χc, J/ψJ/ψ, as well as J/ψ in association with open charm. We also review the measurement of J/ψ polarization. The results are compared to theoretical predictions.

  6. Pretreated densified biomass products

    DOEpatents

    Dale, Bruce E; Ritchie, Bryan; Marshall, Derek

    2014-03-18

    A product comprising at least one densified biomass particulate of a given mass having no added binder and comprised of a plurality of lignin-coated plant biomass fibers is provided, wherein the at least one densified biomass particulate has an intrinsic density substantially equivalent to a binder-containing densified biomass particulate of the same given mass and h a substantially smooth, non-flakey outer surface. Methods for using and making the product are also described.

  7. 1964 Oregon log production.

    Treesearch

    Brian R. Wall

    1965-01-01

    The production of logs in Oregon in 1964 was 9.4 billion board feet, or nearly 9 percent above 1963. This year, 1964, had the third highest level of log production in history, exceeded only in 1955 and in 1952. The proportion of total cut from private lands fell to 43 percent, even though the total private cut increased 6 percent over that in 1963. Forest industry,...

  8. Material and energy productivity.

    PubMed

    Steinberger, Julia K; Krausmann, Fridolin

    2011-02-15

    Resource productivity, measured as GDP output per resource input, is a widespread sustainability indicator combining economic and environmental information. Resource productivity is ubiquitous, from the IPAT identity to the analysis of dematerialization trends and policy goals. High resource productivity is interpreted as the sign of a resource-efficient, and hence more sustainable, economy. Its inverse, resource intensity (resource per GDP) has the reverse behavior, with higher values indicating environmentally inefficient economies. In this study, we investigate the global systematic relationship between material, energy and carbon productivities, and economic activity. We demonstrate that different types of materials and energy exhibit fundamentally different behaviors, depending on their international income elasticities of consumption. Biomass is completely inelastic, whereas fossil fuels tend to scale proportionally with income. Total materials or energy, as aggregates, have intermediate behavior, depending on the share of fossil fuels and other elastic resources. We show that a small inelastic share is sufficient for the total resource productivity to be significantly correlated with income. Our analysis calls into question the interpretation of resource productivity as a sustainability indicator. We conclude with suggestions for potential alternatives.

  9. Belle II production system

    NASA Astrophysics Data System (ADS)

    Miyake, Hideki; Grzymkowski, Rafal; Ludacka, Radek; Schram, Malachi

    2015-12-01

    The Belle II experiment will record a similar quantity of data to LHC experiments and will acquire it at similar rates. This requires considerable computing, storage and network resources to handle not only data created by the experiment but also considerable amounts of simulated data. Consequently Belle II employs a distributed computing system to provide the resources coordinated by the the DIRAC interware. DIRAC is a general software framework that provides a unified interface among heterogeneous computing resources. In addition to the well proven DIRAC software stack, Belle II is developing its own extension called BelleDIRAC. BelleDIRAC provides a transparent user experience for the Belle II analysis framework (basf2) on various environments and gives access to file information managed by LFC and AMGA metadata catalog. By unifying DIRAC and BelleDIRAC functionalities, Belle II plans to operate an automated mass data processing framework named a “production system”. The Belle II production system enables large-scale raw data transfer from experimental site to raw data centers, followed by massive data processing, and smart data delivery to each remote site. The production system is also utilized for simulated data production and data analysis. Although development of the production system is still on-going, recently Belle II has prepared prototype version and evaluated it with a large scale simulated data production. In this presentation we will report the evaluation of the prototype system and future development plans.

  10. CYTOTOXIC PHOSPHOLIPID OXIDATION PRODUCTS

    PubMed Central

    Chen, Rui; Yang, Lili; McIntyre, Thomas M.

    2008-01-01

    Phospholipid oxidation products accumulate in the necrotic core of atherosclerotic lesions, in apoptotic cells, and circulate in oxidized LDL. Phospholipid oxidation generates toxic products, but little is known about which specific products are cytotoxic, their receptors, or the mechanism(s) that induces cell death. We find the most common phospholipid oxidation product of oxidized LDL, phosphatidylcholine with esterified sn-2 azelaic acid, induced apoptosis at low micromolar concentrations. The synthetic ether phospholipid hexadecyl azelaoyl phosphatidylcholine (HAzPC) was rapidly internalized, and over-expression of PLA2g7 (PAF acetylhydrolase) that specifically hydrolyzes such oxidized phospholipids suppressed apoptosis. Internalized HAzPC associated with mitochondria, and cytochrome C and apoptosis-inducing factor escaped from mitochondria to the cytoplasm and nucleus, respectively, in cells exposed to HAzPC. Isolated mitochondria exposed to HAzPC rapidly swelled, and released cytochrome C and apoptosis-inducing factor. Other phospholipid oxidation products induced swelling, but HAzPC was the most effective and was twice as effective as its diacyl homolog. Cytoplasmic cytochrome C completes the apoptosome, and activated caspase 9 and 3 were present in cells exposed to HAzPC. Irreversible inhibition of caspase 9 blocked downstream caspase 3 activation, and prevented apoptosis. Mitochondrial damage initiated this apoptotic cascade because over-expression of Bcl-XL, an anti-apoptotic protein localized to mitochondria, blocked cytochrome C escape, and apoptosis. Thus, exogenous phospholipid oxidation products target intracellular mitochondria to activate the intrinsic apoptotic cascade. PMID:17597068

  11. Material and Energy Productivity

    PubMed Central

    2011-01-01

    Resource productivity, measured as GDP output per resource input, is a widespread sustainability indicator combining economic and environmental information. Resource productivity is ubiquitous, from the IPAT identity to the analysis of dematerialization trends and policy goals. High resource productivity is interpreted as the sign of a resource-efficient, and hence more sustainable, economy. Its inverse, resource intensity (resource per GDP) has the reverse behavior, with higher values indicating environmentally inefficient economies. In this study, we investigate the global systematic relationship between material, energy and carbon productivities, and economic activity. We demonstrate that different types of materials and energy exhibit fundamentally different behaviors, depending on their international income elasticities of consumption. Biomass is completely inelastic, whereas fossil fuels tend to scale proportionally with income. Total materials or energy, as aggregates, have intermediate behavior, depending on the share of fossil fuels and other elastic resources. We show that a small inelastic share is sufficient for the total resource productivity to be significantly correlated with income. Our analysis calls into question the interpretation of resource productivity as a sustainability indicator. We conclude with suggestions for potential alternatives. PMID:21210661

  12. Microbial production of propanol.

    PubMed

    Walther, Thomas; François, Jean Marie

    2016-01-01

    Both, n-propanol and isopropanol are industrially attractive value-added molecules that can be produced by microbes from renewable resources. The development of cost-effective fermentation processes may allow using these alcohols as a biofuel component, or as a precursor for the chemical synthesis of propylene. This review reports and discusses the recent progress which has been made in the biochemical production of propanol. Several synthetic propanol-producing pathways were developed that vary with respect to stoichiometry and metabolic entry point. These pathways were expressed in different host organisms and enabled propanol production from various renewable feedstocks. Furthermore, it was shown that the optimization of fermentation conditions greatly improved process performance, in particular, when continuous product removal prevented accumulation of toxic propanol levels. Although these advanced metabolic engineering and fermentation strategies have facilitated significant progress in the biochemical production of propanol, the currently achieved propanol yields and productivities appear to be insufficient to compete with chemical propanol synthesis. The development of biosynthetic pathways with improved propanol yields, the breeding or identification of microorganisms with higher propanol tolerance, and the engineering of propanol producer strains that efficiently utilize low-cost feedstocks are the major challenges on the way to industrially relevant microbial propanol production processes.

  13. GSICS Satellite Intercalibration Products

    NASA Astrophysics Data System (ADS)

    Bali, M.; Flynn, L. E.

    2015-12-01

    Monitoring satellite instrument measurements (Top of Atmosphere radiances) while they are orbiting by comparing them with in-orbit stable references has emerged as a key component of ensuring quality (the stability and accuracy) of their measurements and correcting any biases that emerge during the mission. In 2006 the World Meteorological Organization (WMO) and the CGMS together initiated the Gobal Space Based Inter-Calibration System (GSICS,gsics.wmo.int) with the aim of monitoring the quality of measurement from satellite instruments launched by member including NASA, NOAA, EUMETSAT, ISRO CMA KMA CNES. In recent years, GSICS, via collaboration among member agencies across nations has successfully monitored instrument records for both GEO (GOES, SEVIRI, MTSAT) and LEO (AVHRR) based instruments by comparing them to in-orbit references such as IASI, AIRS and MODIS. The cross comparison products undergo stringent quality checks and standarizations and a scientific review of the theoretical bases and are assigned a GSICS maturity level. The accepted products are distributed freely as GSICS correction products. These products have wide applications. The goal of the presentation is to introduce GSICS cross calibration products and demonstrate their applications in developing products such as Fundamental Climate Data Records (FCDRs), evaluating Spectral Response Function status, and providing bias corrections. The impact of the GSICS bias corrections on retrieval of downstream variables such as Cloud Height Sea Surface Temperature will be one component of the presentation.

  14. Whither tobacco product regulation?

    PubMed

    McNeill, Ann; Hammond, David; Gartner, Coral

    2012-03-01

    Despite decades of industry innovation and regulatory efforts, the harmfulness of conventional cigarettes has not changed. There are several pitfalls in this area, including the long time lag before health impacts of product regulatory changes become apparent, the danger of consumers deriving false reassurance of lesser harm in the interim period, the lack of relevant expertise and the lack of an internationally agreed and evidence-based strategic approach. Articles 9 and 10 of the Framework Convention on Tobacco Control provide the potential for such a global strategy, and knowledge and research has increased significantly over recent years. However, there are huge opportunity costs in implementing product disclosure and regulatory strategies: most national regulators have very limited human and financial resources, which should be focused on other evidence-based tobacco control interventions. We believe therefore that it is now time to abandon the notion of safe or safer cigarettes while moving consumers towards cleaner nicotine products as soon as possible. In parallel to this, we recommend a number of other strategies be implemented including: reducing the appeal of all tobacco products, forbidding new tobacco products or brand variants being marketed without evidence of reduced harm, appeal or addictiveness, and developing a tobacco industry resourced, but industry independent, Framework Convention on Tobacco Control global repository to assist national regulators in understanding and regulating the products on their markets.

  15. 43 CFR 3931.70 - Production maps and production reports.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 43 Public Lands: Interior 2 2013-10-01 2013-10-01 false Production maps and production reports... EXPLORATION AND LEASES Plans of Development and Exploration Plans § 3931.70 Production maps and production... information to the MMS under 30 CFR parts 210 and 216. (c) Submit production maps to the proper BLM office...

  16. 43 CFR 3931.70 - Production maps and production reports.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 43 Public Lands: Interior 2 2012-10-01 2012-10-01 false Production maps and production reports... EXPLORATION AND LEASES Plans of Development and Exploration Plans § 3931.70 Production maps and production... information to the MMS under 30 CFR parts 210 and 216. (c) Submit production maps to the proper BLM office...

  17. Perspectives in production of functional meat products

    NASA Astrophysics Data System (ADS)

    Vasilev, D.; Glišić, M.; Janković, V.; Dimitrijević, M.; Karabasil, N.; Suvajdžić, B.; Teodorović, V.

    2017-09-01

    The meat industry has met new challenges since the World Health Organization classified processed meat in carcinogenic Group 1. In relation to this, the functional food concept in meat processing has gained importance, especially in reducing carcinogenic N-nitroso compounds and polycyclic aromatic hydrocarbons (PAHs) as an additional imperative, apart from the usual fat and salt reduction and product enrichment with functional ingredients. PAH reduction relies on control of the smoking process, but there is also a possibility they could be degraded by means of probiotic microorganisms or spices. The reduction of N-nitroso compounds could be provided by lowering the amount of added nitrite/nitrate, using substitutes for these chemicals, and/or by preventing conditions for the creation of N-nitroso compounds. Nevertheless, fat and salt reductions still remain topical, and rely mostly on the use of functional ingredients as their substitutes.

  18. Dairy products and cancer.

    PubMed

    Lampe, Johanna W

    2011-10-01

    Cancer is a group of more than 100 diseases in which cells display uncontrolled growth, invasion, and sometimes metastasis. Milk and dairy products contain micronutrients and several bioactive constituents that may influence cancer risk and progression. Much of the focus of human, population-based studies has been on the effects of intake of milk and total dairy products or of calcium intake. Based on a systematic review of the epidemiologic literature, the World Cancer Research Fund and American Institute for Cancer Research report concluded there was a probable association between milk intake and lower risk of colorectal cancer, a probable association between diets high in calcium and increased risk of prostate cancer, and limited evidence of an association between milk intake and lower risk of bladder cancer. For other cancers, the evidence was mixed or lacking. Since the 2007 report, several additional, large-cohort studies have been published, including two that show an inverse association between intake of cultured dairy products and bladder cancer. Little is known about the potential effect of various bioactives produced during rumen microbe metabolism on cancer risk. Furthermore, studies support a role of live microbes present in some dairy products in the modulation of the human gut microbial community and gut metabolism. Given the growing appreciation for the role of the gut microbial community in relation to immune function and health and disease, including cancer, the potential role of various dairy products in the modulation of the human gut microbiome warrants further evaluation. Key teaching points: As a dietary exposure, dairy products are a complex group of foods and composition varies by region, which makes evaluation of their association with disease risk difficult. For most cancers, associations between cancer risk and intake of milk and dairy products have been examined only in a small number of cohort studies, and data are inconsistent or

  19. Beauty production at CDF

    SciTech Connect

    Shears, Tara; /Liverpool U.

    2008-04-01

    A review of recent measurements of beauty production, based on proton antiproton collision data at {radical}s = 1.96 TeV and using the CDF detector, is given. Previous measurements of beauty (b) quark production at the Tevatron, carried out at centre-of-mass energies {radical}s = 1.8 TeV, have shown discrepancies when compared to Next to Leading Order (NLO) predictions [1]. Improved predictions and experimental procedures have reduced this discrepancy [2]. Improved parton density functions, better fragmentation functions and more complete theoretical calculations have improved theoretical accuracy. Experimentally, measurements of beauty production at {radical}s = 1.96 TeV are now presented in terms of b hadrons or B mesons, to avoid problems unfolding back to the quark level. In this review [3] measurements of inclusive beauty (where one beauty jet or hadron is reconstructed in the event), and beauty + X (where X can be a boson or another beauty jet or hadron), production will be presented: inclusive beauty jet cross-section; semi and fully reconstructed B meson cross-section; beauty dijet cross-section; semi-reconstructed B B meson cross-section; Z boson + beauty jet cross-section. More information concerning other measurements of heavy quark production can be found elsewhere [4].

  20. Technology's Impact on Production

    SciTech Connect

    Rachel Amann; Ellis Deweese; Deborah Shipman

    2009-06-30

    As part of a cooperative agreement with the United States Department of Energy (DOE) - entitled Technology's Impact on Production: Developing Environmental Solutions at the State and National Level - the Interstate Oil and Gas Compact Commission (IOGCC) has been tasked with assisting state governments in the effective, efficient, and environmentally sound regulation of the exploration and production of natural gas and crude oil, specifically in relation to orphaned and abandoned wells and wells nearing the end of productive life. Project goals include: (1) Developing (a) a model framework for prioritization and ranking of orphaned or abandoned well sites; (b) a model framework for disbursement of Energy Policy Act of 2005 funding; and (c) a research study regarding the current status of orphaned wells in the nation. (2) Researching the impact of new technologies on environmental protection from a regulatory perspective. Research will identify and document (a) state reactions to changing technology and knowledge; (b) how those reactions support state environmental conservation and public health; and (c) the impact of those reactions on oil and natural gas production. (3) Assessing emergent technology issues associated with wells nearing the end of productive life. Including: (a) location of orphaned and abandoned well sites; (b) well site remediation; (c) plugging materials; (d) plug placement; (e) the current regulatory environment; and (f) the identification of emergent technologies affecting end of life wells. New Energy Technologies - Regulating Change, is the result of research performed for Tasks 2 and 3.