Evaluation of DNA damage induced by Auger electrons from 137Cs.

PubMed

Watanabe, Ritsuko; Hattori, Yuya; Kai, Takeshi

2016-11-01

To understand the biological effect of external and internal exposure from 137 Cs, DNA damage spectrum induced by directly emitted electrons (γ-rays, internal conversion electrons, Auger electrons) from 137 Cs was compared with that induced by 137 Cs γ-rays. Monte Carlo track simulation method was used to calculate the microscopic energy deposition pattern in liquid water. Simulation was performed for the two simple target systems in microscale. Radiation sources were placed inside for one system and outside for another system. To simulate the energy deposition by directly emitted electrons from 137 Cs placed inside the system, the multiple ejections of electrons after internal conversion were considered. In the target systems, induction process of DNA damage was modeled and simulated for both direct energy deposition and the water radical reaction on the DNA. The yield and spatial distribution of simple and complex DNA damage including strand breaks and base lesions were calculated for irradiation by electrons and γ-rays from 137 Cs. The simulation showed that the significant difference in DNA damage spectrum was not caused by directly ejected electrons and γ-rays from 137 Cs. The result supports the existing perception that the biological effects by internal and external exposure by 137 Cs are equivalent.

Clustered DNA damages induced by high and low LET radiation, including heavy ions

NASA Technical Reports Server (NTRS)

Sutherland, B. M.; Bennett, P. V.; Schenk, H.; Sidorkina, O.; Laval, J.; Trunk, J.; Monteleone, D.; Sutherland, J.; Lowenstein, D. I. (Principal Investigator)

2001-01-01

Clustered DNA damages--here defined as two or more lesions (strand breaks, oxidized purines, oxidized pyrimidines or abasic sites) within a few helical turns--have been postulated as difficult to repair accurately, and thus highly significant biological lesions. Further, attempted repair of clusters may produce double strand breaks (DSBs). However, until recently, there was no way to measure ionizing radiation-induced clustered damages, except DSB. We recently described an approach for measuring classes of clustered damages (oxidized purine clusters, oxidized pyrimidine clusters, abasic clusters, along with DSB). We showed that ionizing radiation (gamma rays and Fe ions, 1 GeV/amu) does induce such clusters in genomic DNA in solution and in human cells. These studies also showed that each damage cluster results from one radiation hit (and its track), thus indicating that they can be induced by very low doses of radiation, i.e. two independent hits are not required for cluster induction. Further, among all complex damages, double strand breaks comprise--at most-- 20%, with the other clustered damages being at least 80%.

Track Structure and the Biological Effectiveness of Accelerated Particles for the Induction of Chromosome Damage

NASA Technical Reports Server (NTRS)

George, K.; Hada, M.; Chappell, L.; Cucinotta, F. A.

2011-01-01

Track structure models predict that at a fixed value of LET, particles with lower charge number, Z will have a higher biological effectiveness compared to particles with a higher Z. In this report we investigated how track structure effects induction of chromosomal aberration in human cells. Human lymphocytes were irradiated in vitro with various energies of accelerated iron, silicon, neon, or titanium ions and chromosome damage was assessed in using three color FISH chromosome painting in chemically induced PCC samples collected a first cell division post irradiation. The LET values for these ions ranged from 30 to195 keV/micron. Of the particles studied, Neon ions have the highest biological effectiveness for induction of total chromosome damage, which is consistent with track structure model predictions. For complex-type exchanges 64 MeV/ u Neon and 450 MeV/u Iron were equally effective and induced the most complex damage. In addition we present data on chromosomes exchanges induced by six different energies of protons (5 MeV/u to 2.5 GeV/u). The linear dose response term was similar for all energies of protons suggesting that the effect of the higher LET at low proton energies is balanced by the production of nuclear secondaries from the high energy protons.

DETECTION OF LOW DOSE RADIATION-AND CHEMICALLY-INDUCED DNA DAMAGE USING TEMPERATURE DIFFERENTIAL FLUORESCENCE ASSAYS

EPA Science Inventory

Rapid, sensitive and simple assays for radiation- and chemically-induced DNA damage can be of significant benefit to a number of fields including radiation biology, clinical research, and environmental monitoring. Although temperature-induced DNA strand separation has been use...

Complex DNA Damage: A Route to Radiation-Induced Genomic Instability and Carcinogenesis.

PubMed

Mavragani, Ifigeneia V; Nikitaki, Zacharenia; Souli, Maria P; Aziz, Asef; Nowsheen, Somaira; Aziz, Khaled; Rogakou, Emmy; Georgakilas, Alexandros G

2017-07-18

Cellular effects of ionizing radiation (IR) are of great variety and level, but they are mainly damaging since radiation can perturb all important components of the cell, from the membrane to the nucleus, due to alteration of different biological molecules ranging from lipids to proteins or DNA. Regarding DNA damage, which is the main focus of this review, as well as its repair, all current knowledge indicates that IR-induced DNA damage is always more complex than the corresponding endogenous damage resulting from endogenous oxidative stress. Specifically, it is expected that IR will create clusters of damage comprised of a diversity of DNA lesions like double strand breaks (DSBs), single strand breaks (SSBs) and base lesions within a short DNA region of up to 15-20 bp. Recent data from our groups and others support two main notions, that these damaged clusters are: (1) repair resistant, increasing genomic instability (GI) and malignant transformation and (2) can be considered as persistent "danger" signals promoting chronic inflammation and immune response, causing detrimental effects to the organism (like radiation toxicity). Last but not least, the paradigm shift for the role of radiation-induced systemic effects is also incorporated in this picture of IR-effects and consequences of complex DNA damage induction and its erroneous repair.

[The role of the biological damaging factor in the explosive injury].

PubMed

Popov, V L; Kadochnikov, D S; Minaeva, P V

2015-01-01

This article describes the specific features of the action of the biological damaging factors on the human organism associated with the explosive injury. Both the direct action of the damaging agents contained in the biological weapons and their secondary effects in the form of systemic and local infectious complications of the inflicted wounds are considered. The criteria for the evaluation of the degree of harm to the health of the victims of explosion attributable to the action of the biological damaging factor are proposed.

CDP-choline circumvents mercury-induced mitochondrial damage and renal dysfunction.

PubMed

Buelna-Chontal, Mabel; Franco, Martha; Hernández-Esquivel, Luz; Pavón, Natalia; Rodríguez-Zavala, José S; Correa, Francisco; Jasso, Ricardo; Pichardo-Ramos, Gregorio; Santamaría, José; González-Pacheco, Héctor; Soto, Virgilia; Díaz-Ruíz, Jorge L; Chávez, Edmundo

2017-12-01

Heavy metal ions are known to produce harmful alterations on kidney function. Specifically, the accumulation of Hg 2+ in kidney tissue may induce renal failure. In this work, the protective effect of CDP-choline against the deleterious effects induced by Hg 2+ on renal function was studied. CDP-choline administered ip at a dose of 125 mg/kg body weight prevented the damage induced by Hg 2+ administration at a dose of 3 mg/kg body weight. The findings indicate that CDP-choline guards mitochondria against Hg 2+ -toxicity by preserving their ability to retain matrix content, such as accumulated Ca 2+ . This nucleotide also protected mitochondria from Hg 2+ -induced loss of the transmembrane electric gradient and from the generation of hydrogen peroxide and membrane TBARS. In addition, CDP-choline avoided the oxidative damage of mtDNA and inhibited the release of the interleukins IL-1 and IL6, recognized as markers of acute inflammatory reaction. After the administration of Hg 2+ and CDP, CDP-choline maintained nearly normal levels of renal function and creatinine clearance, as well as blood urea nitrogen (BUN) and serum creatinine. © 2017 International Federation for Cell Biology.

Inflammation-Induced Cell Proliferation Potentiates DNA Damage-Induced Mutations In Vivo

PubMed Central

Kiraly, Orsolya; Gong, Guanyu; Olipitz, Werner; Muthupalani, Sureshkumar; Engelward, Bevin P.

2015-01-01

Mutations are a critical driver of cancer initiation. While extensive studies have focused on exposure-induced mutations, few studies have explored the importance of tissue physiology as a modulator of mutation susceptibility in vivo. Of particular interest is inflammation, a known cancer risk factor relevant to chronic inflammatory diseases and pathogen-induced inflammation. Here, we used the fluorescent yellow direct repeat (FYDR) mice that harbor a reporter to detect misalignments during homologous recombination (HR), an important class of mutations. FYDR mice were exposed to cerulein, a potent inducer of pancreatic inflammation. We show that inflammation induces DSBs (γH2AX foci) and that several days later there is an increase in cell proliferation. While isolated bouts of inflammation did not induce HR, overlap between inflammation-induced DNA damage and inflammation-induced cell proliferation induced HR significantly. To study exogenously-induced DNA damage, animals were exposed to methylnitrosourea, a model alkylating agent that creates DNA lesions relevant to both environmental exposures and cancer chemotherapy. We found that exposure to alkylation damage induces HR, and importantly, that inflammation-induced cell proliferation and alkylation induce HR in a synergistic fashion. Taken together, these results show that, during an acute bout of inflammation, there is a kinetic barrier separating DNA damage from cell proliferation that protects against mutations, and that inflammation-induced cell proliferation greatly potentiates exposure-induced mutations. These studies demonstrate a fundamental mechanism by which inflammation can act synergistically with DNA damage to induce mutations that drive cancer and cancer recurrence. PMID:25647331

Clustered DNA damages induced in isolated DNA and in human cells by low doses of ionizing radiation

NASA Technical Reports Server (NTRS)

Sutherland, B. M.; Bennett, P. V.; Sidorkina, O.; Laval, J.; Lowenstein, D. I. (Principal Investigator)

2000-01-01

Clustered DNA damages-two or more closely spaced damages (strand breaks, abasic sites, or oxidized bases) on opposing strands-are suspects as critical lesions producing lethal and mutagenic effects of ionizing radiation. However, as a result of the lack of methods for measuring damage clusters induced by ionizing radiation in genomic DNA, neither the frequencies of their production by physiological doses of radiation, nor their repairability, nor their biological effects are known. On the basis of methods that we developed for quantitating damages in large DNAs, we have devised and validated a way of measuring ionizing radiation-induced clustered lesions in genomic DNA, including DNA from human cells. DNA is treated with an endonuclease that induces a single-strand cleavage at an oxidized base or abasic site. If there are two closely spaced damages on opposing strands, such cleavage will reduce the size of the DNA on a nondenaturing gel. We show that ionizing radiation does induce clustered DNA damages containing abasic sites, oxidized purines, or oxidized pyrimidines. Further, the frequency of each of these cluster classes is comparable to that of frank double-strand breaks; among all complex damages induced by ionizing radiation, double-strand breaks are only about 20%, with other clustered damage constituting some 80%. We also show that even low doses (0.1-1 Gy) of high linear energy transfer ionizing radiation induce clustered damages in human cells.

Complex DNA Damage: A Route to Radiation-Induced Genomic Instability and Carcinogenesis

PubMed Central

Mavragani, Ifigeneia V.; Nikitaki, Zacharenia; Souli, Maria P.; Aziz, Asef; Nowsheen, Somaira; Aziz, Khaled; Rogakou, Emmy

2017-01-01

Cellular effects of ionizing radiation (IR) are of great variety and level, but they are mainly damaging since radiation can perturb all important components of the cell, from the membrane to the nucleus, due to alteration of different biological molecules ranging from lipids to proteins or DNA. Regarding DNA damage, which is the main focus of this review, as well as its repair, all current knowledge indicates that IR-induced DNA damage is always more complex than the corresponding endogenous damage resulting from endogenous oxidative stress. Specifically, it is expected that IR will create clusters of damage comprised of a diversity of DNA lesions like double strand breaks (DSBs), single strand breaks (SSBs) and base lesions within a short DNA region of up to 15–20 bp. Recent data from our groups and others support two main notions, that these damaged clusters are: (1) repair resistant, increasing genomic instability (GI) and malignant transformation and (2) can be considered as persistent “danger” signals promoting chronic inflammation and immune response, causing detrimental effects to the organism (like radiation toxicity). Last but not least, the paradigm shift for the role of radiation-induced systemic effects is also incorporated in this picture of IR-effects and consequences of complex DNA damage induction and its erroneous repair. PMID:28718816

Noise Induced DNA Damage Within the Auditory Nerve.

PubMed

Guthrie, O'neil W

2017-03-01

An understanding of the molecular pathology that underlies noise induced neurotoxicity is a prerequisite to the design of targeted therapies. The objective of the current experiment was to determine whether or not DNA damage is part of the pathophysiologic sequela of noise induced neurotoxicity. The experiment consisted of 41 hooded Long-Evans rats (2 month old males) that were randomized into control and noise exposed groups. Both the control and the noise group followed the same time schedule and therefore started and ended the experiment together. The noise dose consisted of a 6000 Hz noise band at 105 dB SPL. Temporal bones from both groups were harvested, and immunohistochemistry was used to identify neurons with DNA damage. Quantitative morphometric analyses was then employed to determine the level of DNA damage. Neural action potentials were recorded to assess the functional impact of noise induced DNA damage. Immunohistochemical reactions revealed that the noise exposure precipitated DNA damage within the nucleus of auditory neurons. Quantitative morphometry confirmed the noise induced increase in DNA damage levels and the precipitation of DNA damage was associated with a significant loss of nerve sensitivity. Therefore, DNA damage is part of the molecular pathology that drives noise induced neurotoxicity. Anat Rec, 300:520-526, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Skin protection against UVA-induced iron damage by multiantioxidants and iron chelating drugs/prodrugs.

PubMed

Reelfs, Olivier; Eggleston, Ian M; Pourzand, Charareh

2010-03-01

In humans, prolonged sunlight exposure is associated with various pathological states. The continuing drive to develop improved skin protection involves not only approaches to reduce DNA damage by solar ultraviolet B (UVB) but also the development of methodologies to provide protection against ultraviolet A (UVA), the oxidising component of sunlight. Furthermore identification of specific cellular events following ultraviolet (UV) irradiation is likely to provide clues as to the mechanism of the development of resulting pathologies and therefore strategies for protection. Our discovery that UVA radiation, leads to an immediate measurable increase in 'labile' iron in human skin fibroblasts and keratinocytes provides a new insight into UVA-induced skin damage, since iron is a catalyst of biological oxidations. The main purpose of this overview is to bring together some of the new findings related to mechanisms underlying UVA-induced iron release and to discuss novel approaches based on the use of multiantioxidants and light-activated caged-iron chelators for efficient protection of skin cells against UVA-induced iron damage.

Drug-induced corneal damage.

PubMed

2014-04-01

Corneal damage can have a variety of causes, including infections, chemical splashes, environmental factors (radiation, trauma, contact lenses, etc.), and systemic diseases (genetic, autoimmune, inflammatory, metabolic, etc.). A wide range of drugs can also damage the cornea. The severity of drug-induced corneal changes can range from simple asymptomatic deposits to irreversible, sight-threatening damage. Several factors can influence the onset of corneal lesions. Some factors, such as the dose, are treatment-related, while others such as contact lenses, are patient-related. A variety of mechanisms may be involved, including corneal dryness, changes in the corneal epithelium, impaired wound healing and deposits. Many drugs can damage the cornea through direct contact, after intraocular injection or instillation, including VEGF inhibitors, anti-inflammatory drugs, local anaesthetics, glaucoma drugs, fluoroquinolones, and preservatives. Some systemically administered drugs can also damage the cornea, notably cancer drugs, amiodarone and isotretinoin. Vulnerable patients should be informed of this risk if they are prescribed a drug with the potential to damage the cornea so that they can identify problems in a timely manner. It may be necessary to discontinue the suspect drug when signs and symptoms of corneal damage occur.

The protective effect of grape seed procyanidin extract against cadmium-induced renal oxidative damage in mice.

PubMed

Chen, Qing; Zhang, Rong; Li, Wei-min; Niu, Yu-jie; Guo, Hui-cai; Liu, Xue-hui; Hou, Yu-chun; Zhao, Li-juan

2013-11-01

As an important environmental pollutant, cadmium (Cd) can lead to serious renal damage. Grape seed procyanidins extract (GSPE), a biological active component of grape seed, has been shown to possess antioxidative effects. Here, we assessed the protective effect of GSPE on Cd-induced renal damage using animal experiment. After 30 days, the oxidative damage of kidney was evaluated through measurement of superoxide dismutase (SOD), glutathione peroxidation (GSH-Px) and malondialdehyde (MDA). Since, oxidative stress could lead to apoptosis, the renal apoptosis was measured using flow cytometer. Moreover, the expression of apoptosis-related protein Bax and Bcl-2 was analyzed by immunohistochemistry and Western blot. The results showed that Cd led to the decrease of SOD and GSH-Px activities, and the increase of MDA level, induced renal apoptosis. However, the coadministration of GSPE attenuated Cd-induced lipid peroxidation, and antagonized renal apoptosis, probably associated with the expression of Bax and Bcl-2. These data suggested that GSPE has protective effect against renal oxidative damage induced by Cd, which provide a potential natural chemopreventive agent against Cd-poisoning. Copyright © 2013 Elsevier B.V. All rights reserved.

Cytoprotective effect against UV-induced DNA damage and oxidative stress: role of new biological UV filter.

PubMed

Said, T; Dutot, M; Martin, C; Beaudeux, J-L; Boucher, C; Enee, E; Baudouin, C; Warnet, J-M; Rat, P

2007-03-01

The majority of chemical solar filters are cytotoxic, particularly on sensitive ocular cells (corneal and conjunctival cells). Consequently, a non-cytotoxic UV filter would be interesting in dermatology, but more especially in ophthalmology. In fact, light damage to the eye can be avoided thanks to a very efficient ocular antioxidant system; indeed, the chromophores absorb light and dissipate its energy. After middle age, a decrease in the production of antioxidants and antioxidative enzymes appears with accumulation of endogenous molecules that are phototoxic. UV radiations can induce reactive oxygen species formation, leading to various ocular diseases. Because most UV filters are cytotoxic for the eye, we investigated the anti-UV properties of Calophyllum inophyllum oil in order to propose it as a potential vehicle, free of toxicity, with a natural UV filter action in ophthalmic formulation. Calophyllum inophyllum oil, even at low concentration (1/10,000, v/v), exhibited significant UV absorption properties (maximum at 300nm) and was associated with an important sun protection factor (18-22). Oil concentrations up to 1% were not cytotoxic on human conjunctival epithelial cells, and Calophyllum inophyllum oil appeared to act as a cytoprotective agent against oxidative stress and DNA damage (85% of the DNA damage induced by UV radiations were inhibited with 1% Calophyllum oil) and did not induce in vivo ocular irritation (Draize test on New Zealand rabbits). Calophyllum inophyllum oil thus exhibited antioxidant and cytoprotective properties, and therefore might serve, for the first time, as a natural UV filter in ophthalmic preparations.

BRAIN DAMAGE IN CHILDREN, THE BIOLOGICAL AND SOCIAL ASPECTS.

ERIC Educational Resources Information Center

BIRCH, HERBERT G., ED.

PAPERS AND DISCUSSION SUMMARIES ARE PRESENTED FROM A CONFERENCE ON THE BIOLOGICAL AND SOCIAL PROBLEMS OF CHILDHOOD BRAIN DAMAGE, HELD AT THE CHILDREN'S HOSPITAL OF PHILADELPHIA IN NOVEMBER 1962. A VARIETY OF DISCIPLINES IS REPRESENTED, AND THE FOLLOWING TOPICS ARE CONSIDERED--(1) "THE PROBLEM OF 'BRAIN DAMAGE' IN CHILDREN" BY HERBERT G. BIRCH, (2)…

Quercitrin protects skin from UVB-induced oxidative damage

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yin, Yuanqin; Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY; Li, Wenqi

Exposure of the skin to ultraviolet B (UVB) radiation causes oxidative damage to skin, resulting in sunburn, photoaging, and skin cancer. It is generally believed that the skin damage induced by UV irradiation is a consequence of generation of reactive oxygen species (ROS). Recently, there is an increased interest in the use of natural products as chemopreventive agents for non-melanoma skin cancer (NMSC) due to their antioxidants and anti-inflammatory properties. Quercitrin, glycosylated form of quercetin, is the most common flavonoid in nature with antioxidant properties. The present study investigated the possible beneficial effects of quercitrin to inhibit UVB irradiation-induced oxidativemore » damage in vitro and in vivo. Our results showed that quercitrin decreased ROS generation induced by UVB irradiation in JB6 cells. Quercitrin restored catalase expression and GSH/GSSG ratio reduced by UVB exposure, two major antioxidant enzymes, leading to reductions of oxidative DNA damage and apoptosis and protection of the skin from inflammation caused by UVB exposure. The present study demonstrated that quercitrin functions as an antioxidant against UVB irradiation-induced oxidative damage to skin. - Highlights: • Oxidative stress plays a key role in UV-induced cell and tissue injuries. • Quercitrin decreases ROS generation and restores antioxidants irradiated by UVB. • Quercitrin reduces UVB-irradiated oxidative DNA damage, apoptosis, and inflammation. • Quercitrin functions as an antioxidant against UVB-induced skin injuries.« less

Genetic damage induced by organic extract of coke oven emissions on human bronchial epithelial cells.

PubMed

Zhai, Qingfeng; Duan, Huawei; Wang, Yadong; Huang, Chuanfeng; Niu, Yong; Dai, Yufei; Bin, Ping; Liu, Qingjun; Chen, Wen; Ma, Junxiang; Zheng, Yuxin

2012-08-01

Coke oven emissions are known as human carcinogen, which is a complex mixture of polycyclic aromatic hydrocarbon. In this study, we aimed to clarify the mechanism of action of coke oven emissions induced carcinogenesis and to identify biomarkers of early biological effects in a human bronchial epithelial cell line with CYP1A1 activity (HBE-CYP1A1). Particulate matter was collected in the oven area on glass filter, extracted and analyzed by GC/MS. DNA breaks and oxidative damage were evaluated by alkaline and endonucleases (FPG, hOGG1 and ENDO III)-modified comet assays. Cytotoxicity and chromosomal damage were assessed by the cytokinesis-block micronucleus cytome (CBMN-Cyt) assay. The cells were treated with organic extract of coke oven emissions (OE-COE) representing 5, 10, 20, 40μg/mL extract for 24h. We found that there was a dose-effect relationship between the OE-COE and the direct DNA damage presented by tail length, tail intensity and Olive tail moment in the comet assay. The presence of lesion-specific endonucleases in the assays increased DNA migration after OE-COE treatment when compared to those without enzymes, which indicated that OE-COE produced oxidative damage at the level of pyrimidine and purine bases. The dose-dependent increase of micronuclei, nucleoplasmic bridges and nuclear buds in exposed cells was significant, indicating chromosomal and genomic damage induced by OE-COE. Based on the cytotoxic biomarkers in CBMN-Cyt assay, OE-COE may inhibit nuclear division, interfere with apoptosis, or induce cell necrosis. This study indicates that OE-COE exposure can induce DNA breaks/oxidative damage and genomic instability in HBE-CYP1A1 cells. The FPG-comet assay appears more specific for detecting oxidative DNA damage induced by complex mixtures of genotoxic substances. Copyright © 2012 Elsevier Ltd. All rights reserved.

Quercitrin Protects Skin from UVB-induced Oxidative Damage

PubMed Central

Yin, Yuanqin; Li, Wenqi; Son, Yong-Ok; Sun, Lijuan; Lu, Jian; Kim, Donghern; Wang, Xin; Yao, Hua; Wang, Lei; Pratheeshkumar, Poyil; Hitron, Andrew J; Luo, Jia; Gao, Ning; Shi, Xianglin; Zhang, Zhuo

2013-01-01

Exposure of the skin to ultraviolet B (UVB) radiation causes oxidative damage to skin, resulting in sunburn, photoaging, and skin cancer. It is generally believed that the skin damage induced by UV irradiation is a consequence of generation of reactive oxygen species (ROS). Recently, there is an increased interest in the use of natural products as chemopreventive agents for non-melanoma skin cancer (NMSC) due to their antioxidants and anti-inflammatory properties. Quercitrin, glycosylated form of quercetin, is the most common flavonoid in nature with antioxidant properties. The present study investigated the possible beneficial effects of quercitrin to inhibit UVB irradiation-induced oxidative damage in vitro and in vivo. Our results showed that quercitrin decreased ROS generation induced by UVB irradiation in JB6 cells. Quercitrin restored catalase expression and GSH/GSSG ratio reduced by UVB exposure, two major antioxidant enzymes, leading to reductions of oxidative DNA damage and apoptosis and protection of the skin from inflammation caused by UVB exposure. The present study demonstrated that quercitrin functions as an antioxidant against UVB irradiation-induced oxidative damage to skin. PMID:23545178

Renal tissue damage induced by focused shock waves

NASA Astrophysics Data System (ADS)

Ioritani, N.; Kuwahara, M.; Kambe, K.; Taguchi, K.; Saitoh, T.; Shirai, S.; Orikasa, S.; Takayama, K.; Lush, P. A.

1990-07-01

Biological evidence of renal arterial wall damage induced by the microjet due to shock wave-cavitation bubble interaction was demonstrated in living dog kidneys. We also intended to clarify the mechanism of renal tissue damage and the effects of different conditions of shock wave exposure (peak pressure of focused area, number of shots, exposure rate) on the renal tissue damage in comparison to stone disintegration. Disruption of arterial wall was the most remarkable histological change in the focused area of the kidneys. This lesion appeared as if the wall had been punctured by a needle. Large hematoma formation in the renal parenchym, and interstitial hemorrhage seemed to be the results of the arterial lesion. This arterial disorder also led to ischemic necrosis of the tubules surrounding the hematoma. Micro-angiographic examination of extracted kidneys also proved such arterial puncture lesions and ischemic lesions. The number of shots required for model stone disintegration was not inversely proportional to peak pressure. It decreased markedly when peak pressure was above 700 bar. Similarly thenumber of shots for hematoma formation was not inversely proportional to peak pressure, however, this decreased markedly above 500 bar. These results suggested that a hematoma could be formed under a lower peak pressure than that required for stone disintegration.

Repair of DNA damage induced by accelerated heavy ions--a mini review.

PubMed

Okayasu, Ryuichi

2012-03-01

Increasing use of heavy ions for cancer therapy and concerns from exposure to heavy charged particles in space necessitate the study of the basic biological mechanisms associated with exposure to heavy ions. As the most critical damage induced by ionizing radiation is DNA double strand break (DSB), this review focuses on DSBs induced by heavy ions and their repair processes. Compared with X- or gamma-rays, high-linear energy transfer (LET) heavy ion radiation induces more complex DNA damage, categorized into DSBs and non-DSB oxidative clustered DNA lesions (OCDL). This complexity makes the DNA repair process more difficult, partially due to retarded enzymatic activities, leading to increased chromosome aberrations and cell death. In general, the repair process following heavy ion exposure is LET-dependent, but with nonhomologous end joining defective cells, this trend is less emphasized. The variation in cell survival levels throughout the cell cycle is less prominent in cells exposed to high-LET heavy ions when compared with low LET, but this mechanism has not been well understood until recently. Involvement of several DSB repair proteins is suggested to underlie this interesting phenomenon. Recent improvements in radiation-induced foci studies combined with high-LET heavy ion exposure could provide a useful opportunity for more in depth study of DSB repair processes. Accelerated heavy ions have become valuable tools to investigate the molecular mechanisms underlying repair of DNA DSBs, the most crucial form of DNA damage induced by radiation and various chemotherapeutic agents. Copyright © 2011 UICC.

Recruitment of TRF2 to laser-induced DNA damage sites.

PubMed

Huda, Nazmul; Abe, Satoshi; Gu, Ling; Mendonca, Marc S; Mohanty, Samarendra; Gilley, David

2012-09-01

Several lines of evidence suggest that the telomere-associated protein TRF2 plays critical roles in the DNA damage response. TRF2 is rapidly and transiently phosphorylated by an ATM-dependent pathway in response to DNA damage and this DNA damage-induced phosphoryation is essential for the DNA-PK-dependent pathway of DNA double-strand break repair (DSB). However, the type of DNA damage that induces TRF2 localization to the damage sites, the requirement for DNA damage-induced phosphorylation of TRF2 for its recruitment, as well as the detailed kinetics of TRF2 accumulation at DNA damage sites have not been fully investigated. In order to address these questions, we used an ultrafast femtosecond multiphoton laser and a continuous wave 405-nm single photon laser to induce DNA damage at defined nuclear locations. Our results showed that DNA damage produced by a femtosecond multiphoton laser was sufficient for localization of TRF2 to these DNA damage sites. We also demonstrate that ectopically expressed TRF2 was recruited to DNA lesions created by a 405-nm laser. Our data suggest that ATM and DNA-PKcs kinases are not required for TRF2 localization to DNA damage sites. Furthermore, we found that phosphorylation of TRF2 at residue T188 was not essential for its recruitment to laser-induced DNA damage sites. Thus, we provide further evidence that a protein known to function in telomere maintenance, TRF2, is recruited to sites of DNA damage and plays critical roles in the DNA damage response. Copyright © 2012 Elsevier Inc. All rights reserved.

Melatonin Role in Ameliorating Radiation-induced Skin Damage: From Theory to Practice (A Review of Literature).

PubMed

Abbaszadeh, A; Haddadi, G H; Haddadi, Z

2017-06-01

Normal skin is composed of epidermis and dermis. Skin is susceptible to radiation damage because it is a continuously renewing organ containing rapidly proliferating mature cells. Radiation burn is a damage to the skin or other biological tissues caused by exposure to radiofrequency energy or ionizing radiation. Acute skin reaction is the most frequently occurring side effect of radiation therapy. Generally, any chemical/biological agent given before or at the time of irradiation to prevent or ameliorate damage to normal tissues is called a radioprotector. Melatonin is a highly lipophilic substance that easily penetrates organic membranes and therefore is able to protect important intracellular structures including mitochondria and DNA against oxidative damage directly at the sites where such a kind of damage would occur. Melatonin leads to an increase in the molecular level of some important antioxidative enzymes such as superoxide, dismotase and glutation-peroxidase, and also a reduction in synthetic activity of nitric oxide. There is a large body of evidence which proves the efficacy of Melatonin in ameliorating UV and X ray-induced skin damage. We propose that, in the future, Melatonin would improve the therapeutic ratio in radiation oncology and ameliorate skin damage more effectively when administered in optimal and non-toxic doses.

Melatonin Role in Ameliorating Radiation-induced Skin Damage: From Theory to Practice (A Review of Literature)

PubMed Central

Abbaszadeh, A.; Haddadi, G.H.; Haddadi, Z.

2017-01-01

Normal skin is composed of epidermis and dermis. Skin is susceptible to radiation damage because it is a continuously renewing organ containing rapidly proliferating mature cells. Radiation burn is a damage to the skin or other biological tissues caused by exposure to radiofrequency energy or ionizing radiation. Acute skin reaction is the most frequently occurring side effect of radiation therapy. Generally, any chemical/biological agent given before or at the time of irradiation to prevent or ameliorate damage to normal tissues is called a radioprotector. Melatonin is a highly lipophilic substance that easily penetrates organic membranes and therefore is able to protect important intracellular structures including mitochondria and DNA against oxidative damage directly at the sites where such a kind of damage would occur. Melatonin leads to an increase in the molecular level of some important antioxidative enzymes such as superoxide, dismotase and glutation-peroxidase, and also a reduction in synthetic activity of nitric oxide. There is a large body of evidence which proves the efficacy of Melatonin in ameliorating UV and X ray-induced skin damage. We propose that, in the future, Melatonin would improve the therapeutic ratio in radiation oncology and ameliorate skin damage more effectively when administered in optimal and non-toxic doses. PMID:28580334

Quercitrin protects skin from UVB-induced oxidative damage.

PubMed

Yin, Yuanqin; Li, Wenqi; Son, Young-Ok; Sun, Lijuan; Lu, Jian; Kim, Donghern; Wang, Xin; Yao, Hua; Wang, Lei; Pratheeshkumar, Poyil; Hitron, Andrew J; Luo, Jia; Gao, Ning; Shi, Xianglin; Zhang, Zhuo

2013-06-01

Exposure of the skin to ultraviolet B (UVB) radiation causes oxidative damage to skin, resulting in sunburn, photoaging, and skin cancer. It is generally believed that the skin damage induced by UV irradiation is a consequence of generation of reactive oxygen species (ROS). Recently, there is an increased interest in the use of natural products as chemopreventive agents for non-melanoma skin cancer (NMSC) due to their antioxidants and anti-inflammatory properties. Quercitrin, glycosylated form of quercetin, is the most common flavonoid in nature with antioxidant properties. The present study investigated the possible beneficial effects of quercitrin to inhibit UVB irradiation-induced oxidative damage in vitro and in vivo. Our results showed that quercitrin decreased ROS generation induced by UVB irradiation in JB6 cells. Quercitrin restored catalase expression and GSH/GSSG ratio reduced by UVB exposure, two major antioxidant enzymes, leading to reductions of oxidative DNA damage and apoptosis and protection of the skin from inflammation caused by UVB exposure. The present study demonstrated that quercitrin functions as an antioxidant against UVB irradiation-induced oxidative damage to skin. Copyright © 2013 Elsevier Inc. All rights reserved.

An Investigation of Laser Induced Surface Damage in glass.

DTIC Science & Technology

1985-06-01

ROA-RI60 669 RN INVESTIGATION OF LASER INDUCED SURFACE DAMAG IN In1 1 6lo GLASS (U) NAVAL POSTGRADUATE SCHOOL MONTEREY CA R D UYAK JUN 85IUNCLASSIFIED...ii -0 NAVAL POSTGRADUATE SCHOOL Monterey, California bor OCT THESIS AN INVESTIGATION OF LASER INDUCED SURFACE DAMAGE IN GLASS by )Richard David Uyak ,L...Subtitle) EPORT 6 PERIOD COVERED %An Investigation of Laser Induced Master’s Thesis Surface Damage in Glass June 1985S. PERFORMING ORG. REPORT MUMMER 7

DNA-damage response during mitosis induces whole-chromosome missegregation.

PubMed

Bakhoum, Samuel F; Kabeche, Lilian; Murnane, John P; Zaki, Bassem I; Compton, Duane A

2014-11-01

Many cancers display both structural (s-CIN) and numerical (w-CIN) chromosomal instabilities. Defective chromosome segregation during mitosis has been shown to cause DNA damage that induces structural rearrangements of chromosomes (s-CIN). In contrast, whether DNA damage can disrupt mitotic processes to generate whole chromosomal instability (w-CIN) is unknown. Here, we show that activation of the DNA-damage response (DDR) during mitosis selectively stabilizes kinetochore-microtubule (k-MT) attachments to chromosomes through Aurora-A and PLK1 kinases, thereby increasing the frequency of lagging chromosomes during anaphase. Inhibition of DDR proteins, ATM or CHK2, abolishes the effect of DNA damage on k-MTs and chromosome segregation, whereas activation of the DDR in the absence of DNA damage is sufficient to induce chromosome segregation errors. Finally, inhibiting the DDR during mitosis in cancer cells with persistent DNA damage suppresses inherent chromosome segregation defects. Thus, the DDR during mitosis inappropriately stabilizes k-MTs, creating a link between s-CIN and w-CIN. The genome-protective role of the DDR depends on its ability to delay cell division until damaged DNA can be fully repaired. Here, we show that when DNA damage is induced during mitosis, the DDR unexpectedly induces errors in the segregation of entire chromosomes, thus linking structural and numerical chromosomal instabilities. ©2014 American Association for Cancer Research.

Curculigo orchioides protects cisplatin-induced cell damage.

PubMed

Kang, Tong Ho; Hong, Bin Na; Jung, Su-Young; Lee, Jeong-Han; So, Hong-Seob; Park, Raekil; You, Yong-Ouk

2013-01-01

Cisplatin is commonly used as a chemotherapeutic agent against many human cancers. However, it generates reactive oxygen species (ROS) and has serious dose-limiting side effects, including ototoxicity. The roots of Curculigo orchioides (C. orchioides) have been used to treat auditory diseases such as tinnitus and hearing loss in Chinese traditional medicine. In the present study, we investigated the protective effects of an ethanol extract obtained from C. orchioides rhizome (COR) on cisplatin-induced cell damage in auditory cells (HEI-OC1). COR (2.5-25 μg/ml) inhibited cisplatin-induced HEI-OC1 cell damage in a dose-dependent manner. To investigate the protective mechanism of COR on cisplatin cytotoxicity in HEI-OC1 cells, we measured the effects of COR on ROS generation and lipid peroxidation in cisplatin-treated cells as well as its scavenging activities against superoxide radicals, hydroxyl radicals, hydrogen peroxide, and DPPH radicals. COR (1-25 μg/ml) had scavenging activities against superoxide radicals, hydroxyl radicals, hydrogen peroxide, and DPPH radicals, as well as reduced lipid peroxidation. In in vivo experiments, COR was shown to reduce cochlear and peripheral auditory function impairments through cisplatin-induced auditory damage in mice. These results indicate that COR protects from cisplatin-induced auditory damage by inhibiting lipid peroxidation and scavenging activities against free radicals.

Radiation-induced DNA-protein cross-links: Mechanisms and biological significance.

PubMed

Nakano, Toshiaki; Xu, Xu; Salem, Amir M H; Shoulkamy, Mahmoud I; Ide, Hiroshi

2017-06-01

Ionizing radiation produces various DNA lesions such as base damage, DNA single-strand breaks (SSBs), DNA double-strand breaks (DSBs), and DNA-protein cross-links (DPCs). Of these, the biological significance of DPCs remains elusive. In this article, we focus on radiation-induced DPCs and review the current understanding of their induction, properties, repair, and biological consequences. When cells are irradiated, the formation of base damage, SSBs, and DSBs are promoted in the presence of oxygen. Conversely, that of DPCs is promoted in the absence of oxygen, suggesting their importance in hypoxic cells, such as those present in tumors. DNA and protein radicals generated by hydroxyl radicals (i.e., indirect effect) are responsible for DPC formation. In addition, DPCs can also be formed from guanine radical cations generated by the direct effect. Actin, histones, and other proteins have been identified as cross-linked proteins. Also, covalent linkages between DNA and protein constituents such as thymine-lysine and guanine-lysine have been identified and their structures are proposed. In irradiated cells and tissues, DPCs are repaired in a biphasic manner, consisting of fast and slow components. The half-time for the fast component is 20min-2h and that for the slow component is 2-70h. Notably, radiation-induced DPCs are repaired more slowly than DSBs. Homologous recombination plays a pivotal role in the repair of radiation-induced DPCs as well as DSBs. Recently, a novel mechanism of DPC repair mediated by a DPC protease was reported, wherein the resulting DNA-peptide cross-links were bypassed by translesion synthesis. The replication and transcription of DPC-bearing reporter plasmids are inhibited in cells, suggesting that DPCs are potentially lethal lesions. However, whether DPCs are mutagenic and induce gross chromosomal alterations remains to be determined. Copyright © 2017 Elsevier Inc. All rights reserved.

The small molecule calactin induces DNA damage and apoptosis in human leukemia cells.

PubMed

Lee, Chien-Chih; Lin, Yi-Hsiung; Chang, Wen-Hsin; Wu, Yang-Chang; Chang, Jan-Gowth

2012-09-01

We purified calactin from the roots of the Chinese herb Asclepias curassavica L. and analyzed its biologic effects in human leukemia cells. Our results showed that calactin treatment caused DNA damage and resulted in apoptosis. Increased phosphorylation levels of Chk2 and H2AX were observed and were reversed by the DNA damage inhibitor caffeine in calactin-treated cells. In addition, calactin treatment showed that a decrease in the expression of cell cycle regulatory proteins Cyclin B1, Cdk1, and Cdc25C was consistent with a G2/M phase arrest. Furthermore, calactin induced extracellular signal-regulated kinase (ERK) phosphorylation, activation of caspase-3, caspase-8, and caspase-9, and PARP cleavage. Pretreatment with the ERK inhibitor PD98059 significantly blocked the loss of viability in calactin-treated cells. It is indicated that calactin-induced apoptosis may occur through an ERK signaling pathway. Our data suggest that calactin is a potential anticancer compound.

Zinc protects HepG2 cells against the oxidative damage and DNA damage induced by ochratoxin A

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zheng, Juanjuan; Zhang, Yu; Xu, Wentao, E-mail: xuwentaoboy@sina.com

Oxidative stress and DNA damage are the most studied mechanisms by which ochratoxin A (OTA) induces its toxic effects, which include nephrotoxicity, hepatotoxicity, immunotoxicity and genotoxicity. Zinc, which is an essential trace element, is considered a potential antioxidant. The aim of this paper was to investigate whether zinc supplement could inhibit OTA-induced oxidative damage and DNA damage in HepG2 cells and the mechanism of inhibition. The results indicated that that exposure of OTA decreased the intracellular zinc concentration; zinc supplement significantly reduced the OTA-induced production of reactive oxygen species (ROS) and decrease in superoxide dismutase (SOD) activity but did notmore » affect the OTA-induced decrease in the mitochondrial membrane potential (Δψ{sub m}). Meanwhile, the addition of the zinc chelator N,N,N′,N′-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) strongly aggravated the OTA-induced oxidative damage. This study also demonstrated that zinc helped to maintain the integrity of DNA through the reduction of OTA-induced DNA strand breaks, 8-hydroxy-2′-deoxyguanosine (8-OHdG) formation and DNA hypomethylation. OTA increased the mRNA expression of metallothionein1-A (MT1A), metallothionein2-A (MT2A) and Cu/Zn superoxide dismutase (SOD1). Zinc supplement further enhanced the mRNA expression of MT1A and MT2A, but it had no effect on the mRNA expression of SOD1 and catalase (CAT). Zinc was for the first time proven to reduce the cytotoxicity of OTA through inhibiting the oxidative damage and DNA damage, and regulating the expression of zinc-associated genes. Thus, the addition of zinc can potentially be used to reduce the OTA toxicity of contaminated feeds. - Highlights: ► OTA decreased the intracellular zinc concentration. ► OTA induced the formation of 8-OHdG in HepG2 cells. ► It was testified for the first time that OTA induced DNA hypomethylation. ► Zinc protects against the oxidative damage and DNA damage

Laser-Induced Damage with Femtosecond Pulses

NASA Astrophysics Data System (ADS)

Kafka, Kyle R. P.

The strong electric fields of focused femtosecond laser pulses lead to non-equilibrium dynamics in materials, which, beyond a threshold intensity, causes laser-induced damage (LID). Such a strongly non-linear and non-perturbative process renders important LID observables like fluence and intensity thresholds and damage morphology (crater) extremely difficult to predict quantitatively. However, femtosecond LID carries a high degree of precision, which has been exploited in various micro/nano-machining and surface engineering applications, such as human eye surgery and super-hydrophobic surfaces. This dissertation presents an array of experimental studies which have measured the damage behavior of various materials under femtosecond irradiation. Precision experiments were performed to produce extreme spatio-temporal confinement of the femtosecond laser-solid damage interaction on monocrystalline Cu, which made possible the first successful direct-benchmarking of LID simulation with realistic damage craters. A technique was developed to produce laser-induced periodic surface structures (LIPSS) in a single pulse (typically a multi-pulse phenomenon), and was used to perform a pump-probe study which revealed asynchronous LIPSS formation on copper. Combined with 1-D calculations, this new experimental result suggests more drastic electron heating than expected. Few-cycle pulses were used to study the LID performance and morphology of commercial ultra-broadband optics, which had not been systematically studied before. With extensive surface analysis, various morphologies were observed, including LIPSS, swelling (blisters), simple craters, and even ring-shaped structures, which varied depending on the coating design, number of pulses, and air/vacuum test environment. Mechanisms leading to these morphologies are discussed, many of which are ultrafast in nature. The applied damage behavior of multi-layer dielectric mirrors was measured and compared between long pulse (150 ps

DNA damage induced by the direct effect of radiation

NASA Astrophysics Data System (ADS)

Yokoya, A.; Shikazono, N.; Fujii, K.; Urushibara, A.; Akamatsu, K.; Watanabe, R.

2008-10-01

We have studied the nature of DNA damage induced by the direct effect of radiation. The yields of single- (SSB) and double-strand breaks (DSB), base lesions and clustered damage were measured using the agarose gel electrophoresis method after exposing to various kinds of radiations to a simple model DNA molecule, fully hydrated closed-circular plasmid DNA (pUC18). The yield of SSB does not show significant dependence on linear energy transfer (LET) values. On the other hand, the yields of base lesions revealed by enzymatic probes, endonuclease III (Nth) and formamidopyrimidine DNA glycosylase (Fpg), which excise base lesions and leave a nick at the damage site, strongly depend on LET values. Soft X-ray photon (150 kVp) irradiation gives a maximum yield of the base lesions detected by the enzymatic probes as SSB and clustered damage, which is composed of one base lesion and proximate other base lesions or SSBs. The clustered damage is visualized as an enzymatically induced DSB. The yields of the enzymatically additional damages strikingly decrease with increasing levels of LET. These results suggest that in higher LET regions, the repair enzymes used as probes are compromised because of the dense damage clustering. The studies using simple plasmid DNA as a irradiation sample, however, have a technical difficulty to detect multiple SSBs in a plasmid DNA. To detect the additional SSBs induced in opposite strand of the first SSB, we have also developed a novel technique of DNA-denaturation assay. This allows us to detect multiply induced SSBs in both strand of DNA, but not induced DSB.

Role of cellular communication in the pathways of radiation-induced biological damage

NASA Astrophysics Data System (ADS)

Ballarini, Francesca; Facoetti, Angelica; Mariotti, Luca; Nano, Rosanna; Ottolenghi, Andrea

During the last decade, a large number of experimental studies on the so-called "non-targeted effects", in particular bystander effects, outlined that cellular communication plays a signifi- cant role in the pathways leading to radiation-induced biological damage. This might imply a paradigm shift in (low-dose) radiobiology, according to which one has to consider the response of groups of cells behaving like a population rather than single cells behaving as individuals. Furthermore, bystander effects, which are observed both for lethal endpoints (e.g. clonogenic inactivation and apoptosis) and for non-lethal ones (e.g. mutations and neoplastic transformation), tend to show non-linear dose responses characterized by a sharp increase followed by a plateau. This might have significant consequences in terms of low-dose risk, which is generally calculated on the basis of the "Linear No Threshold" hypothesis. Although it is known that two types of cellular communication (i.e. via gap junctions and/or molecular messengers diffusing in the extra-cellular environment, such as cytokines) play a major role, it is of utmost importance to better understand the underlying mechanisms, and how such mechanisms can be modulated by ionizing radiation. Though the "final" goal is to elucidate the in vivo scenario, in the meanwhile also in vitro studies can provide useful insights. In the present paper we will discuss key issues on the mechanisms underlying non-targeted effects and, more generally, cell communication, with focus on candidate molecular signals. Theoretical models and simulation codes can be of help in elucidating such mechanisms. In this framework, we will present a model and Monte Carlo code, under development at the University of Pavia, simulating the release, diffusion and internalization of candidate signals (typically cytokines) travelling in the extra-cellular environment, both by unirradiated (i.e., control) cells and by irradiated cells. The focus will be on the

Effects of Ionizing Radiation on Biological Molecules—Mechanisms of Damage and Emerging Methods of Detection

PubMed Central

Reisz, Julie A.; Bansal, Nidhi; Qian, Jiang; Zhao, Weiling

2014-01-01

Abstract Significance: The detrimental effects of ionizing radiation (IR) involve a highly orchestrated series of events that are amplified by endogenous signaling and culminating in oxidative damage to DNA, lipids, proteins, and many metabolites. Despite the global impact of IR, the molecular mechanisms underlying tissue damage reveal that many biomolecules are chemoselectively modified by IR. Recent Advances: The development of high-throughput “omics” technologies for mapping DNA and protein modifications have revolutionized the study of IR effects on biological systems. Studies in cells, tissues, and biological fluids are used to identify molecular features or biomarkers of IR exposure and response and the molecular mechanisms that regulate their expression or synthesis. Critical Issues: In this review, chemical mechanisms are described for IR-induced modifications of biomolecules along with methods for their detection. Included with the detection methods are crucial experimental considerations and caveats for their use. Additional factors critical to the cellular response to radiation, including alterations in protein expression, metabolomics, and epigenetic factors, are also discussed. Future Directions: Throughout the review, the synergy of combined “omics” technologies such as genomics and epigenomics, proteomics, and metabolomics is highlighted. These are anticipated to lead to new hypotheses to understand IR effects on biological systems and improve IR-based therapies. Antioxid. Redox Signal. 21: 260–292. PMID:24382094

The effect of 2-[(aminopropyl)amino] ethanethiol on fission-neutron-induced DNA damage and repair.

PubMed Central

Grdina, D. J.; Sigdestad, C. P.; Dale, P. J.; Perrin, J. M.

1989-01-01

The effect(s) of the radioprotector 2-[(aminopropyl)amino] ethanethiol (WR 1065) on fission-neutron-induced DNA damage and repair in V79 Chinese hamster cells was determined by using a neutral filter elution procedure (pH 7.2). When required, WR1065, at a final working concentration of 4 mM, was added to the culture medium, either 30 min before and during irradiation with fission spectrum neutrons (beam energy of 0.85 MeV) from the JANUS research reactor, or for selected intervals of time following exposure. The frequency of neutron-induced DNA strand breaks as measured by neutral elution as a function of dose equalled that observed for 60Co gamma-ray-induced damage (relative biological effectiveness of one). In contrast to the protective effect exhibited by WR1065 in reducing 60Co-induced DNA damage, WR1065 was ineffective in reducing or protecting against induction of DNA strand breaks by JANUS neutrons. The kinetics of DNA double-strand rejoining were measured following neutron irradiation. In the absence of WR1065, considerable DNA degradation by cellular enzymes was observed. This process was inhibited when WR1065 was present. These results indicate that, under the conditions used, the quality (i.e. nature), rather than quantity, of DNA lesions (measured by neutral elution) formed by neutrons was significantly different from that formed by gamma-rays. PMID:2667608

Opportunities for nutritional amelioration of radiation-induced cellular damage

NASA Technical Reports Server (NTRS)

Turner, Nancy D.; Braby, Leslie A.; Ford, John; Lupton, Joanne R.

2002-01-01

The closed environment and limited evasive capabilities inherent in space flight cause astronauts to be exposed to many potential harmful agents (chemical contaminants in the environment and cosmic radiation exposure). Current power systems used to achieve space flight are prohibitively expensive for supporting the weight requirements to fully shield astronauts from cosmic radiation. Therefore, radiation poses a major, currently unresolvable risk for astronauts, especially for long-duration space flights. The major detrimental radiation effects that are of primary concern for long-duration space flights are damage to the lens of the eye, damage to the immune system, damage to the central nervous system, and cancer. In addition to the direct damage to biological molecules in cells, radiation exposure induces oxidative damage. Many natural antioxidants, whether consumed before or after radiation exposure, are able to confer some level of radioprotection. In addition to achieving beneficial effects from long-known antioxidants such as vitamins E and C and folic acid, some protection is conferred by several recently discovered antioxidant molecules, such as flavonoids, epigallocatechin, and other polyphenols. Somewhat counterintuitive is the protection provided by diets containing elevated levels of omega-3 polyunsaturated fatty acids, considering they are thought to be prone to peroxidation. Even with the information we have at our disposal, it will be difficult to predict the types of dietary modifications that can best reduce the risk of radiation exposure to astronauts, those living on Earth, or those enduring diagnostic or therapeutic radiation exposure. Much more work must be done in humans, whether on Earth or, preferably, in space, before we are able to make concrete recommendations.

DNA damage induced by ascorbate in the presence of Cu2+.

PubMed

Kobayashi, S; Ueda, K; Morita, J; Sakai, H; Komano, T

1988-01-25

DNA damage induced by ascorbate in the presence of Cu2+ was investigated by use of bacteriophage phi X174 double-stranded supercoiled DNA and linear restriction fragments as substrates. Single-strand cleavage was induced when supercoiled DNA was incubated with 5 microM-10 mM ascorbate and 50 microM Cu2+ at 37 degrees C for 10 min. The induced DNA damage was analyzed by sequencing of fragments singly labeled at their 5'- or 3'-end. DNA was cleaved directly and almost uniformly at every nucleotide by ascorbate and Cu2+. Piperidine treatment after the reaction showed that ascorbate and Cu2+ induced another kind of DNA damage different from the direct cleavage. The damage proceeded to DNA cleavage by piperidine treatment and was sequence-specific rather than random. These results indicate that ascorbate induces two classes of DNA damage in the presence of Cu2+, one being direct strand cleavage, probably via damage to the DNA backbone, and the other being a base modification labile to alkali treatment. These two classes of DNA damage were inhibited by potassium iodide, catalase and metal chelaters, suggesting the involvement of radicals generated from ascorbate hydroperoxide.

An extended sequence specificity for UV-induced DNA damage.

PubMed

Chung, Long H; Murray, Vincent

2018-01-01

The sequence specificity of UV-induced DNA damage was determined with a higher precision and accuracy than previously reported. UV light induces two major damage adducts: cyclobutane pyrimidine dimers (CPDs) and pyrimidine(6-4)pyrimidone photoproducts (6-4PPs). Employing capillary electrophoresis with laser-induced fluorescence and taking advantages of the distinct properties of the CPDs and 6-4PPs, we studied the sequence specificity of UV-induced DNA damage in a purified DNA sequence using two approaches: end-labelling and a polymerase stop/linear amplification assay. A mitochondrial DNA sequence that contained a random nucleotide composition was employed as the target DNA sequence. With previous methodology, the UV sequence specificity was determined at a dinucleotide or trinucleotide level; however, in this paper, we have extended the UV sequence specificity to a hexanucleotide level. With the end-labelling technique (for 6-4PPs), the consensus sequence was found to be 5'-GCTC*AC (where C* is the breakage site); while with the linear amplification procedure, it was 5'-TCTT*AC. With end-labelling, the dinucleotide frequency of occurrence was highest for 5'-TC*, 5'-TT* and 5'-CC*; whereas it was 5'-TT* for linear amplification. The influence of neighbouring nucleotides on the degree of UV-induced DNA damage was also examined. The core sequences consisted of pyrimidine nucleotides 5'-CTC* and 5'-CTT* while an A at position "1" and C at position "2" enhanced UV-induced DNA damage. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

Shock-induced damage in rocks: Application to impact cratering

NASA Astrophysics Data System (ADS)

Ai, Huirong

Shock-induced damage beneath impact craters is studied in this work. Two representative terrestrial rocks, San Marcos granite and Bedford limestone, are chosen as test target. Impacts into the rock targets with different combinations of projectile material, size, impact angle, and impact velocity are carried out at cm scale in the laboratory. Shock-induced damage and fracturing would cause large-scale compressional wave velocity reduction in the recovered target beneath the impact crater. The shock-induced damage is measured by mapping the compressional wave velocity reduction in the recovered target. A cm scale nondestructive tomography technique is developed for this purpose. This technique is proved to be effective in mapping the damage in San Marcos granite, and the inverted velocity profile is in very good agreement with the result from dicing method and cut open directly. Both compressional velocity and attenuation are measured in three orthogonal directions on cubes prepared from one granite target impacted by a lead bullet at 1200 m/s. Anisotropy is observed from both results, but the attenuation seems to be a more useful parameter than acoustic velocity in studying orientation of cracks. Our experiments indicate that the shock-induced damage is a function of impact conditions including projectile type and size, impact velocity, and target properties. Combined with other crater phenomena such as crater diameter, depth, ejecta, etc., shock-induced damage would be used as an important yet not well recognized constraint for impact history. The shock-induced damage is also calculated numerically to be compared with the experiments for a few representative shots. The Johnson-Holmquist strength and failure model, initially developed for ceramics, is applied to geological materials. Strength is a complicated function of pressure, strain, strain rate, and damage. The JH model, coupled with a crack softening model, is used to describe both the inelastic response of

A tissue phantom for visualization and measurement of ultrasound-induced cavitation damage.

PubMed

Maxwell, Adam D; Wang, Tzu-Yin; Yuan, Lingqian; Duryea, Alexander P; Xu, Zhen; Cain, Charles A

2010-12-01

Many ultrasound studies involve the use of tissue-mimicking materials to research phenomena in vitro and predict in vivo bioeffects. We have developed a tissue phantom to study cavitation-induced damage to tissue. The phantom consists of red blood cells suspended in an agarose hydrogel. The acoustic and mechanical properties of the gel phantom were found to be similar to soft tissue properties. The phantom's response to cavitation was evaluated using histotripsy. Histotripsy causes breakdown of tissue structures by the generation of controlled cavitation using short, focused, high-intensity ultrasound pulses. Histotripsy lesions were generated in the phantom and kidney tissue using a spherically focused 1-MHz transducer generating 15 cycle pulses, at a pulse repetition frequency of 100 Hz with a peak negative pressure of 14 MPa. Damage appeared clearly as increased optical transparency of the phantom due to rupture of individual red blood cells. The morphology of lesions generated in the phantom was very similar to that generated in kidney tissue at both macroscopic and cellular levels. Additionally, lesions in the phantom could be visualized as hypoechoic regions on a B-mode ultrasound image, similar to histotripsy lesions in tissue. High-speed imaging of the optically transparent phantom was used to show that damage coincides with the presence of cavitation. These results indicate that the phantom can accurately mimic the response of soft tissue to cavitation and provide a useful tool for studying damage induced by acoustic cavitation. Copyright © 2010 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Damage-free vibrational spectroscopy of biological materials in the electron microscope

PubMed Central

Rez, Peter; Aoki, Toshihiro; March, Katia; Gur, Dvir; Krivanek, Ondrej L.; Dellby, Niklas; Lovejoy, Tracy C.; Wolf, Sharon G.; Cohen, Hagai

2016-01-01

Vibrational spectroscopy in the electron microscope would be transformative in the study of biological samples, provided that radiation damage could be prevented. However, electron beams typically create high-energy excitations that severely accelerate sample degradation. Here this major difficulty is overcome using an ‘aloof' electron beam, positioned tens of nanometres away from the sample: high-energy excitations are suppressed, while vibrational modes of energies <1 eV can be ‘safely' investigated. To demonstrate the potential of aloof spectroscopy, we record electron energy loss spectra from biogenic guanine crystals in their native state, resolving their characteristic C–H, N–H and C=O vibrational signatures with no observable radiation damage. The technique opens up the possibility of non-damaging compositional analyses of organic functional groups, including non-crystalline biological materials, at a spatial resolution of ∼10 nm, simultaneously combined with imaging in the electron microscope. PMID:26961578

Damage-free vibrational spectroscopy of biological materials in the electron microscope.

PubMed

Rez, Peter; Aoki, Toshihiro; March, Katia; Gur, Dvir; Krivanek, Ondrej L; Dellby, Niklas; Lovejoy, Tracy C; Wolf, Sharon G; Cohen, Hagai

2016-03-10

Vibrational spectroscopy in the electron microscope would be transformative in the study of biological samples, provided that radiation damage could be prevented. However, electron beams typically create high-energy excitations that severely accelerate sample degradation. Here this major difficulty is overcome using an 'aloof' electron beam, positioned tens of nanometres away from the sample: high-energy excitations are suppressed, while vibrational modes of energies <1 eV can be 'safely' investigated. To demonstrate the potential of aloof spectroscopy, we record electron energy loss spectra from biogenic guanine crystals in their native state, resolving their characteristic C-H, N-H and C=O vibrational signatures with no observable radiation damage. The technique opens up the possibility of non-damaging compositional analyses of organic functional groups, including non-crystalline biological materials, at a spatial resolution of ∼10 nm, simultaneously combined with imaging in the electron microscope.

Subsurface defects of fused silica optics and laser induced damage at 351 nm.

PubMed

Hongjie, Liu; Jin, Huang; Fengrui, Wang; Xinda, Zhou; Xin, Ye; Xiaoyan, Zhou; Laixi, Sun; Xiaodong, Jiang; Zhan, Sui; Wanguo, Zheng

2013-05-20

Many kinds of subsurface defects are always present together in the subsurface of fused silica optics. It is imperfect that only one kind of defects is isolated to investigate its impact on laser damage. Therefore it is necessary to investigate the impact of subsurface defects on laser induced damage of fused silica optics with a comprehensive vision. In this work, we choose the fused silica samples manufactured by different vendors to characterize subsurface defects and measure laser induced damage. Contamination defects, subsurface damage (SSD), optical-thermal absorption and hardness of fused silica surface are characterized with time-of-flight secondary ion mass spectrometry (TOF-SIMS), fluorescence microscopy, photo-thermal common-path interferometer and fully automatic micro-hardness tester respectively. Laser induced damage threshold and damage density are measured by 351 nm nanosecond pulse laser. The correlations existing between defects and laser induced damage are analyzed. The results show that Cerium element and SSD both have a good correlation with laser-induced damage thresholds and damage density. Research results evaluate process technology of fused silica optics in China at present. Furthermore, the results can provide technique support for improving laser induced damage performance of fused silica.

Characterization of laser induced damage of HR coatings with picosecond pulses

NASA Astrophysics Data System (ADS)

Li, Cheng; Zhao, Yuan'an; Cui, Yun; Wang, Yueliang; Peng, Xiaocong; Shan, Chong; Zhu, Meiping; Wang, Jianguo; Shao, Jianda

2017-11-01

The effect of protective layer on the picosecond laser-induced damage behaviors of HfO2/SiO2 high-reflective (HR) coatings are explored. Two kinds of 1064nm HR coatings with and without protective layer are deposited by electron beam evaporation. Laser-induced damage tests are conducted with 1064nm, 30ps S-polarized and P-polarized pulses with different angle of incidence (AOI) to make the electric fields intensity in the HR coatings discrepantly. Damage morphology and cross section of damage sites were characterized by scanning electron microscope (SEM) and focused ion beam (FIB), respectively. It is found that SiO2 protective layer have a certain degree of improvement on laser induced damage threshold (LIDT) for every AOIs. The onset damage initiated very near to the Max peak of e-field, after which forms ripple-like pits. The damage morphology presents as layer delamination at high fluence. The Laser damage resistance is correspond with the maximum E-intensity in the coating stacks.

DNA damage in cells exhibiting radiation-induced genomic instability

DOE PAGES

Keszenman, Deborah J.; Kolodiuk, Lucia; Baulch, Janet E.

2015-02-22

Cells exhibiting radiation induced genomic instability exhibit varied spectra of genetic and chromosomal aberrations. Even so, oxidative stress remains a common theme in the initiation and/or perpetuation of this phenomenon. Isolated oxidatively modified bases, abasic sites, DNA single strand breaks and clustered DNA damage are induced in normal mammalian cultured cells and tissues due to endogenous reactive oxygen species generated during normal cellular metabolism in an aerobic environment. While sparse DNA damage may be easily repaired, clustered DNA damage may lead to persistent cytotoxic or mutagenic events that can lead to genomic instability. In this study, we tested the hypothesismore » that DNA damage signatures characterised by altered levels of endogenous, potentially mutagenic, types of DNA damage and chromosomal breakage are related to radiation-induced genomic instability and persistent oxidative stress phenotypes observed in the chromosomally unstable progeny of irradiated cells. The measurement of oxypurine, oxypyrimidine and abasic site endogenous DNA damage showed differences in non-double-strand breaks (DSB) clusters among the three of the four unstable clones evaluated as compared to genomically stable clones and the parental cell line. These three unstable clones also had increased levels of DSB clusters. The results of this study demonstrate that each unstable cell line has a unique spectrum of persistent damage and lead us to speculate that alterations in DNA damage signaling and repair may be related to the perpetuation of genomic instability.« less

Balance between senescence and apoptosis is regulated by telomere damage-induced association between p16 and caspase-3.

PubMed

Panneer Selvam, Shanmugam; Roth, Braden M; Nganga, Rose; Kim, Jisun; Cooley, Marion A; Helke, Kristi L; Smith, Charles D; Ogretmen, Besim

2018-05-10

Telomerase activation protects cells from telomere damage by delaying senescence and inducing cell immortalization, whereas telomerase inhibition mediates rapid senescence or apoptosis. However, the cellular mechanisms that determine telomere damage-dependent senescence versus apoptosis induction are largely unknown. Here, we demonstrate that telomerase instability mediated by silencing of sphingosine kinase 2 (SPHK2) and sphingosine 1-phosphate (S1P), which binds and stabilizes telomerase, induces telomere damage-dependent caspase-3 activation and apoptosis, but not senescence, in p16-deficient lung cancer cells or tumors. These outcomes were prevented by knockdown of a tumor-suppressor protein, transcription factor 21 (TCF21), or by ectopic expression of WT human telomerase reverse transcriptase (hTERT), but not mutant hTERT with altered S1P binding. Interestingly, SphK2-deficient mice exhibited accelerated aging and telomerase instability that increased telomere damage and senescence via p16 activation especially in testes tissues, but not in apoptosis. Moreover, p16 silencing in SphK2-/- mouse embryonic fibroblasts activated caspase-3 and apoptosis without inducing senescence. Further, ectopic WT p16 expression in p16-deficient A549 lung cancer cells prevented TCF21 and caspase-3 activation, and resulted in senescence in response to SphK2/S1P inhibition and telomere damage. Mechanistically, a p16 mutant with impaired [MS2] caspase-3 association did not prevent telomere damage-induced apoptosis, indicating that an association between p16 and caspase-3 proteins forces senescence induction by inhibiting caspase-3 activation and apoptosis.[MS3]  These results suggest that p16 plays a direct role in telomere damage-dependent senescence by limiting apoptosis via binding to caspase-3, revealing a direct link between telomere damage-dependent senescence and apoptosis with regards to aging and cancer. Published under license by The American Society for Biochemistry

The Biological Effectiveness of Accelerated Particles for the Induction of Chromosome Damage: Track Structure Effects and Cytogenetic Signatures of High-LET Exposure

NASA Technical Reports Server (NTRS)

George, K.; Hada, M.; Chappell, L.; Cucinotta, F. A.

2012-01-01

Track structure models predict that at a fixed value of LET, particles with lower charge number, Z will have a higher biological effectiveness compared to particles with a higher Z. In this report we investigated how track structure effects induction of chromosomal aberration in human cells. Human lymphocytes were irradiated in vitro with various energies of accelerated iron, silicon, neon, or titanium ions and chromosome damage was assessed in using three color FISH chromosome painting in chemically induced PCC samples collected a first cell division post irradiation. The LET values for these ions ranged from 30 to 195 keV/micrometers. Of the particles studied, Neon ions have the highest biological effectiveness for induction of total chromosome damage, which is consistent with track structure model predictions. For complex-type exchanges 64 MeV/ u Neon and 450 MeV/u Iron were equally effective and induced the most complex damage. In addition we present data on chromosomes exchanges induced by six different energies of protons (5 MeV/u to 2.5 GeV/u). The linear dose response term was similar for all energies of protons suggesting that the effect of the higher LET at low proton energies is balanced by the production of nuclear secondaries from the high energy protons. All energies of protons have a much higher percentage of complex-type chromosome exchanges than gamma rays, signifying a cytogenetic signature for proton exposures.

Cerium oxide nanoparticles, combining antioxidant and UV shielding properties, prevent UV-induced cell damage and mutagenesis

NASA Astrophysics Data System (ADS)

Caputo, Fanny; de Nicola, Milena; Sienkiewicz, Andrzej; Giovanetti, Anna; Bejarano, Ignacio; Licoccia, Silvia; Traversa, Enrico; Ghibelli, Lina

2015-09-01

Efficient inorganic UV shields, mostly based on refracting TiO2 particles, have dramatically changed the sun exposure habits. Unfortunately, health concerns have emerged from the pro-oxidant photocatalytic effect of UV-irradiated TiO2, which mediates toxic effects on cells. Therefore, improvements in cosmetic solar shield technology are a strong priority. CeO2 nanoparticles are not only UV refractors but also potent biological antioxidants due to the surface 3+/4+ valency switch, which confers anti-inflammatory, anti-ageing and therapeutic properties. Herein, UV irradiation protocols were set up, allowing selective study of the extra-shielding effects of CeO2vs. TiO2 nanoparticles on reporter cells. TiO2 irradiated with UV (especially UVA) exerted strong photocatalytic effects, superimposing their pro-oxidant, cell-damaging and mutagenic action when induced by UV, thereby worsening the UV toxicity. On the contrary, irradiated CeO2 nanoparticles, via their Ce3+/Ce4+ redox couple, exerted impressive protection on UV-treated cells, by buffering oxidation, preserving viability and proliferation, reducing DNA damage and accelerating repair; strikingly, they almost eliminated mutagenesis, thus acting as an important tool to prevent skin cancer. Interestingly, CeO2 nanoparticles also protect cells from the damage induced by irradiated TiO2, suggesting that these two particles may also complement their effects in solar lotions. CeO2 nanoparticles, which intrinsically couple UV shielding with biological and genetic protection, appear to be ideal candidates for next-generation sun shields.

Damage-free vibrational spectroscopy of biological materials in the electron microscope

DOE PAGES

Rez, Peter; Aoki, Toshihiro; March, Katia; ...

2016-03-10

Vibrational spectroscopy in the electron microscope would be transformative in the study of biological samples, provided that radiation damage could be prevented. However, electron beams typically create high-energy excitations that severely accelerate sample degradation. Here this major difficulty is overcome using an ‘aloof’ electron beam, positioned tens of nanometres away from the sample: high-energy excitations are suppressed, while vibrational modes of energies o1 eV can be ‘safely’ investigated. To demonstrate the potential of aloof spectroscopy, we record electron energy loss spectra from biogenic guanine crystals in their native state, resolving their characteristic C–H, N–H and C=O vibrational signatures with nomore » observable radiation damage. Furthermore, the technique opens up the possibility of non-damaging compositional analyses of organic functional groups, including non-crystalline biological materials, at a spatial resolution of ~10nm, simultaneously combined with imaging in the electron microscope.« less

Damage-free vibrational spectroscopy of biological materials in the electron microscope

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rez, Peter; Aoki, Toshihiro; March, Katia

Vibrational spectroscopy in the electron microscope would be transformative in the study of biological samples, provided that radiation damage could be prevented. However, electron beams typically create high-energy excitations that severely accelerate sample degradation. Here this major difficulty is overcome using an ‘aloof’ electron beam, positioned tens of nanometres away from the sample: high-energy excitations are suppressed, while vibrational modes of energies o1 eV can be ‘safely’ investigated. To demonstrate the potential of aloof spectroscopy, we record electron energy loss spectra from biogenic guanine crystals in their native state, resolving their characteristic C–H, N–H and C=O vibrational signatures with nomore » observable radiation damage. Furthermore, the technique opens up the possibility of non-damaging compositional analyses of organic functional groups, including non-crystalline biological materials, at a spatial resolution of ~10nm, simultaneously combined with imaging in the electron microscope.« less

Low-concentration BPAF- and BPF-induced cell biological effects are mediated by ROS in MCF-7 breast cancer cells.

PubMed

Lei, Bingli; Sun, Su; Xu, Jie; Feng, Chenglian; Yu, Yingxin; Xu, Gang; Wu, Minghong; Peng, Wei

2018-02-01

Reactive oxygen species (ROS) induced by bisphenol A (BPA) have been implicated in cellular oxidative damage and carcinogenesis. It is not known whether the potential alternatives of BPA, bisphenol AF (BPAF), and bisphenol F (BPF) can also induce ROS involved in mediating biological responses. This study evaluated the toxicity of BPAF and BPF on cell proliferation, DNA damage, intracellular calcium homeostasis, and ROS generation in MCF-7 human breast cancer cells. The results showed that BPAF at 0.001-1 μM and BPF at 0.01-1 μM significantly increased cell viability and at 25 and 50 μM, both compounds decreased cell viability. At 0.01-10 μM, both BPAF and BPF increased DNA damage and significantly elevated ROS and intracellular Ca 2+ levels in MCF-7 cells. These biological effects were attenuated by the ROS scavenger N-acetylcysteine (NAC), indicating that ROS played a key role in the observed biological effects of BPAF and BPF on MCF-7 cells. These findings can deepen our understanding on the toxicity of BPAF and BPF, and provide basis data to further evaluate the potential health harm and establish environmental standard of BPAF and BPF.

Parvovirus infection-induced DNA damage response

PubMed Central

Luo, Yong; Qiu, Jianming

2014-01-01

Parvoviruses are a group of small DNA viruses with ssDNA genomes flanked by two inverted terminal structures. Due to a limited genetic resource they require host cellular factors and sometimes a helper virus for efficient viral replication. Recent studies have shown that parvoviruses interact with the DNA damage machinery, which has a significant impact on the life cycle of the virus as well as the fate of infected cells. In addition, due to special DNA structures of the viral genomes, parvoviruses are useful tools for the study of the molecular mechanisms underlying viral infection-induced DNA damage response (DDR). This review aims to summarize recent advances in parvovirus-induced DDR, with a focus on the diverse DDR pathways triggered by different parvoviruses and the consequences of DDR on the viral life cycle as well as the fate of infected cells. PMID:25429305

Impact of mechanical stress induced in silica vacuum windows on laser-induced damage.

PubMed

Gingreau, Clémence; Lanternier, Thomas; Lamaignère, Laurent; Donval, Thierry; Courchinoux, Roger; Leymarie, Christophe; Néauport, Jérôme

2018-04-15

At the interface between vacuum and air, optical windows must keep their optical properties, despite being subjected to mechanical stress. In this Letter, we investigate the impact of such stress on the laser-induced damage of fused silica windows at the wavelength of 351 nm in the nanosecond regime. Different stress values, from 1 to 30 MPa, both tensile and compressive, were applied. No effect of the stress on the laser-induced damage was evidenced.

The effects of metal ions on the DNA damage induced by hydrogen peroxide.

PubMed

Kobayashi, S; Ueda, K; Komano, T

1990-01-01

The effects of metal ions on DNA damage induced by hydrogen peroxide were investigated using two methods, agarose-gel electrophoretic analysis of supercoiled DNA and sequencing-gel analysis of single end-labeled DNA fragments of defined sequences. Hydrogen peroxide induced DNA damage when iron or copper ion was present. At least two classes of DNA damage were induced, one being direct DNA-strand cleavage, and the other being base modification labile to hot piperidine. The investigation of the damaged sites and the inhibitory effects of radical scavengers revealed that hydroxyl radical was the species which attacked DNA in the reaction of H2O2/Fe(II). On the other hand, two types of DNA damage were induced by H2O2/Cu(II). Type I damage was predominant and inhibited by potassium iodide, but type II was not. The sites of the base-modification induced by type I damage were similar to those by lipid peroxidation products and by ascorbate in the presence of Cu(II), suggesting the involvement of radical species other than free hydroxyl radical in the damaging reactions.

Solar ultraviolet radiation induces biological alterations in human skin in vitro: relevance of a well-balanced UVA/UVB protection.

PubMed

Bernerd, Francoise; Marionnet, Claire; Duval, Christine

2012-06-01

Cutaneous damages such as sunburn, pigmentation, and photoaging are known to be induced by acute as well as repetitive sun exposure. Not only for basic research, but also for the design of the most efficient photoprotection, it is crucial to understand and identify the early biological events occurring after ultraviolet (UV) exposure. Reconstructed human skin models provide excellent and reliable in vitro tools to study the UV-induced alterations of the different skin cell types, keratinocytes, fibroblasts, and melanocytes in a dose- and time-dependent manner. Using different in vitro human skin models, the effects of UV light (UVB and UVA) were investigated. UVB-induced damages are essentially epidermal, with the typical sunburn cells and DNA lesions, whereas UVA radiation-induced damages are mostly located within the dermal compartment. Pigmentation can also be obtained after solar simulated radiation exposure of pigmented reconstructed skin model. Those models are also highly adequate to assess the potential of sunscreens to protect the skin from UV-associated damage, sunburn reaction, photoaging, and pigmentation. The results showed that an effective photoprotection is provided by broad-spectrum sunscreens with a potent absorption in both UVB and UVA ranges.

The control of iron-induced oxidative damage in isolated rat-liver mitochondria by respiration state and ascorbate.

PubMed

Burkitt, M J; Gilbert, B C

1989-01-01

The reaction of iron (II) with H2O2 is believed to generate highly reactive species (e.g. .OH) capable of initiating biological damage. This study investigates the possibility that the severity of oxidative damage induced by iron in hepatic mitochondria is determined by the level of mitochondrial-H2O2 generation, which is believed to be particularly prominent in state-4 respiration. Iron-induced damage is found to be greater in state-4 than in state-3 respiration. Experiments using uncoupling agents and Ca++ to mimic state-3 conditions indicate that this effect reflects differences in the steady-state oxidation-level of the electron carriers of the respiratory chain (and hence the level of H2O2-generation), rather than changes in redox potential or transportation of the metal-ion. Evidence is also presented for a mechanism in which Fe(II) and H2O2 react inside the mitochondrial matrix. Ascorbate (vitamin C) is shown to be pro-oxidant in this system, except when present at very high concentration when it becomes antioxidant in nature.

Biological effectiveness of accelerated particles for the induction of chromosome damage: track structure effects.

PubMed

George, Kerry A; Hada, Megumi; Chappell, Lori; Cucinotta, Francis A

2013-07-01

We have investigated how radiation quality affects the induction of chromosomal aberrations in human cells. Human lymphocytes were irradiated in vitro with various energies of accelerated high charge and energy (HZE) particles including oxygen, neon, silicon, titanium and iron. Chromosome damage was assessed using three-color FISH chromosome painting in chemically induced premature chromosome condensation samples collected at first cell division after irradiation. The LET values for these particles ranged from 30 to 195 keV/μm, and their energies ranged from about 55 MeV/u to more than 1,000 MeV/u. The 89 and 142 MeV/u neon particles produced the most simple-type reciprocal exchanges per unit dose. For complex-type exchanges, 64 MeV/u neon and 450 MeV/u iron were equally effective and induced the greatest amount of complex damage. Track structure models predict that at a fixed value of LET, particles with lower charge number (Z) will have a higher biological effectiveness compared to particles with a higher Z, and that a saturation cross section will be observed for different radiation qualities. Our results are consistent with model expectations within the limitation of experimental error, and provide the most extensive data that have been reported on the radiation quality dependences of chromosomal aberrations. © 2013 by Radiation Research Society

Long-term biological effects induced by ionizing radiation--implications for dose mediated risk.

PubMed

Miron, S D; Astărăstoae, V

2014-01-01

Ionizing radiations are considered to be risk agents that are responsible for the effects on interaction with living matter. The occurring biological effects are due to various factors such as: dose, type of radiation, exposure time, type of biological tissue, health condition and the age of the person exposed. The mechanisms involved in the direct modifications of nuclear DNA and mitochondrial DNA are reviewed. Classical target theory of energy deposition in the nucleus that causes DNA damages, in particular DNA double-strand breaks and that explanation of the biological consequences of ionizing radiation exposure is a paradigm in radiobiology. Recent experimental evidences have demonstrated the existence of a molecular mechanism that explains the non-targeted effects of ionizing radiation exposure. Among these novel data, genomic instability and a variety of bystander effects are discussed here. Those bystander effects of ionizing radiation are fulfilled by cellular communication systems that give rise to non-targeted effects in the neighboring non irradiated cells. This paper provides also a commentary on the synergistic effects induced by the co-exposures to ionizing radiation and various physical agents such as electromagnetic fields and the co-exposures to ionizing radiation and chemical environmental contaminants such as metals. The biological effects of multiple stressors on genomic instability and bystander effects are also discussed. Moreover, a brief presentation of the methods used to characterize cyto- and genotoxic damages is offered.

Hemorrhage-induced intestinal damage is complement independent in Helicobacter-hepaticus infected mice

PubMed Central

Hylton, Diana J.; Phillips, Lauren M.; Hoffman, Sara M.; Fleming, Sherry D.

2010-01-01

With over half of the world population infected, Helicobacter infection is an important public health issue associated with gastrointestinal cancers and inflammatory bowel disease. Animal studies indicate that complement and oxidative stress play a role in Helicobacter infections. Hemorrhage induces tissue damage which is attenuated by blockade of either complement activation or oxidative stress products. Therefore, we hypothesized that chronic Helicobacter hepaticus infection would modulate hemorrhage-induced intestinal damage and inflammation. To test this hypothesis, we examined hemorrhage-induced jejunal damage and inflammation in uninfected and H. hepaticus infected mice. H. hepaticus infection increased hemorrhage-induced mid-jejunal mucosal damage despite attenuating complement activation. In addition, infection alone increased chemokine secretion, changing the hemorrhage-induced neutrophil infiltration to a macrophage-mediated inflammatory response. The hemorrhage-induced macrophage infiltration correlated with increased secretion of tumor necrosis factor-α (TNF-α3) and nitric oxide (NO) in the infected mice. Together these data indicate that Helicobacter infection modulates the mechanism of hemorrhage-induced intestinal damage and inflammation from a complement-mediated response to a macrophage response with elevated TNF-α and NO. These data indicate that chronic, low level infections change the response to trauma and should be considered when designing and administering therapeutics. PMID:20220569

Molecular and sensory mechanisms to mitigate sunlight-induced DNA damage in treefrog tadpoles.

PubMed

Schuch, André P; Lipinski, Victor M; Santos, Mauricio B; Santos, Caroline P; Jardim, Sinara S; Cechin, Sonia Z; Loreto, Elgion L S

2015-10-01

The increased incidence of solar ultraviolet B (UVB) radiation has been proposed as an environmental stressor, which may help to explain the enigmatic decline of amphibian populations worldwide. Despite growing knowledge regarding the UV-induced biological effects in several amphibian models, little is known about the efficacy of DNA repair pathways. In addition, little attention has been given to the interplay between these molecular mechanisms with other physiological strategies that avoid the damage induced by sunlight. Here, DNA lesions induced by environmental doses of solar UVB and UVA radiation were detected in genomic DNA samples of treefrog tadpoles (Hypsiboas pulchellus) and their DNA repair activity was evaluated. These data were complemented by monitoring the induction of apoptosis in blood cells and tadpole survival. Furthermore, the tadpoles' ability to perceive and escape from UV wavelengths was evaluated as an additional strategy of photoprotection. The results show that tadpoles are very sensitive to UVB light, which could be explained by the slow DNA repair rates for both cyclobutane pyrimidine dimers (CPDs) and pyrimidine (6,4) pyrimidone photoproducts (6,4PPs). However, they were resistant to UVA, probably as a result of the activation of photolyases during UVA irradiation. Surprisingly, a sensory mechanism that triggers their escape from UVB and UVA light avoids the generation of DNA damage and helps to maintain the genomic integrity. This work demonstrates the genotoxic impact of both UVB and UVA radiation on tadpoles and emphasizes the importance of the interplay between molecular and sensory mechanisms to minimize the damage caused by sunlight. © 2015. Published by The Company of Biologists Ltd.

DNA damage induces nuclear actin filament assembly by Formin -2 and Spire-½ that promotes efficient DNA repair. [corrected].

PubMed

Belin, Brittany J; Lee, Terri; Mullins, R Dyche

2015-08-19

Actin filaments assemble inside the nucleus in response to multiple cellular perturbations, including heat shock, protein misfolding, integrin engagement, and serum stimulation. We find that DNA damage also generates nuclear actin filaments-detectable by phalloidin and live-cell actin probes-with three characteristic morphologies: (i) long, nucleoplasmic filaments; (ii) short, nucleolus-associated filaments; and (iii) dense, nucleoplasmic clusters. This DNA damage-induced nuclear actin assembly requires two biologically and physically linked nucleation factors: Formin-2 and Spire-1/Spire-2. Formin-2 accumulates in the nucleus after DNA damage, and depletion of either Formin-2 or actin's nuclear import factor, importin-9, increases the number of DNA double-strand breaks (DSBs), linking nuclear actin filaments to efficient DSB clearance. Nuclear actin filaments are also required for nuclear oxidation induced by acute genotoxic stress. Our results reveal a previously unknown role for nuclear actin filaments in DNA repair and identify the molecular mechanisms creating these nuclear filaments.

Ultrasound-induced cavitation damage to external epithelia of fish skin.

PubMed

Frenkel, V; Kimmel, E; Iger, Y

1999-10-01

Transmission electron microscopy was used to show the effects of therapeutic ultrasound (< or = 1.0 W/cm2, 1 MHz) on the external epithelia of fish skin. Exposures of up to 90 s produced damage to 5 to 6 of the outermost layers. Negligible temperature elevations and lack of damage observed when using degassed water indicated that the effects were due to cavitation. The minimal intensity was determined for inducing cellular damage, where the extent and depth of damage to the tissues was correlated to the exposure duration. The results may be interpreted as a damage front, advancing slowly from the outer cells inward, presumably in association with the slow replacement of the perforated cell contents with the surrounding water. This study illustrates that a controlled level of microdamage may be induced to the outer layers of the tissues.

[The role of free radicals in the UV-induced skin damage. Photo-aging].

PubMed

Emri, Gabriella; Horkay, Irén; Remenyik, Eva

2006-04-23

The natural (intrinsic) ageing of the skin is enhanced by environmental factors (extrinsic ageing). One of the most important exogenous factors is the solar UV exposure, which results in photo-aging. Besides this, epidemiological and experimental data show a rapid increase in the incidence of human skin cancers, which is also in relation to the increased sunlight exposure of the skin. In the background of these processes there are cell biological effects, photochemical reactions, membrane receptor changes, lipid- and protein modifications, DNA-damage induced by UV. The qualities and quantities of them are wavelength dependent. The UVB photons are absorbed mostly by the DNA of the epidermal keratinocytes, therefore this spectrum is more relevant for photocarcinogenesis. The effect of UVA-irradiation is mainly manifested in the induction of free radicals, which have not only DNA-damaging, but also immunomodulating effect, which also can influence on tumour development. Furthermore, the free radicals cause dermal connective tissue damage as well via activating transcription factors, inducing matrix metalloproteinases, diminishing the procollagen I and fibrillin-1 synthesis. These processes are augmented by mitochondrial DNA mutations, protein oxidation, apoptosis induction. Therefore the enzymes neutralising free radicals and antioxidant molecules, respectively, have an important role in the defence mechanisms. In the therapy of photo-aging the local retinoids lived up to expectations, but the clinical effectiveness of antioxidant vitamins is lower than expected. The most important factor in the prevention of the photo-aging and photocarcinogenesis is the sun protection at present.

Modelling low velocity impact induced damage in composite laminates

NASA Astrophysics Data System (ADS)

Shi, Yu; Soutis, Constantinos

2017-12-01

The paper presents recent progress on modelling low velocity impact induced damage in fibre reinforced composite laminates. It is important to understand the mechanisms of barely visible impact damage (BVID) and how it affects structural performance. To reduce labour intensive testing, the development of finite element (FE) techniques for simulating impact damage becomes essential and recent effort by the composites research community is reviewed in this work. The FE predicted damage initiation and propagation can be validated by Non Destructive Techniques (NDT) that gives confidence to the developed numerical damage models. A reliable damage simulation can assist the design process to optimise laminate configurations, reduce weight and improve performance of components and structures used in aircraft construction.

Mediators of Inflammation-Induced Bone Damage in Arthritis and Their Control by Herbal Products

PubMed Central

Nanjundaiah, Siddaraju M.; Astry, Brian; Moudgil, Kamal D.

2013-01-01

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation of the synovial joints leading to bone and cartilage damage. Untreated inflammatory arthritis can result in severe deformities and disability. The use of anti-inflammatory agents and biologics has been the mainstay of treatment of RA. However, the prolonged use of such agents may lead to severe adverse reactions. In addition, many of these drugs are quite expensive. These limitations have necessitated the search for newer therapeutic agents for RA. Natural plant products offer a promising resource for potential antiarthritic agents. We describe here the cellular and soluble mediators of inflammation-induced bone damage (osteoimmunology) in arthritis. We also elaborate upon various herbal products that possess antiarthritic activity, particularly mentioning the specific target molecules. As the use of natural product supplements by RA patients is increasing, this paper presents timely and useful information about the mechanism of action of promising herbal products that can inhibit the progression of inflammation and bone damage in the course of arthritis. PMID:23476694

Enhancement of deuterium retention in damaged tungsten by plasma-induced defect clustering

NASA Astrophysics Data System (ADS)

Jin, Younggil; Roh, Ki-Baek; Sheen, Mi-Hyang; Kim, Nam-Kyun; Song, Jaemin; Kim, Young-Woon; Kim, Gon-Ho

2017-12-01

The enhancement of deuterium retention was investigated for tungsten in the presence of both 2.8 MeV self-ion induced cascade damage and fuel hydrogen isotope plasma. Vacancy clustering in cascade damaged polycrystalline tungsten occurred due to deuterium irradiation and was observed near the grain boundary by using all-step transmission electron microscopy analysis. Analysis of the highest desorption temperature peak using thermal desorption spectroscopy supports reasonable evidence of defect clustering in the damaged polycrystalline tungsten. The defect clustering was neither observed on the damaged polycrystalline tungsten without deuterium irradiation nor on the damaged single-crystalline tungsten with deuterium irradiation. This result implies the synergetic role of deuterium and grain boundary on defect clustering. This study proposes a path for the defect transform from point defect to defect cluster, by the agglomeration between irradiated deuterium and cascade damage-induced defect. This agglomeration may induce more severe damage on the tungsten divertor at which the high fuel hydrogen ions, fast neutrons, and self-ions are irradiated simultaneously and it would increase the in-vessel tritium inventory.

Preventing Ultraviolet Light-Induced Damage: The Benefits of Antioxidants

ERIC Educational Resources Information Center

Yip, Cheng-Wai

2007-01-01

Extracts of fruit peels contain antioxidants that protect the bacterium "Escherichia coli" against damage induced by ultraviolet light. Antioxidants neutralise free radicals, thus preventing oxidative damage to cells and deoxyribonucleic acid. A high survival rate of UV-exposed cells was observed when grapefruit or grape peel extract was…

Tissue damage negatively regulates LPS-induced macrophage necroptosis.

PubMed

Li, Z; Scott, M J; Fan, E K; Li, Y; Liu, J; Xiao, G; Li, S; Billiar, T R; Wilson, M A; Jiang, Y; Fan, J

2016-09-01

Infection is a common clinical complication following tissue damage resulting from surgery and severe trauma. Studies have suggested that cell pre-activation by antecedent trauma/tissue damage profoundly impacts the response of innate immune cells to a secondary infectious stimulus. Cell necroptosis, a form of regulated inflammatory cell death, is one of the mechanisms that control cell release of inflammatory mediators from important innate immune executive cells such as macrophages (Mφ), which critically regulate the progress of inflammation. In this study, we investigated the mechanism and role of trauma/tissue damage in the regulation of LPS-induced Mφ necroptosis using a mouse model simulating long-bone fracture. We demonstrate that LPS acting through Toll-like receptor (TLR) 4 promotes Mφ necroptosis. However, necroptosis is ameliorated by high-mobility group box 1 (HMGB1) release from damaged tissue. We show that HMGB1 acting through cell surface receptor for advanced glycation end products (RAGE) upregulates caveolin-1 expression, which in turn induces caveolae-mediated TLR4 internalization and desensitization to decrease Mφ necroptosis. We further show that RAGE-MyD88 activation of Cdc42 and subsequent activation of transcription factor Sp1 serves as a mechanism underlying caveolin-1 transcriptional upregulation. These results reveal a previous unidentified protective role of damage-associated molecular pattern (DAMP) molecules in restricting inflammation in response to exogenous pathogen-associated molecular pattern molecules.

Tissue damage negatively regulates LPS-induced macrophage necroptosis

PubMed Central

Li, Z; Scott, M J; Fan, E K; Li, Y; Liu, J; Xiao, G; Li, S; Billiar, T R; Wilson, M A; Jiang, Y; Fan, J

2016-01-01

Infection is a common clinical complication following tissue damage resulting from surgery and severe trauma. Studies have suggested that cell pre-activation by antecedent trauma/tissue damage profoundly impacts the response of innate immune cells to a secondary infectious stimulus. Cell necroptosis, a form of regulated inflammatory cell death, is one of the mechanisms that control cell release of inflammatory mediators from important innate immune executive cells such as macrophages (Mφ), which critically regulate the progress of inflammation. In this study, we investigated the mechanism and role of trauma/tissue damage in the regulation of LPS-induced Mφ necroptosis using a mouse model simulating long-bone fracture. We demonstrate that LPS acting through Toll-like receptor (TLR) 4 promotes Mφ necroptosis. However, necroptosis is ameliorated by high-mobility group box 1 (HMGB1) release from damaged tissue. We show that HMGB1 acting through cell surface receptor for advanced glycation end products (RAGE) upregulates caveolin-1 expression, which in turn induces caveolae-mediated TLR4 internalization and desensitization to decrease Mφ necroptosis. We further show that RAGE-MyD88 activation of Cdc42 and subsequent activation of transcription factor Sp1 serves as a mechanism underlying caveolin-1 transcriptional upregulation. These results reveal a previous unidentified protective role of damage-associated molecular pattern (DAMP) molecules in restricting inflammation in response to exogenous pathogen-associated molecular pattern molecules. PMID:26943325

The ovarian DNA damage repair response is induced prior to phosphoramide mustard-induced follicle depletion, and ataxia telangiectasia mutated inhibition prevents PM-induced follicle depletion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ganesan, Shanthi, E-mail: shanthig@iastate.edu; Keating, Aileen F., E-mail: akeating@iastate.edu

Phosphoramide mustard (PM) is an ovotoxic metabolite of cyclophosphamide and destroys primordial and primary follicles potentially by DNA damage induction. The temporal pattern by which PM induces DNA damage and initiation of the ovarian response to DNA damage has not yet been well characterized. This study investigated DNA damage initiation, the DNA repair response, as well as induction of follicular demise using a neonatal rat ovarian culture system. Additionally, to delineate specific mechanisms involved in the ovarian response to PM exposure, utility was made of PKC delta (PKCδ) deficient mice as well as an ATM inhibitor (KU 55933; AI). Fishermore » 344 PND4 rat ovaries were cultured for 12, 24, 48 or 96 h in medium containing DMSO ± 60 μM PM or KU 55933 (48 h; 10 nM). PM-induced activation of DNA damage repair genes was observed as early as 12 h post-exposure. ATM, PARP1, E2F7, P73 and CASP3 abundance were increased but RAD51 and BCL2 protein decreased after 96 h of PM exposure. PKCδ deficiency reduced numbers of all follicular stages, but did not have an additive impact on PM-induced ovotoxicity. ATM inhibition protected all follicle stages from PM-induced depletion. In conclusion, the ovarian DNA damage repair response is active post-PM exposure, supporting that DNA damage contributes to PM-induced ovotoxicity. - Highlights: • PM exposure induces DNA damage repair gene expression. • Inhibition of ATM prevented PM-induced follicle depletion. • PKCδ deficiency did not impact PM-induced ovotoxicity.« less

Genoprotective and hepatoprotective effects of Guarana (Paullinia cupana Mart. var. sorbilis) on CCl4-induced liver damage in rats.

PubMed

Kober, Helena; Tatsch, Etiane; Torbitz, Vanessa Dorneles; Cargnin, Lara Peruzzolo; Sangoi, Manuela Borges; Bochi, Guilherme Vargas; da Silva, Andreia Regina Haas; Barbisan, Fernanda; Ribeiro, Euler Esteves; da Cruz, Ivana Beatrice Mânica; Moresco, Rafael Noal

2016-01-01

Several biological effects of Paullinia cupana (guarana) have been demonstrated, but little information is available on its effects on the liver. The current study was designed to evaluate the hepatoprotective and genoprotective effects of powder seeds from guarana on CCl4-induced liver injury in rats. Male Wistar rats were pretreated with guarana powder (100, 300 and 600 mg/kg) or silymarin 100 mg/kg daily for 14 days before treatment with a single dose of CCl4 (50% CCl4, 1 mL/kg, intraperitoneally). The treatment with CCl4 significantly increased the serum activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). In addition, CCl4 increased the DNA damage index in hepatocytes. Guarana in all concentrations was effective in decreasing the ALT and AST activities when compared with the CCl4-treated group. The treatment with guarana decreased DNA damage index when compared with the CCl4-treated group. In addition, the DNA damage index showed a significant positive correlation with AST and ALT. These results indicate that the guarana has hepatoprotective activity and prevents the DNA strand breakage in the CCl4-induced liver damage in rats.

Myostatin as a Marker for Doxorubicin Induced Cardiac Damage.

PubMed

Kesik, Vural; Honca, Tevfik; Gulgun, Mustafa; Uysal, Bulent; Kurt, Yasemin Gulcan; Cayci, Tuncer; Babacan, Oguzhan; Gocgeldi, Ercan; Korkmazer, Nadir

2016-01-01

Doxorubicin (DXR) is an effective chemotherapeutic agent but causes severe cardiac failure over known doses. Thus, early detection and prevention of cardiac damage is important. Various markers have been tested for early detection of cardiac damage. Myostatin is a protein produced in skeletal muscle cells inhibits muscle differentiation and growth during myogenesis. We evaluated the role of myostatin as a marker for showing DXR induced cardiac damage and compared with well known cardiac markers like NT-proBNP, hs-TnT and CK in a rat model of chronic DXR cardiotoxicity. Myostatin, NT-proBNP, and hs-TnT but not CK rose significantly during DXR treatment. Myostatin can be used as an early marker of DXR induced cardiotoxicity. © 2016 by the Association of Clinical Scientists, Inc.

Direct observation of ultrafast-electron-transfer reactions unravels high effectiveness of reductive DNA damage

PubMed Central

Nguyen, Jenny; Ma, Yuhan; Luo, Ting; Bristow, Robert G.; Jaffray, David A.; Lu, Qing-Bin

2011-01-01

Both water and electron-transfer reactions play important roles in chemistry, physics, biology, and the environment. Oxidative DNA damage is a well-known mechanism, whereas the relative role of reductive DNA damage is unknown. The prehydrated electron (), a novel species of electrons in water, is a fascinating species due to its fundamental importance in chemistry, biology, and the environment. is an ideal agent to observe reductive DNA damage. Here, we report both the first in situ femtosecond time-resolved laser spectroscopy measurements of ultrafast-electron-transfer (UET) reactions of with various scavengers (KNO3, isopropanol, and dimethyl sulfoxide) and the first gel electrophoresis measurements of DNA strand breaks induced by and OH• radicals co-produced by two-UV-photon photolysis of water. We strikingly found that the yield of reductive DNA strand breaks induced by each is twice the yield of oxidative DNA strand breaks induced by each OH• radical. Our results not only unravel the long-standing mystery about the relative role of radicals in inducing DNA damage under ionizing radiation, but also challenge the conventional notion that oxidative damage is the main pathway for DNA damage. The results also show the potential of femtomedicine as a new transdisciplinary frontier and the broad significance of UET reactions of in many processes in chemistry, physics, biology, and the environment. PMID:21730183

Ethanolic extract of Moringa oleifera Lam. leaves protect the pre-pubertal spermatogonial cells from cyclophosphamide-induced damage.

PubMed

Nayak, Guruprasad; Honguntikar, Sachin D; Kalthur, Sneha Guruprasad; D'Souza, Antony Sylvan; Mutalik, Srinivas; Setty, Manjunath M; Kalyankumar, Raksha; Krishnamurthy, Hanumanthappa; Kalthur, Guruprasad; Adiga, Satish Kumar

2016-04-22

Moringa oleifera Lam. is widely cultivated in Asian and African countries for its medicinal and dietary significance. The leaves are highly nutritious and are known to possess various biological activities. Pre-pubertal Swiss albino male mice were injected with single dose of cyclophosphamide (CP, 200mg/kg body weight) or ethanolic extract of Moringa oleifera leaves (MOE, 100mg/kg body weight) intraperitoneally. In combination group, MOE was administered 24h prior to CP injection. CP induced a significant decrease in testicular weight (p<0.01) and depletion of germ cells (p<0.001) and higher level of DNA damage (p<0.001) compared to control. The expression of P53, Bax, Cytochrome C (Cyt C) was increased while there was a decrease in the expression of Bcl2, c-Kit and Oct4. Administration of MOE 24h prior to CP treatment ameliorated the depletion (p<0.001), DNA damage (p<0.001) and apoptosis (p<0.01) of germ cells induced by CP. The mitigating effect of MOE appears to be mediated by up-regulating the expression of c-Kit and Oct4 transcripts in P53-independent manner. MOE protects the spermatogonial cells from CP-induced damage by modulating the apoptotic response elicited by CP and therefore can be considered as an efficient method of male fertility preservation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Eucalyptus globulus extract protects upon acetaminophen-induced kidney damages in male rat

PubMed Central

Dhibi, Sabah; Mbarki, Sakhria; Elfeki, Abdelfettah; Hfaiedh, Najla

2014-01-01

Plants have historically been used in treating many diseases. Eucalyptus globules, a rich source of bioactive compounds, and have been shown to possess antioxidative properties. The purpose of this study, carried out on male Wistar rats, was to evaluate the beneficial effects of Eucalyptus globulus extract upon acetaminophen-induced damages in kidney. Our study is realized in the Department of Biology, Faculty of Sciences of Sfax (Tunisia). 32 Wistar male rats; were divided into 4 batches: a control group (n=8), a group of rats treated with acetaminophen (goomg/kg) by intraperitoneal injection during 4 days (n=8), a group receiving Eucalyptus globulus extract (130 mg of dry leaves/kg/day) in drinking water during 42 days after 2 hours of acetaminophen administration (during 4 days) (n=8) and group received only Eucalyptus (n=8) during 42 days. After 6 weeks, animals from each group were rapidly sacrificed by decapitation. Blood serum was obtained by centrifugation. Under our experimental conditions, acetaminophen poisoning resulted in an oxidative stress evidenced by statistically significant losses in the activities of catalase (CAT), superoxide-dismutase (SOD), glutathione-peroxidase (GPX) activities and an increase in lipids peroxidation level in renal tissue of acetaminophen-treated group compared with the control group. Acetaminophen also caused kidney damage as evident by statistically significant (p<0.05) increase in levels of creatinine and urea and decreased levels of uric acid and proteins in blood. Histological analysis demonstrated alteration of proximal tubules, atrophy of the glomerule and dilatation of urinary space. Previous administration of plant extract is found to alleviate this acetaminophen-induced damage. PMID:24856382

Advances and New Concepts in Alcohol-Induced Organelle Stress, Unfolded Protein Responses and Organ Damage.

PubMed

Ji, Cheng

2015-06-03

Alcohol is a simple and consumable biomolecule yet its excessive consumption disturbs numerous biological pathways damaging nearly all organs of the human body. One of the essential biological processes affected by the harmful effects of alcohol is proteostasis, which regulates the balance between biogenesis and turnover of proteins within and outside the cell. A significant amount of published evidence indicates that alcohol and its metabolites directly or indirectly interfere with protein homeostasis in the endoplasmic reticulum (ER) causing an accumulation of unfolded or misfolded proteins, which triggers the unfolded protein response (UPR) leading to either restoration of homeostasis or cell death, inflammation and other pathologies under severe and chronic alcohol conditions. The UPR senses the abnormal protein accumulation and activates transcription factors that regulate nuclear transcription of genes related to ER function. Similarly, this kind of protein stress response can occur in other cellular organelles, which is an evolving field of interest. Here, I review recent advances in the alcohol-induced ER stress response as well as discuss new concepts on alcohol-induced mitochondrial, Golgi and lysosomal stress responses and injuries.

Changes in translation rate modulate stress-induced damage of diverse proteins

PubMed Central

Kim, Heejung

2013-01-01

Proteostasis is the maintenance of the proper function of cellular proteins. Hypertonic stress disrupts proteostasis and causes rapid and widespread protein aggregation and misfolding in the nematode Caenorhabditis elegans. Optimal survival in hypertonic environments requires degradation of damaged proteins. Inhibition of protein synthesis occurs in response to diverse environmental stressors and may function in part to minimize stress-induced protein damage. We recently tested this idea directly and demonstrated that translation inhibition by acute exposure to cycloheximide suppresses hypertonicity-induced aggregation of polyglutamine::YFP (Q35::YFP) in body wall muscle cells. In this article, we further characterized the relationship between protein synthesis and hypertonic stress-induced protein damage. We demonstrate that inhibition of translation reduces hypertonic stress-induced formation and growth of Q35::YFP, Q44::YFP, and α-synuclein aggregates; misfolding of paramyosin and ras GTPase; and aggregation of multiple endogenous proteins expressed in diverse cell types. Activation of general control nonderepressible-2 (GCN-2) kinase signaling during hypertonic stress inhibits protein synthesis via phosphorylation of eukaryotic initiation factor-2α (eIF-2α). Inhibition of GCN-2 activation prevents the reduction in translation rate and greatly exacerbates the formation and growth of Q35::YFP aggregates and the aggregation of endogenous proteins. The current studies together with our previous work provide the first direct demonstration that hypertonic stress-induced reduction in protein synthesis minimizes protein aggregation and misfolding. Reduction in translation rate also serves as a signal that activates osmoprotective gene expression. The cellular proteostasis network thus plays a critical role in minimizing hypertonic stress-induced protein damage, in degrading stress-damaged proteins, and in cellular osmosensing and signaling. PMID:24153430

Impact induced damage assessment by means of Lamb wave image processing

NASA Astrophysics Data System (ADS)

Kudela, Pawel; Radzienski, Maciej; Ostachowicz, Wieslaw

2018-03-01

The aim of this research is an analysis of full wavefield Lamb wave interaction with impact-induced damage at various impact energies in order to find out the limitation of the wavenumber adaptive image filtering method. In other words, the relation between impact energy and damage detectability will be shown. A numerical model based on the time domain spectral element method is used for modeling of Lamb wave propagation and interaction with barely visible impact damage in a carbon-epoxy laminate. Numerical studies are followed by experimental research on the same material with an impact damage induced by various energy and also a Teflon insert simulating delamination. Wavenumber adaptive image filtering and signal processing are used for damage visualization and assessment for both numerical and experimental full wavefield data. It is shown that it is possible to visualize and assess the impact damage location, size and to some extent severity by using the proposed technique.

Partial IGF-1 deficiency induces brain oxidative damage and edema, which are ameliorated by replacement therapy.

PubMed

Puche, Juan E; Muñoz, Úrsula; García-Magariño, Mariano; Sádaba, María C; Castilla-Cortázar, Inma

2016-01-01

Insulin-like growth factor 1 (IGF-1) induces multiple cytoprotective effects on every tissue, including the brain. Since the mechanisms by which IGF-1 produces neuroprotection are not fully understood, the aim of this work was to delve into the underlying mechanisms. IGF-1 deficient mice (Hz) were compared with wild type (WT) and Hz mice treated with low doses of IGF-1 (2 µg/100 g body weight/day) for 10 days (Hz + IGF). Gene expression, quantitative PCR, histology, and magnetic resonance imaging were performed in the three groups. IGF-1 deficiency induced increased oxidative damage determined by markers of lipid peroxidation and hypoxia, as well as gene expression of heat shock proteins, antioxidant enzymes, and molecules involved in inflammation, apoptosis, and mitochondrial protection. These changes correlated with edema and learning impairment in Hz mice. IGF-1 therapy improved all these alterations. In conclusion, IGF-1 deficiency is responsible for increased brain oxidative damage, edema, and impaired learning and memory capabilities which are rescued by IGF-1 replacement therapy. © 2016 International Union of Biochemistry and Molecular Biology.

Unrepaired DNA damage in macrophages causes elevation of particulate matter- induced airway inflammatory response.

PubMed

Luo, Man; Bao, Zhengqiang; Xu, Feng; Wang, Xiaohui; Li, Fei; Li, Wen; Chen, Zhihua; Ying, Songmin; Shen, Huahao

2018-04-14

The inflammatory cascade can be initiated with the recognition of damaged DNA. Macrophages play an essential role in particulate matter (PM)-induced airway inflammation. In this study, we aim to explore the PM induced DNA damage response of macrophages and its function in airway inflammation. The DNA damage response and inflammatory response were assessed using bone marrow-derived macrophages following PM treatment and mouse model instilled intratracheally with PM. We found that PM induced significant DNA damage both in vitro and in vivo and simultaneously triggered a rapid DNA damage response, represented by nuclear RPA, 53BP1 and γH2AX foci formation. Genetic ablation or chemical inhibition of the DNA damage response sensor amplified the production of cytokines including Cxcl1, Cxcl2 and Ifn-γ after PM stimulation in bone marrow-derived macrophages. Similar to that seen in vitro , mice with myeloid-specific deletion of RAD50 showed higher levels of airway inflammation in response to the PM challenge, suggesting a protective role of DNA damage sensor during inflammation. These data demonstrate that PM exposure induces DNA damage and activation of DNA damage response sensor MRN complex in macrophages. Disruption of MRN complex lead to persistent, unrepaired DNA damage that causes elevated inflammatory response.

Oxidant-induced DNA damage of target cells.

PubMed Central

Schraufstätter, I; Hyslop, P A; Jackson, J H; Cochrane, C G

1988-01-01

In this study we examined the leukocytic oxidant species that induce oxidant damage of DNA in whole cells. H2O2 added extracellularly in micromolar concentrations (10-100 microM) induced DNA strand breaks in various target cells. The sensitivity of a specific target cell was inversely correlated to its catalase content and the rate of removal of H2O2 by the target cell. Oxidant species produced by xanthine oxidase/purine or phorbol myristate acetate-stimulated monocytes induced DNA breakage of target cells in proportion to the amount of H2O2 generated. These DNA strand breaks were prevented by extracellular catalase, but not by superoxide dismutase. Cytotoxic doses of HOCl, added to target cells, did not induce DNA strand breakage, and myeloperoxidase added extracellularly in the presence of an H2O2-generating system, prevented the formation of DNA strand breaks in proportion to its H2O2 degrading capacity. The studies also indicated that H2O2 formed hydroxyl radical (.OH) intracellularly, which appeared to be the most likely free radical responsible for DNA damage: .OH was detected in cells exposed to H2O2; the DNA base, deoxyguanosine, was hydroxylated in cells exposed to H2O2; and intracellular iron was essential for induction of DNA strand breaks. PMID:2843565

PTEN positively regulates UVB-induced DNA damage repair

PubMed Central

Ming, Mei; Feng, Li; Shea, Christopher R.; Soltani, Keyoumars; Zhao, Baozhong; Han, Weinong; Smart, Robert C.; Trempus, Carol S.; He, Yu-Ying

2011-01-01

Non-melanoma skin cancer is the most common cancer in the U.S., where DNA-damaging UVB radiation from the sun remains the major environmental risk factor. However, the critical genetic targets of UVB radiation are undefined. Here we show that attenuating PTEN in epidermal keratinocytes is a predisposing factor for UVB-induced skin carcinogenesis in mice. In skin papilloma and squamous cell carcinoma (SCC), levels of PTEN were reduced compared to skin lacking these lesions. Likewise, there was a reduction in PTEN levels in human premalignant actinic keratosis and malignant SCC, supporting a key role for PTEN in human skin cancer formation and progression. PTEN downregulation impaired the capacity of global genomic nucleotide excision repair (GG-NER), a critical mechanism for removing UVB-induced mutagenic DNA lesions. In contrast to the response to ionizing radiation, PTEN downregulation prolonged UVB-induced growth arrest and increased the activation of the Chk1 DNA damage pathway in an AKT-independent manner, likely due to reduced DNA repair. PTEN loss also suppressed expression of the key GG-NER protein xeroderma pigmentosum C (XPC) through the AKT/p38 signaling axis. Reconstitution of XPC levels in PTEN-inhibited cells restored GG-NER capacity. Taken together, our findings define PTEN as an essential genomic gatekeeper in the skin, through its ability to positively regulate XPC-dependent GG-NER following DNA damage. PMID:21771908

Organic honey supplementation reverses pesticide-induced genotoxicity by modulating DNA damage response.

PubMed

Alleva, Renata; Manzella, Nicola; Gaetani, Simona; Ciarapica, Veronica; Bracci, Massimo; Caboni, Maria Fiorenza; Pasini, Federica; Monaco, Federica; Amati, Monica; Borghi, Battista; Tomasetti, Marco

2016-10-01

Glyphosate (GLY) and organophosphorus insecticides such as chlorpyrifos (CPF) may cause DNA damage and cancer in exposed individuals through mitochondrial dysfunction. Polyphenols ubiquitously present in fruits and vegetables, have been viewed as antioxidant molecules, but also influence mitochondrial homeostasis. Here, honey containing polyphenol compounds was evaluated for its potential protective effect on pesticide-induced genotoxicity. Honey extracts from four floral organic sources were evaluated for their polyphenol content, antioxidant activity, and potential protective effects on pesticide-related mitochondrial destabilization, reactive oxygen and nitrogen species formation, and DNA damage response in human bronchial epithelial and neuronal cells. The protective effect of honey was, then evaluated in a residential population chronically exposed to pesticides. The four honey types showed a different polyphenol profile associated with a different antioxidant power. The pesticide-induced mitochondrial dysfunction parallels ROS formation from mitochondria (mtROS) and consequent DNA damage. Honey extracts efficiently inhibited pesticide-induced mtROS formation, and reduced DNA damage by upregulation of DNA repair through NFR2. Honey supplementation enhanced DNA repair activity in a residential population chronically exposed to pesticides, which resulted in a marked reduction of pesticide-induced DNA lesions. These results provide new insight regarding the effect of honey containing polyphenols on pesticide-induced DNA damage response. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Mequindox induced cellular DNA damage via generation of reactive oxygen species.

PubMed

Liu, Jing; Ouyang, Man; Jiang, Jun; Mu, Peiqiang; Wu, Jun; Yang, Qi; Zhang, Caihui; Xu, Weiying; Wang, Lijuan; Huen, Michael S Y; Deng, Yiqun

2012-01-24

Mequindox, a quinoxaline-N-dioxide derivative that possesses antibacterial properties, has been widely used as a feed additive in the stockbreeding industry in China. While recent pharmacological studies have uncovered potential hazardous effects of mequindox, exactly how mequindox induces pathological changes and the cellular responses associated with its consumption remain largely unexplored. In this study, we investigated the cellular responses associated with mequindox treatment. We report here that mequindox inhibits cell proliferation by arresting cells at the G2/M phase of the cell cycle. Interestingly, this mequindox-associated deleterious effect on cell proliferation was observed in human, pig as well as chicken cells, suggesting that mequindox acts on evolutionarily conserved target(s). To further understand the mequindox-host interaction and the mechanism underlying mequindox-induced cell cycle arrest, we measured the cellular content of DNA damage, which is known to perturb cell proliferation and compromise cell survival. Accordingly, using γ-H2AX as a surrogate marker for DNA damage, we found that mequindox treatment induced cellular DNA damage, which paralleled the chemical-induced elevation of reactive oxygen species (ROS) levels. Importantly, expression of the antioxidant enzyme catalase partially alleviated these mequindox-associated effects. Taken together, our results suggest that mequindox cytotoxicity is attributable, in part, to its role as a potent inducer of DNA damage via ROS. © 2011 Elsevier B.V. All rights reserved.

Photoprotection beyond ultraviolet radiation--effective sun protection has to include protection against infrared A radiation-induced skin damage.

PubMed

Schroeder, P; Calles, C; Benesova, T; Macaluso, F; Krutmann, J

2010-01-01

Solar radiation is well known to damage human skin, for example by causing premature skin ageing (i.e. photoageing). We have recently learned that this damage does not result from ultraviolet (UV) radiation alone, but also from longer wavelengths, in particular near-infrared radiation (IRA radiation, 760-1,440 nm). IRA radiation accounts for more than one third of the solar energy that reaches human skin. While infrared radiation of longer wavelengths (IRB and IRC) does not penetrate deeply into the skin, more than 65% of the shorter wavelength (IRA) reaches the dermis. IRA radiation has been demonstrated to alter the collagen equilibrium of the dermal extracellular matrix in at least two ways: (a) by leading to an increased expression of the collagen-degrading enzyme matrix metalloproteinase 1, and (b) by decreasing the de novo synthesis of the collagen itself. IRA radiation exposure therefore induces similar biological effects to UV radiation, but the underlying mechanisms are substantially different, specifically, the cellular response to IRA irradiation involves the mitochondrial electron transport chain. Effective sun protection requires specific strategies to prevent IRA radiation-induced skin damage. 2010 S. Karger AG, Basel.

Characterization and modeling of low energy ion-induced damage in III-V semiconductors

NASA Astrophysics Data System (ADS)

Chen, Ching-Hui

1997-11-01

Low energy ion-induced damage (sub-keV) created during dry etching processes can extend quite deeply into materials. A systematic study on the deep penetration of dry etch-induced damage is necessary to improve device performance and helpful in further understanding the nature of defect propagation in semiconductors. In this study, a phenomenological model of dry etching damage that includes both effects of ion channeling and defect diffusion has been developed. It underscores that in addition to ion channeling, enhanced defect diffusion also plays an important role in establishing the damage profile. Further, the enhanced diffusion of dry etch- induced damage was experimentally observed for the first time by investigating the influences of concurrent above- bandgap laser illumination and low energy Ar+ ion bombardment on the damage profiles of GaAs/AlGaAs and InP-GaAs/InP heterostructures. The results indicate that non-radiative recombination of electron and hole pairs at defect sites is responsible for the observed radiation enhanced diffusion. DLTS measurements are also employed to characterize the nature of the enhanced diffusion in n-GaAs and reveal that a major component of the ion- induced defects is associated with primary point defects. Using the better understanding of the damage propagation in dry etched materials, a thin layer of low temperature grown GaAs (~200A) was utilized to stop defect propagation during dry etching process. This approach has been successfully applied to reduce ion damage that would occur during the formation of a dry-etch gate recess of a high electron mobility transistor. Finally, some future experiments are proposed and conceptually described, which would further clarify some of the many outstanding issues in the understanding and mitigation of etch- induced damage.

Ultraviolet radiation-induced interleukin 6 release in HeLa cells is mediated via membrane events in a DNA damage-independent way.

PubMed

Kulms, D; Pöppelmann, B; Schwarz, T

2000-05-19

Evidence exists that ultraviolet radiation (UV) affects molecular targets in the nucleus or at the cell membrane. UV-induced apoptosis was found to be mediated via DNA damage and activation of death receptors, suggesting that nuclear and membrane effects are not mutually exclusive. To determine whether participation of nuclear and membrane components is also essential for other UV responses, we studied the induction of interleukin-6 (IL-6) by UV. Exposing HeLa cells to UV at 4 degrees C, which inhibits activation of surface receptors, almost completely prevented IL-6 release. Enhanced repair of UV-mediated DNA damage by addition of the DNA repair enzyme photolyase did not affect UV-induced IL-6 production, suggesting that in this case membrane events predominant over nuclear effects. UV-induced IL-6 release is mediated via NFkappaB since the NFkappaB inhibitor MG132 or transfection of cells with a super-repressor form of the NFkappaB inhibitor IkappaB reduced IL-6 release. Transfection with a dominant negative mutant of the signaling protein TRAF-2 reduced IL-6 release upon exposure to UV, indicating that UV-induced IL-6 release is mediated by activation of the tumor necrosis factor receptor-1. These data demonstrate that UV can exert biological effects mainly by affecting cell surface receptors and that this is independent of its ability to induce nuclear DNA damage.

Revision of laser-induced damage threshold evaluation from damage probability data

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bataviciute, Gintare; Grigas, Povilas; Smalakys, Linas

2013-04-15

In this study, the applicability of commonly used Damage Frequency Method (DFM) is addressed in the context of Laser-Induced Damage Threshold (LIDT) testing with pulsed lasers. A simplified computer model representing the statistical interaction between laser irradiation and randomly distributed damage precursors is applied for Monte Carlo experiments. The reproducibility of LIDT predicted from DFM is examined under both idealized and realistic laser irradiation conditions by performing numerical 1-on-1 tests. A widely accepted linear fitting resulted in systematic errors when estimating LIDT and its error bars. For the same purpose, a Bayesian approach was proposed. A novel concept of parametricmore » regression based on varying kernel and maximum likelihood fitting technique is introduced and studied. Such approach exhibited clear advantages over conventional linear fitting and led to more reproducible LIDT evaluation. Furthermore, LIDT error bars are obtained as a natural outcome of parametric fitting which exhibit realistic values. The proposed technique has been validated on two conventionally polished fused silica samples (355 nm, 5.7 ns).« less

High-pressure-assisted X-ray-induced damage as a new route for materials synthesis

DOE PAGES

Evlyukhin, Egor; Kim, Eunja; Goldberger, David; ...

2018-01-01

X-ray radiation induced damage has been known for decades and has largely been viewed as a tremendous nuisance; e.g., most X-ray-related studies of organic and inorganic materials suffer X-ray damage to varying degrees. Although, recent theoretical and experimental investigation of the response of simple chemical systems to X-rays offered better understanding of the mechanistic details of X-ray induced damage, the question about useful applicability of this technique is still unclear. Furthermore we experimentally demonstrate that by tuning pressure and X-ray energy, the radiation induced damage can be controlled and used for synthesis of novel materials.

BMAL1 and CLOCK proteins in regulating UVB-induced apoptosis and DNA damage responses in human keratinocytes.

PubMed

Sun, Yang; Wang, Peiling; Li, Hongyu; Dai, Jun

2018-06-26

A diverse array of biological processes are under circadian controls. In mouse skin, ultraviolet ray (UVR)-induced apoptosis and DNA damage responses are time-of-day dependent, which are controlled by core clock proteins. This study investigates the roles of clock proteins in regulating UVB responses in human keratinocytes (HKCs). We found that the messenger RNA expression of brain and muscle ARNT-like 1 (BMAL1) and circadian locomotor output cycles kaput (CLOCK) genes is altered by low doses (5 mJ/cm 2 ) of UVB in the immortalized HaCat HKCs cell line. Although depletion of BMAL1 or CLOCK has no effect on the activation of Rad3-related protein kinases-checkpoint kinase 1-p53 mediated DNA damage checkpoints, it leads to suppression of UVB-stimulated apoptotic responses, and downregulation of UVB-elevated expression of DNA damage marker γ-H2AX and cell cycle inhibitor p21. Diminished apoptotic responses are also observed in primary HKCs depleted of BMAL1 or CLOCK after UVB irradiation. While CLOCK depletion shows a suppressive effect on UVB-induced p53 protein accumulation, depletion of either clock gene triggers early keratinocyte differentiation of HKCs at their steady state. These results suggest that UVB-induced apoptosis and DNA damage responses are controlled by clock proteins, but via different mechanisms in the immortalized human adult low calcium temperature and primary HKCs. Given the implication of UVB in photoaging and photocarcinogenesis, mechanistic elucidation of circadian controls on UVB effects in human skin will be critical and beneficial for prevention and treatment of skin cancers and other skin-related diseases. © 2018 Wiley Periodicals, Inc.

Potential role of punicalagin against oxidative stress induced testicular damage.

PubMed

Rao, Faiza; Tian, Hui; Li, Wenqing; Hung, Helong; Sun, Fei

2016-01-01

Punicalagin is isolated from pomegranate and widely used for the treatment of different diseases in Chinese traditional medicine. This study aimed to evaluate the effect of Punicalagin (purity ≥98%) on oxidative stress induced testicular damage and its effect on fertility. We detected the antioxidant potential of punicalagin in lipopolysaccharide (LPS) induced oxidative stress damage in testes, also tried to uncover the boosting fertility effect of Punicalagin (PU) against oxidative stress-induced infertility. Results demonstrated that 9 mg kg-1 for 7 days treatment significantly decreases LPS induced oxidative damage in testes and nitric oxide production. The administration of oxidative stress resulted in a significant reduction in testes antioxidants GSH, T-SOD, and CAT raised LPO, but treatment with punicalagin for 7 days increased antioxidant defense GSH, T-SOD, and CAT by the end of the experiment and reduced LPO level as well. PU also significantly activates Nrf2, which is involved in regulation of antioxidant defense systems. Hence, the present research categorically elucidates the protective effect of punicalagin against LPS induced oxidative stress induced perturbation in the process of spermatogenesis and significantly increased sperm health and number. Moreover, fertility success significantly decreased in LPS-injected mice compared to controls. Mice injected with LPS had fertility indices of 12.5%, while others treated with a combination of PU + LPS exhibited 75% indices. By promoting fertility and eliminating oxidative stress and inflammation, PU may be a useful nutrient for the treatment of infertility.

Potential role of punicalagin against oxidative stress induced testicular damage

PubMed Central

Rao, Faiza; Tian, Hui; Li, Wenqing; Hung, Helong; Sun, Fei

2016-01-01

Punicalagin is isolated from pomegranate and widely used for the treatment of different diseases in Chinese traditional medicine. This study aimed to evaluate the effect of Punicalagin (purity ≥98%) on oxidative stress induced testicular damage and its effect on fertility. We detected the antioxidant potential of punicalagin in lipopolysaccharide (LPS) induced oxidative stress damage in testes, also tried to uncover the boosting fertility effect of Punicalagin (PU) against oxidative stress-induced infertility. Results demonstrated that 9 mg kg−1 for 7 days treatment significantly decreases LPS induced oxidative damage in testes and nitric oxide production. The administration of oxidative stress resulted in a significant reduction in testes antioxidants GSH, T-SOD, and CAT raised LPO, but treatment with punicalagin for 7 days increased antioxidant defense GSH, T-SOD, and CAT by the end of the experiment and reduced LPO level as well. PU also significantly activates Nrf2, which is involved in regulation of antioxidant defense systems. Hence, the present research categorically elucidates the protective effect of punicalagin against LPS induced oxidative stress induced perturbation in the process of spermatogenesis and significantly increased sperm health and number. Moreover, fertility success significantly decreased in LPS-injected mice compared to controls. Mice injected with LPS had fertility indices of 12.5%, while others treated with a combination of PU + LPS exhibited 75% indices. By promoting fertility and eliminating oxidative stress and inflammation, PU may be a useful nutrient for the treatment of infertility. PMID:26763544

Damage of photoreceptor-derived cells in culture induced by light emitting diode-derived blue light

PubMed Central

Kuse, Yoshiki; Ogawa, Kenjiro; Tsuruma, Kazuhiro; Shimazawa, Masamitsu; Hara, Hideaki

2014-01-01

Our eyes are increasingly exposed to light from the emitting diode (LED) light of video display terminals (VDT) which contain much blue light. VDTs are equipped with televisions, personal computers, and smart phones. The present study aims to clarify the mechanism underlying blue LED light-induced photoreceptor cell damage. Murine cone photoreceptor-derived cells (661 W) were exposed to blue, white, or green LED light (0.38 mW/cm2). In the present study, blue LED light increased reactive oxygen species (ROS) production, altered the protein expression level, induced the aggregation of short-wavelength opsins (S-opsin), resulting in severe cell damage. While, blue LED light damaged the primary retinal cells and the damage was photoreceptor specific. N-Acetylcysteine (NAC), an antioxidant, protected against the cellular damage induced by blue LED light. Overall, the LED light induced cell damage was wavelength-, but not energy-dependent and may cause more severe retinal photoreceptor cell damage than the other LED light. PMID:24909301

Microcystin-LR induced DNA damage in human peripheral blood lymphocytes.

PubMed

Zegura, B; Gajski, G; Straser, A; Garaj-Vrhovac, V; Filipič, M

2011-12-24

Human exposure to microcystins, which are produced by freshwater cyanobacterial species, is of growing concern due to increasing appearance of cyanobacterial blooms as a consequence of global warming and increasing water eutrophication. Although microcystins are considered to be liver-specific, there is evidence that they may also affect other tissues. These substances have been shown to induce DNA damage in vitro and in vivo, but the mechanisms of their genotoxic activity remain unclear. In human peripheral blood lymphocytes (HPBLs) exposure to non-cytotoxic concentrations (0, 0.1, 1 and 10μg/ml) of microcystin-LR (MCLR) induced a dose- and time-dependent increase in DNA damage, as measured with the comet assay. Digestion of DNA from MCLR-treated HPBLs with purified formamidopyrimidine-DNA glycosylase (Fpg) displayed a greater number of DNA strand-breaks than non-digested DNA, confirming the evidence that MCLR induces oxidative DNA damage. With the cytokinesis-block micronucleus assay no statistically significant induction of micronuclei, nucleoplasmic bridges and nuclear buds was observed after a 24-h exposure to MCLR. At the molecular level, no changes in the expression of selected genes involved in the cellular response to DNA damage and oxidative stress were observed after a 4-h exposure to MCLR (1μg/ml). After 24h, DNA damage-responsive genes (p53, mdm2, gadd45a, cdkn1a), a gene involved in apoptosis (bax) and oxidative stress-responsive genes (cat, gpx1, sod1, gsr, gclc) were up-regulated. These results provide strong support that MCLR is an indirectly genotoxic agent, acting via induction of oxidative stress, and that lymphocytes are also the target of microcystin-induced toxicity. Copyright © 2011 Elsevier B.V. All rights reserved.

Prevention of Severe Hypoglycemia-Induced Brain Damage and Cognitive Impairment with Verapamil.

PubMed

Jackson, David A; Michael, Trevin; Vieira de Abreu, Adriana; Agrawal, Rahul; Bortolato, Marco; Fisher, Simon J

2018-05-03

People with insulin-treated diabetes are uniquely at risk for severe hypoglycemia-induced brain damage. Since calcium influx may mediate brain damage, we tested the hypothesis that the calcium channel blocker, verapamil, would significantly reduce brain damage and cognitive impairment caused by severe hypoglycemia. Ten-week-old Sprague-Dawley rats were randomly assigned to one of three treatments; 1) control hyperinsulinemic (200 mU.kg -1 min -1 ) euglycemic (80-100mg/dl) clamps (n=14), 2) hyperinsulinemic hypoglycemic (10-15mg/dl) clamps (n=16), or 3) hyperinsulinemic hypoglycemic clamps followed by a single treatment with verapamil (20mg/kg) (n=11). As compared to euglycemic controls, hypoglycemia markedly increased dead/dying neurons in the hippocampus and cortex, by 16-fold and 14-fold, respectively. Verapamil treatment strikingly decreased hypoglycemia-induced hippocampal and cortical damage, by 87% and 94%, respectively. Morris Water Maze probe trial results demonstrated that hypoglycemia induced a retention, but not encoding, memory deficit (noted by both abolished target quadrant preference and reduced target quadrant time). Verapamil treatment significantly rescued spatial memory as noted by restoration of target quadrant preference and target quadrant time. In summary, a one-time treatment with verapamil following severe hypoglycemia prevented neural damage and memory impairment caused by severe hypoglycemia. For people with insulin treated diabetes, verapamil may be a useful drug to prevent hypoglycemia-induced brain damage. © 2018 by the American Diabetes Association.

Aflatoxin B₁-Induced Developmental and DNA Damage in Caenorhabditis elegans.

PubMed

Feng, Wei-Hong; Xue, Kathy S; Tang, Lili; Williams, Phillip L; Wang, Jia-Sheng

2016-12-26

Aflatoxin B₁ (AFB₁) is a ubiquitous mycotoxin produced by toxicogenic Aspergillus species. AFB₁ has been reported to cause serious adverse health effects, such as cancers and abnormal development and reproduction, in animals and humans. AFB₁ is also a potent genotoxic mutagen that causes DNA damage in vitro and in vivo. However, the link between DNA damage and abnormal development and reproduction is unclear. To address this issue, we examined the DNA damage, germline apoptosis, growth, and reproductive toxicity following exposure to AFB₁, using Caenorhabditis elegans as a study model. Results found that AFB₁ induced DNA damage and germline apoptosis, and significantly inhibited growth and reproduction of the nematodes in a concentration-dependent manner. Exposure to AFB₁ inhibited growth or reproduction more potently in the DNA repair-deficient xpa-1 nematodes than the wild-type N2 strain. According to the relative expression level of pathway-related genes measured by real-time PCR, the DNA damage response (DDR) pathway was found to be associated with AFB₁-induced germline apoptosis, which further played an essential role in the dysfunction of growth and reproduction in C. elegans .

A Topical Mitochondria-Targeted Redox Cycling Nitroxide Mitigates Oxidative Stress Induced Skin Damage

PubMed Central

Brand, Rhonda M.; Epperly, Michael W.; Stottlemyer, J. Mark; Skoda, Erin M.; Gao, Xiang; Li, Song; Huq, Saiful; Wipf, Peter; Kagan, Valerian E.; Greenberger, Joel S.; Falo, Louis D.

2017-01-01

Skin is the largest human organ and provides a first line of defense that includes physical, chemical, and immune mechanisms to combat environmental stress. Radiation is a prevalent environmental stressor. Radiation induced skin damage ranges from photoaging and cutaneous carcinogenesis from UV exposure, to treatment-limiting radiation dermatitis associated with radiotherapy, to cutaneous radiation syndrome, a frequently fatal consequence of exposures from nuclear accidents. The major mechanism of skin injury common to these exposures is radiation induced oxidative stress. Efforts to prevent or mitigate radiation damage have included development of antioxidants capable of reducing reactive oxygen species (ROS). Mitochondria are particularly susceptible to oxidative stress, and mitochondrial dependent apoptosis plays a major role in radiation induced tissue damage. We reasoned that targeting a redox cycling nitroxide to mitochondria could prevent ROS accumulation, limiting downstream oxidative damage and preserving mitochondrial function. Here we show that in both mouse and human skin, topical application of a mitochondrial targeted antioxidant prevents and mitigates radiation induced skin damage characterized by clinical dermatitis, loss of barrier function, inflammation, and fibrosis. Further, damage mitigation is associated with reduced apoptosis, preservation of the skin’s antioxidant capacity, and reduction of irreversible DNA and protein oxidation associated with oxidative stress. PMID:27794421

Effect of SOS-induced levels of imuABC on spontaneous and damage-induced mutagenesis in Caulobacter crescentus.

PubMed

Alves, Ingrid R; Lima-Noronha, Marco A; Silva, Larissa G; Fernández-Silva, Frank S; Freitas, Aline Luiza D; Marques, Marilis V; Galhardo, Rodrigo S

2017-11-01

imuABC (imuAB dnaE2) genes are responsible for SOS-mutagenesis in Caulobacter crescentus and other bacterial species devoid of umuDC. In this work, we have constructed operator-constitutive mutants of the imuABC operon. We used this genetic tool to investigate the effect of SOS-induced levels of these genes upon both spontaneous and damage-induced mutagenesis. We showed that constitutive expression of imuABC does not increase spontaneous or damage-induced mutagenesis, nor increases cellular resistance to DNA-damaging agents. Nevertheless, the presence of the operator-constitutive mutation rescues mutagenesis in a recA background, indicating that imuABC are the only genes required at SOS-induced levels for translesion synthesis (TLS) in C. crescentus. Furthermore, these data also show that TLS mediated by ImuABC does not require RecA, unlike umuDC-dependent mutagenesis in E. coli. Copyright © 2017 Elsevier B.V. All rights reserved.

Escin-induced DNA damage promotes escin-induced apoptosis in human colorectal cancer cells via p62 regulation of the ATM/γH2AX pathway.

PubMed

Wang, Zhong; Chen, Qiang; Li, Bin; Xie, Jia-Ming; Yang, Xiao-Dong; Zhao, Kui; Wu, Yong; Ye, Zhen-Yu; Chen, Zheng-Rong; Qin, Zheng-Hong; Xing, Chun-Gen

2018-05-31

Escin, a triterpene saponin isolated from horse chestnut seed, has been used to treat encephaledema, tissue swelling and chronic venous insufficiency. Recent studies show that escin induces cell cycle arrest, tumor proliferation inhibition and tumor cell apoptosis. But the relationship between escin-induced DNA damage and cell apoptosis in tumor cells remains unclear. In this study, we investigated whether and how escin-induced DNA damage contributed to escin-induced apoptosis in human colorectal cancer cells. Escin (5-80 μg/mL) dose-dependently inhibited the cell viability and colony formation in HCT116 and HCT8 cells. Escin treatment induced DNA damage, leading to p-ATM and γH2AX upregulation. Meanwhile, escin treatment increased the expression of p62, an adaptor protein, which played a crucial role in controlling cell survival and tumorigenesis, and had a protective effect against escin-induced DNA damage: knockdown of p62 apparently enhanced escin-induced DNA damage, whereas overexpression of p62 reduced escin-induced DNA damage. In addition, escin treatment induced concentration- and time-dependent apoptosis. Similarly, knockdown of p62 significantly increased escin-induced apoptosis in vitro and produced en escin-like antitumor effect in vivo. Overexpression of p62 decreased the rate of apoptosis. Further studies revealed that the functions of p62 in escin-induced DNA damage were associated with escin-induced apoptosis, and p62 knockdown combined with the ATM inhibitor KU55933 augmented escin-induced DNA damage and further increased escin-induced apoptosis. In conclusion, our results demonstrate that p62 regulates ATM/γH2AX pathway-mediated escin-induced DNA damage and apoptosis.

The Involvement of the Oxidative Stress in Murine Blue LED Light-Induced Retinal Damage Model.

PubMed

Nakamura, Maho; Kuse, Yoshiki; Tsuruma, Kazuhiro; Shimazawa, Masamitsu; Hara, Hideaki

2017-01-01

The aim of study was to establish a mouse model of blue light emitting diode (LED) light-induced retinal damage and to evaluate the effects of the antioxidant N-acetylcysteine (NAC). Mice were exposed to 400 or 800 lx blue LED light for 2 h, and were evaluated for retinal damage 5 d later by electroretinogram amplitude and outer nuclear layer (ONL) thickness. Additionally, we investigated the effect of blue LED light exposure on shorts-wave-sensitive opsin (S-opsin), and rhodopsin expression by immunohistochemistry. Blue LED light induced light intensity dependent retinal damage and led to collapse of S-opsin and altered rhodopsin localization from inner and outer segments to ONL. Conversely, NAC administered at 100 or 250 mg/kg intraperitoneally twice a day, before dark adaptation and before light exposure. NAC protected the blue LED light-induced retinal damage in a dose-dependent manner. Further, blue LED light-induced decreasing of S-opsin levels and altered rhodopsin localization, which were suppressed by NAC. We established a mouse model of blue LED light-induced retinal damage and these findings indicated that oxidative stress was partially involved in blue LED light-induced retinal damage.

Cellular track model of biological damage to mammalian cell cultures from galactic cosmic rays

NASA Technical Reports Server (NTRS)

Cucinotta, Francis A.; Katz, Robert; Wilson, John W.; Townsend, Lawrence W.; Nealy, John E.; Shinn, Judy L.

1991-01-01

The assessment of biological damage from the galactic cosmic rays (GCR) is a current interest for exploratory class space missions where the highly ionizing, high-energy, high-charge ions (HZE) particles are the major concern. The relative biological effectiveness (RBE) values determined by ground-based experiments with HZE particles are well described by a parametric track theory of cell inactivation. Using the track model and a deterministic GCR transport code, the biological damage to mammalian cell cultures is considered for 1 year in free space at solar minimum for typical spacecraft shielding. Included are the effects of projectile and target fragmentation. The RBE values for the GCR spectrum which are fluence-dependent in the track model are found to be more severe than the quality factors identified by the International Commission on Radiological Protection publication 26 and seem to obey a simple scaling law with the duration period in free space.

The Effects of Creatine Supplementation on Exercise-Induced Muscle Damage.

ERIC Educational Resources Information Center

Rawson, Eric S.; Gunn, Bridget; Clarkson, Priscilla M.

2001-01-01

Investigated the effects of oral creatine (Cr) supplementation on markers of exercise-induced muscle damage following high-force eccentric exercise in men randomly administered Cr or placebo. Results indicated that 5 days of Cr supplementation did not reduce indirect makers of muscle damage or enhance recovery from high-force eccentric exercise.…

The effect of phytosterol protects rats against 4-nitrophenol-induced liver damage.

PubMed

Chen, Jiaqin; Song, Meiyan; Li, Yansen; Zhang, Yonghui; Taya, Kazuyoshi; Li, ChunMei

2016-01-01

We investigated the effect of phytosterol (PS) in regard to liver damage induced by 4-nitrophenol (PNP). Twenty rats were randomly divided into four groups (Control, PS, PNP, and PNP+PS). The PS and PNP+PS groups were pretreated with PS for one week. The PNP and PNP+PS groups were injected subcutaneously with PNP for 28 days. The control group received a basal diet and was injected with vehicle alone. Treatment with PS prevented the elevation of the total bilirubin levels, as well as an increase in serum alkaline transaminase and aspartate transaminase, which are typically caused by PNP-induced liver damage. Histopathologically showed that liver damage was significantly mitigated by PS treatment. However, there was no significant change in antioxidant enzyme activities, and the Nrf2-antioxidant system was not activated after treatment with PS. These results suggest that PS could mitigate liver damage induced by PNP, but does not enhance antioxidant capacity. Copyright © 2015 Elsevier B.V. All rights reserved.

Methimazole-induced hypothyroidism causes cellular damage in the spleen, heart, liver, lung and kidney.

PubMed

Cano-Europa, Edgar; Blas-Valdivia, Vanessa; Franco-Colin, Margarita; Gallardo-Casas, Carlos Angel; Ortiz-Butrón, Rocio

2011-01-01

It is known that a hypothyroidism-induced hypometabolic state protects against oxidative damage caused by toxins. However, some workers demonstrated that antithyroid drug-induced hypothyroidism can cause cellular damage. Our objective was to determine if methimazole (an antithyroid drug) or hypothyroidism causes cellular damage in the liver, kidney, lung, spleen and heart. Twenty-five male Wistar rats were divided into 5 groups: euthyroid, false thyroidectomy, thyroidectomy-induced hypothyroidism, methimazole-induced hypothyroidism (60 mg/kg), and treatment with methimazole (60 mg/kg) and a T₄ injection (20 μg/kg/d sc). At the end of the treatments (4 weeks for the pharmacological groups and 8 weeks for the surgical groups), the animals were anesthetized with sodium pentobarbital and they were transcardially perfused with 10% formaldehyde. The spleen, heart, liver, lung and kidney were removed and were processed for embedding in paraffin wax. Coronal sections were stained with hematoxylin-eosin. At the end of treatment, animals with both the methimazole- and thyroidectomy-induced hypothyroidism had a significant reduction of serum concentration of thyroid hormones. Only methimazole-induced hypothyroidism causes cellular damage in the kidney, lung, liver, heart, kidney and spleen. In addition, animals treated with methimazole and T₄ showed cellular damage in the lung, spleen and renal medulla with lesser damage in the liver, renal cortex and heart. The thyroidectomy only altered the lung structure. The alterations were prevented by T₄ completely in the heart and partially in the kidney cortex. These results indicate that tissue damage found in hypothyroidism is caused by methimazole. Copyright © 2009 Elsevier GmbH. All rights reserved.

UV and ionizing radiations induced DNA damage, differences and similarities

NASA Astrophysics Data System (ADS)

Ravanat, Jean-Luc; Douki, Thierry

2016-11-01

Both UV and ionizing radiations damage DNA. Two main mechanisms, so-called direct and indirect pathways, are involved in the degradation of DNA induced by ionizing radiations. The direct effect of radiation corresponds to direct ionization of DNA (one electron ejection) whereas indirect effects are produced by reactive oxygen species generated through water radiolysis, including the highly reactive hydroxyl radicals, which damage DNA. UV (and visible) light damages DNA by again two distinct mechanisms. UVC and to a lesser extend UVB photons are directly absorbed by DNA bases, generating their excited states that are at the origin of the formation of pyrimidine dimers. UVA (and visible) light by interaction with endogenous or exogenous photosensitizers induce the formation of DNA damage through photosensitization reactions. The excited photosensitizer is able to induce either a one-electron oxidation of DNA (type I) or to produce singlet oxygen (type II) that reacts with DNA. In addition, through an energy transfer from the excited photosensitizer to DNA bases (sometime called type III mechanism) formation of pyrimidine dimers could be produced. Interestingly it has been shown recently that pyrimidine dimers are also produced by direct absorption of UVA light by DNA, even if absorption of DNA bases at these wavelengths is very low. It should be stressed that some excited photosensitizers (such as psoralens) could add directly to DNA bases to generate adducts. The review will described the differences and similarities in terms of damage formation (structure and mechanisms) between these two physical genotoxic agents.

Lipids and Oxidative Stress Associated with Ethanol-Induced Neurological Damage

PubMed Central

2016-01-01

The excessive intake of alcohol is a serious public health problem, especially given the severe damage provoked by chronic or prenatal exposure to alcohol that affects many physiological processes, such as memory, motor function, and cognitive abilities. This damage is related to the ethanol oxidation in the brain. The metabolism of ethanol to acetaldehyde and then to acetate is associated with the production of reactive oxygen species that accentuate the oxidative state of cells. This metabolism of ethanol can induce the oxidation of the fatty acids in phospholipids, and the bioactive aldehydes produced are known to be associated with neurotoxicity and neurodegeneration. As such, here we will review the role of lipids in the neuronal damage induced by ethanol-related oxidative stress and the role that lipids play in the related compensatory or defense mechanisms. PMID:26949445

Edaravone Protect against Retinal Damage in Streptozotocin-Induced Diabetic Mice

PubMed Central

Liu, Xiaoyi; Chen, Xi; Xie, Ping; Yuan, Songtao; Zhang, Weiwei; Lin, Xiaojun; Liu, Qinghuai

2014-01-01

Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one), a free radical scavenger, is used for the clinical treatment of retinal injury. In this study, we investigated the protective effects of edaravone against diabetic retinal damage in the mouse. Diabetic retinopathy in the mouse was induced by injection of streptozotocin. Edaravone was given once-daily and was intraperitoneally (i.p.) treated at a dose of 3 mg/kg from streptozotocin injection to 4 weeks after onset of diabetes. Retinal ganglion cells (RGCs) damage was evaluated by recording the pattern electroretinogram (ERG). RGCs damage was also detected by Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, and the levels of reactive oxygen species (ROS) were determined fluorometrically. The expressions of phosporylated-ERK1/2, BDNF, and caspase-3 were determined by Western blot analysis. Retinal levels of ROS, phosphorylated ERK1/2, and cleaved caspase-3 were significantly increased, whereas the expression of BDNF was significantly decreased in the retinas of diabetic mice, compared to nondiabetic mice. Administration of edaravone significantly attenuated diabetes induced RGCs death, upregulation of ROS, ERK1/2 phosphorylation, and cleaved caspase-3 and downregulation of BDNF. These findings suggest that oxidative stress plays a pivotal role in diabetic retinal damage and that systemic administration of edaravone may slow the progression of retinal neuropathy induced by diabetes. PMID:24897298

Edaravone protect against retinal damage in streptozotocin-induced diabetic mice.

PubMed

Yuan, Dongqing; Xu, Yidan; Hang, Hui; Liu, Xiaoyi; Chen, Xi; Xie, Ping; Yuan, Songtao; Zhang, Weiwei; Lin, Xiaojun; Liu, Qinghuai

2014-01-01

Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one), a free radical scavenger, is used for the clinical treatment of retinal injury. In this study, we investigated the protective effects of edaravone against diabetic retinal damage in the mouse. Diabetic retinopathy in the mouse was induced by injection of streptozotocin. Edaravone was given once-daily and was intraperitoneally (i.p.) treated at a dose of 3 mg/kg from streptozotocin injection to 4 weeks after onset of diabetes. Retinal ganglion cells (RGCs) damage was evaluated by recording the pattern electroretinogram (ERG). RGCs damage was also detected by Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, and the levels of reactive oxygen species (ROS) were determined fluorometrically. The expressions of phosporylated-ERK1/2, BDNF, and caspase-3 were determined by Western blot analysis. Retinal levels of ROS, phosphorylated ERK1/2, and cleaved caspase-3 were significantly increased, whereas the expression of BDNF was significantly decreased in the retinas of diabetic mice, compared to nondiabetic mice. Administration of edaravone significantly attenuated diabetes induced RGCs death, upregulation of ROS, ERK1/2 phosphorylation, and cleaved caspase-3 and downregulation of BDNF. These findings suggest that oxidative stress plays a pivotal role in diabetic retinal damage and that systemic administration of edaravone may slow the progression of retinal neuropathy induced by diabetes.

NLRP3 Inflammasome Mediates Aldosterone-Induced Vascular Damage.

PubMed

Bruder-Nascimento, Thiago; Ferreira, Nathanne S; Zanotto, Camila Z; Ramalho, Fernanda; Pequeno, Isabela O; Olivon, Vania C; Neves, Karla B; Alves-Lopes, Rheure; Campos, Eduardo; Silva, Carlos Alberto A; Fazan, Rubens; Carlos, Daniela; Mestriner, Fabiola L; Prado, Douglas; Pereira, Felipe V; Braga, Tarcio; Luiz, Joao Paulo M; Cau, Stefany B; Elias, Paula C; Moreira, Ayrton C; Câmara, Niels O; Zamboni, Dario S; Alves-Filho, Jose Carlos; Tostes, Rita C

2016-12-06

Inflammation is a key feature of aldosterone-induced vascular damage and dysfunction, but molecular mechanisms by which aldosterone triggers inflammation remain unclear. The NLRP3 inflammasome is a pivotal immune sensor that recognizes endogenous danger signals triggering sterile inflammation. We analyzed vascular function and inflammatory profile of wild-type (WT), NLRP3 knockout (NLRP3 -/- ), caspase-1 knockout (Casp-1 -/- ), and interleukin-1 receptor knockout (IL-1R -/- ) mice treated with vehicle or aldosterone (600 µg·kg -1 ·d -1 for 14 days through osmotic mini-pump) while receiving 1% saline to drink. Here, we show that NLRP3 inflammasome plays a central role in aldosterone-induced vascular dysfunction. Long-term infusion of aldosterone in mice resulted in elevation of plasma interleukin-1β levels and vascular abnormalities. Mice lacking the IL-1R or the inflammasome components NLRP3 and caspase-1 were protected from aldosterone-induced vascular damage. In vitro, aldosterone stimulated NLRP3-dependent interleukin-1β secretion by bone marrow-derived macrophages by activating nuclear factor-κB signaling and reactive oxygen species generation. Moreover, chimeric mice reconstituted with NLRP3-deficient hematopoietic cells showed that NLRP3 in immune cells mediates aldosterone-induced vascular damage. In addition, aldosterone increased the expression of NLRP3, active caspase-1, and mature interleukin-1β in human peripheral blood mononuclear cells. Hypertensive patients with hyperaldosteronism or normal levels of aldosterone exhibited increased activity of NLRP3 inflammasome, suggesting that the effect of hyperaldosteronism on the inflammasome may be mediated through high blood pressure. Together, these data demonstrate that NLRP3 inflammasome, through activation of IL-1R, is critically involved in the deleterious vascular effects of aldosterone, placing NLRP3 as a potential target for therapeutic interventions in conditions with high aldosterone levels. �

Dissecting the Molecular Mechanism of Ionizing Radiation-Induced Tissue Damage in the Feather Follicle

PubMed Central

Chen, Xi; Liao, Chunyan; Chu, Qiqi; Zhou, Guixuan; Lin, Xiang; Li, Xiaobo; Lu, Haijie; Xu, Benhua; Yue, Zhicao

2014-01-01

Ionizing radiation (IR) is a common therapeutic agent in cancer therapy. It damages normal tissue and causes side effects including dermatitis and mucositis. Here we use the feather follicle as a model to investigate the mechanism of IR-induced tissue damage, because any perturbation of feather growth will be clearly recorded in its regular yet complex morphology. We find that IR induces defects in feather formation in a dose-dependent manner. No abnormality was observed at 5 Gy. A transient, reversible perturbation of feather growth was induced at 10 Gy, leading to defects in the feather structure. This perturbation became irreversible at 20 Gy. Molecular and cellular analysis revealed P53 activation, DNA damage and repair, cell cycle arrest and apoptosis in the pathobiology. IR also induces patterning defects in feather formation, with disrupted branching morphogenesis. This perturbation is mediated by cytokine production and Stat1 activation, as manipulation of cytokine levels or ectopic Stat1 over-expression also led to irregular feather branching. Furthermore, AG-490, a chemical inhibitor of Stat1 signaling, can partially rescue IR-induced tissue damage. Our results suggest that the feather follicle could serve as a useful model to address the in vivo impact of the many mechanisms of IR-induced tissue damage. PMID:24586618

Enhanced thermomechanical stability on laser-induced damage by functionally graded layers in quasi-rugate filters

NASA Astrophysics Data System (ADS)

Pu, Yunti; Ma, Ping; Lv, Liang; Zhang, Mingxiao; Lu, Zhongwen; Qiao, Zhao; Qiu, Fuming

2018-05-01

Ta2O5-SiO2 quasi-rugate filters with a reasonable optimization of rugate notch filter design were prepared by ion-beam sputtering. The optical properties and laser-induced damage threshold are studied. Compared with the spectrum of HL-stacks, the spectrum of quasi-rugate filters have weaker second harmonic peaks and narrower stopbands. According to the effect of functionally graded layers (FGLs), 1-on-1 and S-on-1 Laser induced damage threshold (LIDT) of quasi-rugate filters are about 22% and 50% higher than those of HL stacks, respectively. Through the analysis of the damage morphologies, laser-induced damage of films under nanosecond multi-pulse are dominated by a combination of thermal shock stress and thermomechanical instability due to nodules. Compared with catastrophic damages, the damage sits of quasi-rugate filters are developed in a moderate way. The damage growth behavior of defect-induced damage sites have been effectively restrained by the structure of FGLs. Generally, FGLs are used to reduce thermal stress by the similar thermal-expansion coefficients of neighboring layers and solve the problems such as instability and cracking raised by the interface discontinuity of nodular boundaries, respectively.

Fluoride induces oxidative damage and SIRT1/autophagy through ROS-mediated JNK signaling.

PubMed

Suzuki, Maiko; Bandoski, Cheryl; Bartlett, John D

2015-12-01

Fluoride is an effective caries prophylactic, but at high doses can also be an environmental health hazard. Acute or chronic exposure to high fluoride doses can result in dental enamel and skeletal and soft tissue fluorosis. Dental fluorosis is manifested as mottled, discolored, porous enamel that is susceptible to dental caries. Fluoride induces cell stress, including endoplasmic reticulum stress and oxidative stress, which leads to impairment of ameloblasts responsible for dental enamel formation. Recently we reported that fluoride activates SIRT1 and autophagy as an adaptive response to protect cells from stress. However, it still remains unclear how SIRT1/autophagy is regulated in dental fluorosis. In this study, we demonstrate that fluoride exposure generates reactive oxygen species (ROS) and the resulting oxidative damage is counteracted by SIRT1/autophagy induction through c-Jun N-terminal kinase (JNK) signaling in ameloblasts. In the mouse-ameloblast-derived cell line LS8, fluoride induced ROS, mitochondrial damage including cytochrome-c release, up-regulation of UCP2, attenuation of ATP synthesis, and H2AX phosphorylation (γH2AX), which is a marker of DNA damage. We evaluated the effects of the ROS inhibitor N-acetylcysteine (NAC) and the JNK inhibitor SP600125 on fluoride-induced SIRT1/autophagy activation. NAC decreased fluoride-induced ROS generation and attenuated JNK and c-Jun phosphorylation. NAC decreased SIRT1 phosphorylation and formation of the autophagy marker LC3II, which resulted in an increase in the apoptosis mediators γH2AX and cleaved/activated caspase-3. SP600125 attenuated fluoride-induced SIRT1 phosphorylation, indicating that fluoride activates SIRT1/autophagy via the ROS-mediated JNK pathway. In enamel organs from rats or mice treated with 50, 100, or 125 ppm fluoride for 6 weeks, cytochrome-c release and the DNA damage markers 8-oxoguanine, p-ATM, and γH2AX were increased compared to those in controls (0 ppm fluoride). These

Fluoride induces oxidative damage and SIRT1/autophagy through ROS-mediated JNK signaling

PubMed Central

Suzuki, Maiko; Bandoski, Cheryl; Bartlett, John D.

2015-01-01

Fluoride is an effective caries prophylactic, but at high doses can also be an environmental health hazard. Acute or chronic exposure to high fluoride doses can result in dental enamel and skeletal and soft tissue fluorosis. Dental fluorosis is manifested as mottled, discolored, porous enamel that is susceptible to dental caries. Fluoride induces cell stress, including endoplasmic reticulum stress and oxidative stress, which leads to impairment of ameloblasts responsible for dental enamel formation. Recently we reported that fluoride activates SIRT1 and autophagy as an adaptive response to protect cells from stress. However, it still remains unclear how SIRT1/autophagy is regulated in dental fluorosis. In this study, we demonstrate that fluoride exposure generates reactive oxygen species (ROS) and the resulting oxidative damage is counteracted by SIRT1/autophagy induction through c-Jun N-terminal kinase (JNK) signaling in ameloblasts. In the mouse-ameloblast-derived cell line LS8, fluoride induced ROS, mitochondrial damage including cytochrome-c release, up-regulation of UCP2, attenuation of ATP synthesis, and H2AX phosphorylation (γH2AX), which is a marker of DNA damage. We evaluated the effects of the ROS inhibitor N-acetylcysteine (NAC) and the JNK inhibitor SP600125 on fluoride-induced SIRT1/autophagy activation. NAC decreased fluoride-induced ROS generation and attenuated JNK and c-Jun phosphorylation. NAC decreased SIRT1 phosphorylation and formation of the autophagy marker LC3II, which resulted in an increase in the apoptosis mediators γH2AX and cleaved/activated caspase-3. SP600125 attenuated fluoride-induced SIRT1 phosphorylation, indicating that fluoride activates SIRT1/autophagy via the ROS-mediated JNK pathway. In enamel organs from rats or mice treated with 50, 100, or 125 ppm fluoride for 6 weeks, cytochrome-c release and the DNA damage markers 8-oxoguanine, p-ATM, and γH2AX were increased compared to those in controls (0 ppm fluoride). These

Laser-induced damage threshold of camera sensors and micro-optoelectromechanical systems

NASA Astrophysics Data System (ADS)

Schwarz, Bastian; Ritt, Gunnar; Koerber, Michael; Eberle, Bernd

2017-03-01

The continuous development of laser systems toward more compact and efficient devices constitutes an increasing threat to electro-optical imaging sensors, such as complementary metal-oxide-semiconductors (CMOS) and charge-coupled devices. These types of electronic sensors are used in day-to-day life but also in military or civil security applications. In camera systems dedicated to specific tasks, micro-optoelectromechanical systems, such as a digital micromirror device (DMD), are part of the optical setup. In such systems, the DMD can be located at an intermediate focal plane of the optics and it is also susceptible to laser damage. The goal of our work is to enhance the knowledge of damaging effects on such devices exposed to laser light. The experimental setup for the investigation of laser-induced damage is described in detail. As laser sources, both pulsed lasers and continuous-wave (CW)-lasers are used. The laser-induced damage threshold is determined by the single-shot method by increasing the pulse energy from pulse to pulse or in the case of CW-lasers, by increasing the laser power. Furthermore, we investigate the morphology of laser-induced damage patterns and the dependence of the number of destructive device elements on the laser pulse energy or laser power. In addition to the destruction of single pixels, we observe aftereffects, such as persistent dead columns or rows of pixels in the sensor image.

Sulforaphane protects against cytokine- and streptozotocin-induced {beta}-cell damage by suppressing the NF-{kappa}B pathway

DOE Office of Scientific and Technical Information (OSTI.GOV)

Song, Mi-Young; Kim, Eun-Kyung; Moon, Woo-Sung

2009-02-15

Sulforaphane (SFN) is an indirect antioxidant that protects animal tissues from chemical or biological insults by stimulating the expression of several NF-E2-related factor-2 (Nrf2)-regulated phase 2 enzymes. Treatment of RINm5F insulinoma cells with SFN increases Nrf2 nuclear translocation and expression of phase 2 enzymes. In this study, we investigated whether the activation of Nrf2 by SFN treatment or ectopic overexpression of Nrf2 inhibited cytokine-induced {beta}-cell damage. Treatment of RIN cells with IL-1{beta} and IFN-{gamma} induced {beta}-cell damage through a NF-{kappa}B-dependent signaling pathway. Activation of Nrf2 by treatment with SFN and induction of Nrf2 overexpression by transfection with Nrf2 prevented cytokinemore » toxicity. The mechanism by which Nrf2 activation inhibited NF-{kappa}B-dependent cell death signals appeared to involve the reduction of oxidative stress, as demonstrated by the inhibition of cytokine-induced H{sub 2}O{sub 2} production. The protective effect of SFN was further demonstrated by the restoration of normal insulin secreting responses to glucose in cytokine-treated rat pancreatic islets. Furthermore, pretreatment with SFN blocked the development of type 1 diabetes in streptozotocin-treated mice.« less

Radiation-Induced Liver Damage: Correlation of Histopathology with Hepatobiliary Magnetic Resonance Imaging, a Feasibility Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Seidensticker, Max, E-mail: max.seidensticker@med.ovgu.de; Burak, Miroslaw; Kalinski, Thomas

PurposeRadiotherapy of liver malignancies shows promising results (radioembolization, stereotactic irradiation, interstitial brachytherapy). Regardless of the route of application, a certain amount of nontumorous liver parenchyma will be collaterally damaged by radiation. The functional reserve may be significantly reduced with an impact on further treatment planning. Monitoring of radiation-induced liver damage by imaging is neither established nor validated. We performed an analysis to correlate the histopathological presence of radiation-induced liver damage with functional magnetic resonance imaging (MRI) utilizing hepatobiliary contrast media (Gd-BOPTA).MethodsPatients undergoing local high-dose-rate brachytherapy for whom a follow-up hepatobiliary MRI within 120 days after radiotherapy as well as an evaluablemore » liver biopsy from radiation-exposed liver tissue within 7 days before MRI were retrospectively identified. Planning computed tomography (CT)/dosimetry was merged to the CT-documentation of the liver biopsy and to the MRI. Presence/absence of radiation-induced liver damage (histopathology) and Gd-BOPTA uptake (MRI) as well as the dose applied during brachytherapy at the site of tissue sampling was determined.ResultsFourteen biopsies from eight patients were evaluated. In all cases with histopathological evidence of radiation-induced liver damage (n = 11), no uptake of Gd-BOPTA was seen. In the remaining three, cases no radiation-induced liver damage but Gd-BOPTA uptake was seen. Presence of radiation-induced liver damage and absence of Gd-BOPTA uptake was correlated with a former high-dose exposition.ConclusionsAbsence of hepatobiliary MRI contrast media uptake in radiation-exposed liver parenchyma may indicate radiation-induced liver damage. Confirmatory studies are warranted.« less

Chronic intermittent hypobaric hypoxia attenuates radiation induced heart damage in rats.

PubMed

Wang, Jun; Wu, Yajing; Yuan, Fang; Liu, Yixian; Wang, Xuefeng; Cao, Feng; Zhang, Yi; Wang, Sheng

2016-09-01

Radiation-induced heart damage (RIHD) is becoming an increasing concern for patients and clinicians due to the use of radiotherapy for thoracic tumor. Chronic intermittent hypobaric hypoxia (CIHH) preconditioning has been documented to exert a cardioprotective effect. Here we hypothesized that CIHH was capable of attenuating functional and structural damage in a rat model of RIHD. Male adult Sprague-Dawley rats were randomly divided into 4 groups: control, radiation, CIHH and CIHH plus radiation. Cardiac function was measured using Langendorff perfusion in in vitro rat hearts. Cardiac fibrosis, oxidative stress and endoplasmic reticulum stress (ERS) was assessed by quantitative analysis of protein expression. No significant difference between any two groups was observed in baseline cardiac function as assessed by left ventricular end diastolic pressure (LVEDP), left ventricular developing pressure (LVDP) and the derivative of left ventricular pressure (±LVdp/dt). When challenged by ischemia/reperfusion, LVEDP was increased but LVDP and ±LVdp/dt was decreased significantly in radiation group compared with controls, accompanied by an enlarged infarct size and decreased coronary flow. Importantly, CIHH dramatically improved radiation-induced damage of cardiac function and blunted radiation-induced cardiac fibrosis in the perivascular and interstitial area. Furthermore, CIHH abrogated radiation-induced increase in malondialdehyde and enhanced total superoxide dismutase activity, as well as downregulated expression levels of ERS markers like GRP78 and CHOP. CIHH pretreatment alleviated radiation-induced damage of cardiac function and fibrosis. Such a protective effect was closely associated with suppression of oxidative stress and ERS responses. Copyright © 2016 Elsevier Inc. All rights reserved.

Diagnostics for the detection and evaluation of laser induced damage

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sheehan, L.; Kozlowski, M.; Rainer, F.

1995-12-31

The Laser Damage and Conditioning Group at LLNL is evaluating diagnostics which will help make damage testing more efficient and reduce the risk of damage during laser conditioning. The work to date has focused on photoacoustic and scattered light measurements on 1064-nm wavelength HfO{sub 2}/SiO{sub 2} multilayer mirror and polarizer coatings. Both the acoustic and scatter diagnostics have resolved 10 {mu}m diameter damage points in these coatings. Using a scanning stage, the scatter diagnostic can map both intrinsic and laser-induced scatter. Damage threshold measurements obtained using scatter diagnostics compare within experimental error with those measured using 100x Nomarski microscopy. Scattermore » signals measured during laser conditioning can be used to detect damage related to nodular defects.« less

Diagnostics for the detection and evaluation of laser induced damage

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sheehan, L.; Kozlowski, M.; Rainer, F.

1995-01-03

The Laser Damage and Conditioning Group at LLNL is evaluating diagnostics which will help make damage testing more efficient and reduce the risk of damage during laser conditioning. The work to date has focused on photoacoustic and scattered light measurements on 1064-nm wavelength HfO{sub 2}/SiO{sub 2} multilayer mirror and polarizer coatings. Both the acoustic and scatter diagnostics have resolved 10 {mu}m diameter damage points in these coatings. Using a scanning stage, the scatter diagnostic can map both intrinsic and laser-induced scatter. Damage threshold measurements obtained using scatter diagnostics compare within experimental error with those measured using 100x Nomarski microscopy. Scattermore » signals measured during laser conditioning can be used to detect damage related to nodular defects.« less

Alleviation by garlic of antitumor drug-induced damage to the intestine.

PubMed

Horie, T; Awazu, S; Itakura, Y; Fuwa, T

2001-03-01

Antitumour drugs such as methotrexate (MTX) and 5-fluorouracil (5-FU) induce intestinal damage. This is a serious side effect of cancer chemotherapy. The present studies examined whether or not aged garlic extract (AGE) protects against damage from these antitumor drugs. Both drugs were administered orally for 4 or 5 d to rats fed a standard laboratory diet with and without 2% AGE. The small intestinal absorption of the poorly absorbable compound, fluorescein isothiocyanate--labeled dextran (FD-4; average molecular weight, 4400) was used to evaluate the damage to the intestine using the in vitro everted intestine technique and the in situ intestinal loop technique. FD-4 absorption increased in the antitumour drug-treated rats fed the diet without garlic. Interestingly, FD-4 absorption was depressed in rats fed the diet containing AGE. These results suggest that AGE may protect the small intestine of rats from antitumour drug-induced damage.

Effects of allopurinol on exercise-induced muscle damage: new therapeutic approaches?

PubMed

Sanchis-Gomar, F; Pareja-Galeano, H; Perez-Quilis, C; Santos-Lozano, A; Fiuza-Luces, C; Garatachea, N; Lippi, G; Lucia, A

2015-01-01

Intensive muscular activity can trigger oxidative stress, and free radicals may hence be generated by working skeletal muscle. The role of the enzyme xanthine oxidase as a generating source of free radicals is well documented and therefore is involved in the skeletal muscle damage as well as in the potential transient cardiovascular damage induced by high-intensity physical exercise. Allopurinol is a purine hypoxanthine-based structural analog and a well-known inhibitor of xanthine oxidase. The administration of the xanthine oxidase inhibitor allopurinol may hence be regarded as promising, safe, and an economic strategy to decrease transient skeletal muscle damage (as well as heart damage, when occurring) in top-level athletes when administered before a competition or a particularly high-intensity training session. Although continuous administration of allopurinol in high-level athletes is not recommended due to its possible role in hampering training-induced adaptations, the drug might be useful in non-athletes. Exertional rhabdomyolysis is the most common form of rhabdomyolysis and affects individuals participating in a type of intense exercise to which they are not accustomed. This condition can cause exercise-related myoglobinuria, thus increasing the risk of acute renal failure and is also associated with sickle cell trait. In this manuscript, we have reviewed the recent evidence about the effects of allopurinol on exercise-induced muscle damage. More research is needed to determine whether allopurinol may be useful for preventing not only exertional rhabdomyolysis and acute renal damage but also skeletal muscle wasting in critical illness as well as in immobilized, bedridden, sarcopenic or cachectic patients.

Oxidative damage and neurodegeneration in manganese-induced neurotoxicity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Milatovic, Dejan; Zaja-Milatovic, Snjezana; Gupta, Ramesh C.

2009-10-15

Exposure to excessive manganese (Mn) levels results in neurotoxicity to the extrapyramidal system and the development of Parkinson's disease (PD)-like movement disorder, referred to as manganism. Although the mechanisms by which Mn induces neuronal damage are not well defined, its neurotoxicity appears to be regulated by a number of factors, including oxidative injury, mitochondrial dysfunction and neuroinflammation. To investigate the mechanisms underlying Mn neurotoxicity, we studied the effects of Mn on reactive oxygen species (ROS) formation, changes in high-energy phosphates (HEP), neuroinflammation mediators and associated neuronal dysfunctions both in vitro and in vivo. Primary cortical neuronal cultures showed concentration-dependent alterationsmore » in biomarkers of oxidative damage, F{sub 2}-isoprostanes (F{sub 2}-IsoPs) and mitochondrial dysfunction (ATP), as early as 2 h following Mn exposure. Treatment of neurons with 500 {mu}M Mn also resulted in time-dependent increases in the levels of the inflammatory biomarker, prostaglandin E{sub 2} (PGE{sub 2}). In vivo analyses corroborated these findings, establishing that either a single or three (100 mg/kg, s.c.) Mn injections (days 1, 4 and 7) induced significant increases in F{sub 2}-IsoPs and PGE{sub 2} in adult mouse brain 24 h following the last injection. Quantitative morphometric analyses of Golgi-impregnated striatal sections from mice exposed to single or three Mn injections revealed progressive spine degeneration and dendritic damage of medium spiny neurons (MSNs). These findings suggest that oxidative stress, mitochondrial dysfunction and neuroinflammation are underlying mechanisms in Mn-induced neurodegeneration.« less

DNA Damage Response in Cisplatin-Induced Nephrotoxicity

PubMed Central

Zhu, Shiyao; Pabla, Navjotsingh; Tang, Chengyuan; He, Liyu; Dong, Zheng

2015-01-01

Cisplatin and its derivatives are widely used chemotherapeutic drugs for cancer treatment. However, they have debilitating side-effects in normal tissues and induce ototoxicity, neurotoxicity, and nephrotoxicity. In kidneys, cisplatin preferentially accumulates in renal tubular cells causing tubular cell injury and death, resulting in acute kidney injury (AKI). Recent studies have suggested that DNA damage and the associated DNA damage response (DDR) is an important pathogenic mechanism of AKI following cisplatin treatment. Activation of DDR may lead to cell cycle arrest and DNA repair for cell survival or, in the presence of severe injury, kidney cell death. Modulation of DDR may provide novel renoprotective strategies for cancer patients undergoing cisplatin chemotherapy. PMID:26564230

Ketoconazole-induced testicular damage in rats reduced by Gentiana extract.

PubMed

Amin, Amr

2008-04-01

Ketoconazole (KET) is an antifungal drug with a broad spectrum of activity that also induces reproductive toxicity in humans and animals. The protective effect of Gentiana (GEN) extract (Gentiana lutea) against KET-induced testicular damage was evaluated in male Wistar rats. GEN extract was administered orally (1g/kgbwt/day) for 26 days. Three weeks after extract administration, KET was co-administered intraperitoneally at a dose of 100mg/kg once a day for 5 days. KET-induced reproductive toxicity was associated with clear reductions of the weights of testes and epididymides, sperm indices and serum testosterone levels. KET also induced severe testicular histopathological lesions such as degeneration of the seminiferous tubules and depletion of germ cells. In addition, marked oxidative damage to testicular lipids and alterations of natural antioxidants (catalase (CAT) and superoxide dismutase (SOD)) were reported in association with KET toxicity. Most of the KET-induced effects were greatly decreased with the concomitant application of GEN extract. This study suggests a protective role of GEN extract that could be attributed to its antioxidant properties.

Exercise-induced muscle damage and running economy in humans.

PubMed

Assumpção, Cláudio de Oliveira; Lima, Leonardo Coelho Rabello; Oliveira, Felipe Bruno Dias; Greco, Camila Coelho; Denadai, Benedito Sérgio

2013-01-01

Running economy (RE), defined as the energy demand for a given velocity of submaximal running, has been identified as a critical factor of overall distance running performance. Plyometric and resistance trainings, performed during a relatively short period of time (~15-30 days), have been successfully used to improve RE in trained athletes. However, these exercise types, particularly when they are unaccustomed activities for the individuals, may cause delayed onset muscle soreness, swelling, and reduced muscle strength. Some studies have demonstrated that exercise-induced muscle damage has a negative impact on endurance running performance. Specifically, the muscular damage induced by an acute bout of downhill running has been shown to reduce RE during subsequent moderate and high-intensity exercise (>65% VO₂max). However, strength exercise (i.e., jumps, isoinertial and isokinetic eccentric exercises) seems to impair RE only for subsequent high-intensity exercise (~90% VO₂max). Finally, a single session of resistance exercise or downhill running (i.e., repeated bout effect) attenuates changes in indirect markers of muscle damage and blunts changes in RE.

Carbon Heavy-ion Radiation Induced Biological effects on Oryza sativa L.

NASA Astrophysics Data System (ADS)

Zhang, Meng; Sun, Yeqing; Li, Xishan; Gong, Ning; Meng, Qingmei; Liu, Jiawei; Wang, Ting

2016-07-01

Large number of researches on rice after spaceflights indicated that rice was a favorable model organism to study biological effects induced by space radiation. The stimulative effect could often be found on rice seedlings after irradiation by low-dose energetic heavy-ion radiation. Spaceflight also could induce stimulative effect on kinds of seeds. To further understand the mechanism of low-dose radiation biological effects and the dose range, the germinated rice seeds which were irradiated by different doses of carbon heavy-ion (0, 0.02, 0.1, 0.2, 1, 2, 5, 10, 15 and 20Gy, LET=27.3keV/µm) were used as materials to study. By investigating the variation of rice phenotype under different doses, we found that 2Gy radiation dose was a dividing point of the phenotypic variation. Transmission electron microscopy was used to observe the variation of mitochondria, chloroplast, endoplasmic reticulum, ribosome and nucleus in mesophyll cell of rice apical meristem at 24 hours after radiation with different doses. The cells were not apparently physiologically damaged when the dose of radiation was less than 2Gy. The number of chloroplast did not change significantly, but the number of mitochondria was significantly increased, and gathered around in the chloroplast and endoplasmic reticulum; the obvious lesion of chloroplast and mitochondria were found at the mesophyll cells when radiation dose was higher than 2Gy. The mitochondria were swelling and appearing blurred crest. The chloroplast and mitochondrial mutation rate increased significantly (p<0.01). These phenomena showed that cell biological changes may be the reasons of the stimulation and inhibition effects with the boundary of 2Gy. Since mitochondrial was an important organelle involved in the antioxidative systems, its dysfunction could result in the increase of reactive oxygen species and lipid peroxidation. We found that the growth stimulation induced by low-dose radiation mainly occurred at three-leaf stage along

Stress-induced DNA Damage biomarkers: Applications and limitations

NASA Astrophysics Data System (ADS)

Nikitaki, Zacharenia; Hellweg, Christine; Georgakilas, Alexandros; Ravanat, Jean-Luc

2015-06-01

A variety of environmental stresses like chemicals, UV and ionizing radiation and organism’s endogenous processes like replication stress and metabolism can lead to the generation of reactive oxygen and nitrogen species (ROS/RNS) that can attack cellular vital components like DNA, proteins and lipid membranes. Among them, much attention has been focused on DNA since DNA damages play a role in several biological disorders and aging processes. Thus, DNA damage can be used as a biomarker in a reliable and accurate way to quantify for example radiation exposure and can indicate its possible long term effects and cancer risk. Based on the type of DNA lesions detected one can hypothesize on the most probable mechanisms involved in the formation of these lesions for example in the case of UV and ionizing radiation (e.g. X- or α-, γ-rays, energetic ions, neutrons). In this review we describe the most accepted chemical pathways for DNA damage induction and the different types of DNA lesions, i.e. single, complex DNA lesions etc. that can be used as biomarkers. We critically compare DNA damage detection methods and their limitations. In addition to such DNA damage products, we suggest possible gene inductions that can be used to characterize responses to different types of stresses i.e. radiation, oxidative and replication stress, based on bioinformatic approaches and stringent meta-analysis of literature data.

Ellagic and ferulic acids alleviate gamma radiation and aluminium chloride-induced oxidative damage.

PubMed

Salem, Ahmed M; Mohammaden, Tarek F; Ali, Mohamed A M; Mohamed, Enas A; Hasan, Hesham F

2016-09-01

Ionizing radiation interacts with biological systems through the generation of free radicals, which induce oxidative stress. Aluminium (Al) can negatively impact human health by direct interaction with antioxidant enzymes. Ellagic acid (EA) and Ferulic acid (FA) are plant polyphenolic compounds, have gained attention due to their multiple biological activities. To date, no studies investigating the antioxidant effect of EA/FA in a model involving both γ radiation and aluminium chloride (AlCl3) have been reported. Herein, we investigated the protective effect of EA and FA against oxidative stress induced by γ radiation and AlCl3 in rats. Rats were divided into thirteen groups: a negative control group, 3 positive control groups (γ-irradiated, AlCl3-treated and γ-irradiated+AlCl3-treated) and 9 groups (3 γ-irradiated, 3 AlCl3-treated and 3 γ-irradiated+AlCl3-treated) treated with EA and/or FA. Liver function and lipid profile were assessed. Levels of lipid peroxidation, protein oxidation and endogenous antioxidants as well as the concentrations of copper, iron and zinc were estimated in liver tissue homogenate. Furthermore, liver tissue sections were histologically examined. Oral administration of EA and/or FA resulted in 1) amelioration of AlCl3 and/or γ-radiation-induced hepatic function impairment, dyslipidemia and hepatic histological alterations; 2) reduction in liver MDA and PCC levels; 3) elevation of liver CAT, GPx and SOD activity as well as GSH level; 4) elevation in liver Cu concentrations which was accompanied by a reduction in Fe and Zn concentrations. Oral administration of EA and/or FA may be useful for ameliorating γ radiation and/or AlCl3-induced oxidative damage. Copyright © 2016 Elsevier Inc. All rights reserved.

Comparison of Model Calculations of Biological Damage from Exposure to Heavy Ions with Measurements

NASA Technical Reports Server (NTRS)

Kim, Myung-Hee Y.; Hada, Megumi; Cucinotta, Francis A.; Wu, Honglu

2014-01-01

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. Dose delivered by the charged particle increases sharply at 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. Measurements of the induction of micronuclei (MN) have made 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. Although the data did not reveal an increased yield of MN at the location of the Bragg peak, the increased inhibition of cell progression, which is related to cell death, was found at the Bragg peak location. These results are compared to the calculations of biological damage using a stochastic Monte-Carlo track structure model, Galactic Cosmic Ray Event-based Risk Model (GERM) code (Cucinotta, et al., 2011). The GERM code estimates the basic physical properties along the passage of heavy ions in tissue and shielding materials, by which the experimental set-up can be interpreted. The code can also be used to describe the biophysical events of interest in radiobiology, cancer therapy, and space exploration. The calculation has shown that the severely damaged cells at the Bragg peak are more likely to go through reproductive death, the so called "overkill".

Impact of storage induced outgassing organic contamination on laser induced damage of silica optics at 351 nm.

PubMed

Bien-Aimé, K; Belin, C; Gallais, L; Grua, P; Fargin, E; Néauport, J; Tovena-Pecault, I

2009-10-12

The impact of storage conditions on laser induced damage density at 351 nm on bare fused polished silica samples has been studied. Intentionally outgassing of polypropylene pieces on silica samples was done. We evidenced an important increase of laser induced damage density on contaminated samples demonstrating that storage could limit optics lifetime performances. Atomic Force Microscopy (AFM) and Gas Chromatography -Mass Spectrometry (GC-MS) have been used to identify the potential causes of this effect. It shows that a small quantity of organic contamination deposited on silica surface is responsible for this degradation. Various hypotheses are proposed to explain the damage mechanism. The more likely hypothesis is a coupling between surface defects of optics and organic contaminants.

Dunnione ameliorates cisplatin-induced small intestinal damage by modulating NAD{sup +} metabolism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pandit, Arpana; Kim, Hyung-Jin; Oh, Gi-Su

2015-11-27

Although cisplatin is a widely used anticancer drug for the treatment of a variety of tumors, its use is critically limited because of adverse effects such as ototoxicity, nephrotoxicity, neuropathy, and gastrointestinal damage. Cisplatin treatment increases oxidative stress biomarkers in the small intestine, which may induce apoptosis of epithelial cells and thereby elicit damage to the small intestine. Nicotinamide adenine dinucleotide (NAD{sup +}) is a cofactor for various enzymes associated with cellular homeostasis. In the present study, we demonstrated that the hyper-activation of poly(ADP-ribose) polymerase-1 (PARP-1) is closely associated with the depletion of NAD{sup +} in the small intestine aftermore » cisplatin treatment, which results in downregulation of sirtuin1 (SIRT1) activity. Furthermore, a decrease in SIRT1 activity was found to play an important role in cisplatin-mediated small intestinal damage through nuclear factor (NF)-κB p65 activation, facilitated by its acetylation increase. However, use of dunnione as a strong substrate for the NADH:quinone oxidoreductase 1 (NQO1) enzyme led to an increase in intracellular NAD{sup +} levels and prevented the cisplatin-induced small intestinal damage correlating with the modulation of PARP-1, SIRT1, and NF-κB. These results suggest that direct modulation of cellular NAD{sup +} levels by pharmacological NQO1 substrates could be a promising therapeutic approach for protecting against cisplatin-induced small intestinal damage. - Highlights: • NAD{sup +} acts as a cofactor for numerous enzymes including Sirtuins and PARP. • Up-regulation of SIRT1 could attenuate the cisplatin-induced intestinal damage. • Modulation of the cellular NAD{sup +} could be a promising therapeutic approach.« less

Gold nanoparticles induce DNA damage in the blood and liver of rats

NASA Astrophysics Data System (ADS)

Cardoso, Eria; Londero, Eduardo; Ferreira, Gabriela Kozuchovski; Rezin, Gislaine Tezza; Zanoni, Elton Torres; de Souza Notoya, Frederico; Leffa, Daniela Dimer; Damiani, Adriani Paganini; Daumann, Francine; Rohr, Paula; da Silva, Luciano; Andrade, Vanessa M.; da Silva Paula, Marcos Marques

2014-11-01

The potential of gold nanoparticles (GNPs) for use in different biological applications has led to a strong interest in the study of their possible deleterious effects in biological systems and how these effects may be mitigated. This study was undertaken to investigate the effects of the acute and chronic administration of GNPs with mean diameters of 10 and 30 nm on deoxyribonucleic acid (DNA) damage in the blood and liver of adult rats. For the acute administration, Wistar adult rats received a single intraperitoneal injection of either GNPs or a saline solution. For the chronic administration, Wistar adult rats received a daily single injection of the same GNPs or saline solution for 28 days. Twenty-four hours after either the single (acute) or final injection (chronic), the rats were euthanised by decapitation, and the blood and liver were isolated for the evaluation of DNA damage. In this study, we demonstrated that the acute and chronic administration of GNPs 10 and 30 nm in size increased the frequency of DNA damage and the damage index in the blood and liver of adult rats. These findings suggest that the DNA damage may be caused by oxidative stress, which occurred regardless of the type of administration and GNP size.

Mechanisms for microvascular damage induced by ultrasound-activated microbubbles

NASA Astrophysics Data System (ADS)

Chen, Hong; Brayman, Andrew A.; Evan, Andrew P.; Matula, Thomas J.

2012-10-01

To provide insight into the mechanisms of microvascular damage induced by ultrasound-activated microbubbles, experimental studies were performed to correlate microvascular damage to the dynamics of bubble-vessel interactions. High-speed photomicrography was used to record single microbubbles interacting with microvessels in ex vivo tissue, under the exposure of short ultrasound pulses with a center frequency of 1 MHz and peak negative pressures (PNP) ranging from 0.8-4 MPa. Vascular damage associated with observed bubble-vessel interactions was either indicated directly by microbubble extravasation or examined by transmission electron microscopy (TEM) analyses. As observed previously, the high-speed images revealed that ultrasound-activated microbubbles could cause distention and invagination of adjacent vessel walls, and could form liquid jets in microvessels. Vessel distention, invagination, and liquid jets were associated with the damage of microvessels whose diameters were smaller than those of maximally expanded microbubbles. However, vessel invagination appeared to be the dominant mechanism for the damage of relative large microvessels.

Mechanisms for microvascular damage induced by ultrasound-activated microbubbles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen Hong; Brayman, Andrew A.; Evan, Andrew P.

To provide insight into the mechanisms of microvascular damage induced by ultrasound-activated microbubbles, experimental studies were performed to correlate microvascular damage to the dynamics of bubble-vessel interactions. High-speed photomicrography was used to record single microbubbles interacting with microvessels in ex vivo tissue, under the exposure of short ultrasound pulses with a center frequency of 1 MHz and peak negative pressures (PNP) ranging from 0.8-4 MPa. Vascular damage associated with observed bubble-vessel interactions was either indicated directly by microbubble extravasation or examined by transmission electron microscopy (TEM) analyses. As observed previously, the high-speed images revealed that ultrasound-activated microbubbles could cause distentionmore » and invagination of adjacent vessel walls, and could form liquid jets in microvessels. Vessel distention, invagination, and liquid jets were associated with the damage of microvessels whose diameters were smaller than those of maximally expanded microbubbles. However, vessel invagination appeared to be the dominant mechanism for the damage of relative large microvessels.« less

Few-cycle pulse laser induced damage threshold determination of ultra-broadband optics.

PubMed

Kafka, Kyle R P; Talisa, Noah; Tempea, Gabriel; Austin, Drake R; Neacsu, Catalin; Chowdhury, Enam A

2016-12-12

A systematic study of few-cycle pulse laser induced damage threshold (LIDT) determination was performed for commercially-available ultra-broadband optics, (i.e. chirped mirrors, silver mirrors, beamsplitters, etc.) in vacuum and in air, for single and multi-pulse regime (S-on-1). Multi-pulse damage morphology at fluences below the single-pulse LIDT was studied in order to investigate the mechanisms leading to the onset of damage. Stark morphological contrast was observed between multi-pulse damage sites formed in air versus those in vacuum. One effect of vacuum testing compared to air included suppression of laser-induced periodic surface structures (LIPSS) formation, possibly influenced by a reduced presence of damage debris. Another effect of vacuum was occasional lowering of LIDT, which appears to be due to the stress-strain performance of the coating design during laser irradiation and under the external stress of vacuum ambience. A fused silica substrate is also examined, and a non-LIPSS nanostructuring is observed on the surface. Possible mechanisms are discussed.

Robust optimization of the laser induced damage threshold of dielectric mirrors for high power lasers.

PubMed

Chorel, Marine; Lanternier, Thomas; Lavastre, Éric; Bonod, Nicolas; Bousquet, Bruno; Néauport, Jérôme

2018-04-30

We report on a numerical optimization of the laser induced damage threshold of multi-dielectric high reflection mirrors in the sub-picosecond regime. We highlight the interplay between the electric field distribution, refractive index and intrinsic laser induced damage threshold of the materials on the overall laser induced damage threshold (LIDT) of the multilayer. We describe an optimization method of the multilayer that minimizes the field enhancement in high refractive index materials while preserving a near perfect reflectivity. This method yields a significant improvement of the damage resistance since a maximum increase of 40% can be achieved on the overall LIDT of the multilayer.

Neuronal growth cones respond to laser-induced axonal damage

PubMed Central

Wu, Tao; Mohanty, Samarendra; Gomez-Godinez, Veronica; Shi, Linda Z.; Liaw, Lih-Huei; Miotke, Jill; Meyer, Ronald L.; Berns, Michael W.

2012-01-01

Although it is well known that damage to neurons results in release of substances that inhibit axonal growth, release of chemical signals from damaged axons that attract axon growth cones has not been observed. In this study, a 532 nm 12 ns laser was focused to a diffraction-limited spot to produce site-specific damage to single goldfish axons in vitro. The axons underwent a localized decrease in thickness (‘thinning’) within seconds. Analysis by fluorescence and transmission electron microscopy indicated that there was no gross rupture of the cell membrane. Mitochondrial transport along the axonal cytoskeleton immediately stopped at the damage site, but recovered over several minutes. Within seconds of damage nearby growth cones extended filopodia towards the injury and were often observed to contact the damaged site. Turning of the growth cone towards the injured axon also was observed. Repair of the laser-induced damage was evidenced by recovery of the axon thickness as well as restoration of mitochondrial movement. We describe a new process of growth cone response to damaged axons. This has been possible through the interface of optics (laser subcellular surgery), fluorescence and electron microscopy, and a goldfish retinal ganglion cell culture model. PMID:21831892

Laser-induced retinal damage thresholds for annular retinal beam profiles

NASA Astrophysics Data System (ADS)

Kennedy, Paul K.; Zuclich, Joseph A.; Lund, David J.; Edsall, Peter R.; Till, Stephen; Stuck, Bruce E.; Hollins, Richard C.

2004-07-01

The dependence of retinal damage thresholds on laser spot size, for annular retinal beam profiles, was measured in vivo for 3 μs, 590 nm pulses from a flashlamp-pumped dye laser. Minimum Visible Lesion (MVL)ED50 thresholds in rhesus were measured for annular retinal beam profiles covering 5, 10, and 20 mrad of visual field; which correspond to outer beam diameters of roughly 70, 160, and 300 μm, respectively, on the primate retina. Annular beam profiles at the retinal plane were achieved using a telescopic imaging system, with the focal properties of the eye represented as an equivalent thin lens, and all annular beam profiles had a 37% central obscuration. As a check on experimental data, theoretical MVL-ED50 thresholds for annular beam exposures were calculated using the Thompson-Gerstman granular model of laser-induced thermal damage to the retina. Threshold calculations were performed for the three experimental beam diameters and for an intermediate case with an outer beam diameter of 230 μm. Results indicate that the threshold vs. spot size trends, for annular beams, are similar to the trends for top hat beams determined in a previous study; i.e., the threshold dose varies with the retinal image area for larger image sizes. The model correctly predicts the threshold vs. spot size trends seen in the biological data, for both annular and top hat retinal beam profiles.

Ku70 inhibits gemcitabine-induced DNA damage and pancreatic cancer cell apoptosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ma, Jiali; Hui, Pingping; Meng, Wenying

The current study focused on the role of Ku70, a DNA-dependent protein kinase (DNA-PK) complex protein, in pancreatic cancer cell resistance to gemcitabine. In both established cell lines (Mia-PaCa-2 and PANC-1) and primary human pancreatic cancer cells, shRNA/siRNA-mediated knockdown of Ku70 significantly sensitized gemcitabine-induced cell death and proliferation inhibition. Meanwhile, gemcitabine-induced DNA damage and subsequent pancreatic cancer cell apoptosis were also potentiated with Ku70 knockdown. On the other hand, exogenous overexpression of Ku70 in Mia-PaCa-2 cells suppressed gemcitabine-induced DNA damage and subsequent cell apoptosis. In a severe combined immune deficient (SCID) mice Mia-PaCa-2 xenograft model, gemcitabine-induced anti-tumor activity was remarkably pontificatedmore » when combined with Ku70 shRNA knockdown in the xenografts. The results of this preclinical study imply that Ku70 might be a primary resistance factor of gemcitabine, and Ku70 silence could significantly chemo-sensitize gemcitabine in pancreatic cancer cells. - Highlights: • Ku70 knockdown sensitizes gemcitabine-induced killing of pancreatic cancer cells. • Ku70 knockdown facilitates gemcitabine-induced DNA damage and cell apoptosis. • Ku70 overexpression deceases gemcitabine's sensitivity in pancreatic cancer cells. • Ku70 knockdown sensitizes gemcitabine-induced anti-tumor activity in vivo.« less

Radiation damage to macromolecules: kill or cure?

PubMed

Garman, Elspeth F; Weik, Martin

2015-03-01

Radiation damage induced by X-ray beams during macromolecular diffraction experiments remains an issue of concern in structural biology. While advances in our understanding of this phenomenon, driven in part by a series of workshops in this area, undoubtedly have been and are still being made, there are still questions to be answered. Eight papers in this volume give a flavour of ongoing investigations, addressing various issues. These range over: a proposed new metric derived from atomic B-factors for identifying potentially damaged amino acid residues, a study of the relative damage susceptibility of protein and DNA in a DNA/protein complex, a report of an indication of specific radiation damage to a protein determined from data collected using an X-ray free-electron laser (FEL), an account of the challenges in FEL raw diffraction data analysis, an exploration of the possibilities of using radiation damage induced phasing to solve structures using FELs, simulations of radiation damage as a function of FEL temporal pulse profiles, results on the influence of radiation damage during scanning X-ray diffraction measurements and, lastly, consideration of strategies for minimizing radiation damage during SAXS experiments. In this short introduction, these contributions are briefly placed in the context of other current work on radiation damage in the field.

Hardening measures for bipolar transistors against microwave-induced damage

NASA Astrophysics Data System (ADS)

Chai, Chang-Chun; Ma, Zhen-Yang; Ren, Xing-Rong; Yang, Yin-Tang; Zhao, Ying-Bo; Yu, Xin-Hai

2013-06-01

In the present paper we study the influences of the bias voltage and the external components on the damage progress of a bipolar transistor induced by high-power microwaves. The mechanism is presented by analyzing the variation in the internal distribution of the temperature in the device. The findings show that the device becomes less vulnerable to damage with an increase in bias voltage. Both the series diode at the base and the relatively low series resistance at the emitter, Re, can obviously prolong the burnout time of the device. However, Re will aid damage to the device when the value is sufficiently high due to the fact that the highest hot spot shifts from the base-emitter junction to the base region. Moreover, the series resistance at the base Rb will weaken the capability of the device to withstand microwave damage.

Oxidative DNA damage induced by a hydroperoxide derivative of cyclophosphamide.

PubMed

Murata, Mariko; Suzuki, Toshinari; Midorikawa, Kaoru; Oikawa, Shinji; Kawanishi, Shosuke

2004-09-15

Interstrand DNA cross-linking has been considered to be the primary action mechanism of cyclophosphamide (CP) and its hydroperoxide derivative, 4-hydroperoxycyclophosphamide (4-HC). To clarify the mechanism of anti-tumor effects by 4-HC, we investigated DNA damage in a human leukemia cell line, HL-60, and its H(2)O(2)-resistant clone HP100. Apoptosis DNA ladder formation was detected in HL-60 cells treated with 4-HC, whereas it was not observed in HP100 cells. 4-HC significantly increased 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) formation, a marker of oxidative DNA damage, in HL-60 cells. On the other hand, CP did not significantly induce 8-oxodG formation and apoptosis in HL-60 cells under the same conditions as did 4-HC. Using (32)P-labeled DNA fragments from the human p53 tumor suppressor gene, 4-HC was found to cause Cu(II)-mediated oxidative DNA damage, but CP did not. Catalase inhibited 4-HC-induced DNA damage, including 8-oxodG formation, suggesting the involvement of H(2)O(2). The generation of H(2)O(2) during 4-HC degradation was ascertained by procedures using scopoletin and potassium iodide. We conclude that, in addition to DNA cross-linking, oxidative DNA damage through H(2)O(2) generation may participate in the anti-tumor effects of 4-HC.

Modelling biofilm-induced formation damage and biocide treatment in subsurface geosystems

PubMed Central

Ezeuko, C C; Sen, A; Gates, I D

2013-01-01

Biofilm growth in subsurface porous media, and its treatment with biocides (antimicrobial agents), involves a complex interaction of biogeochemical processes which provide non-trivial mathematical modelling challenges. Although there are literature reports of mathematical models to evaluate biofilm tolerance to biocides, none of these models have investigated biocide treatment of biofilms growing in interconnected porous media with flow. In this paper, we present a numerical investigation using a pore network model of biofilm growth, formation damage and biocide treatment. The model includes three phases (aqueous, adsorbed biofilm, and solid matrix), a single growth-limiting nutrient and a single biocide dissolved in the water. Biofilm is assumed to contain a single species of microbe, in which each cell can be a viable persister, a viable non-persister, or non-viable (dead). Persisters describe small subpopulation of cells which are tolerant to biocide treatment. Biofilm tolerance to biocide treatment is regulated by persister cells and includes ‘innate’ and ‘biocide-induced’ factors. Simulations demonstrate that biofilm tolerance to biocides can increase with biofilm maturity, and that biocide treatment alone does not reverse biofilm-induced formation damage. Also, a successful application of biological permeability conformance treatment involving geologic layers with flow communication is more complicated than simply engineering the attachment of biofilm-forming cells at desired sites. PMID:23164434

Carbon monoxide-induced suspended animation protects against hypoxic damage in Caenorhabditis elegans

PubMed Central

Nystul, Todd G.; Roth, Mark B.

2004-01-01

Oxygen deprivation is a major cause of cellular damage and death. Here we demonstrate that Caenorhabditis elegans embryos, which can survive both in anoxia (<0.001 kPa O2) by entering into suspended animation and in mild hypoxia (0.25-1 kPa O2) through a hypoxia-inducible factor 1-mediated response, cannot survive in intermediate concentrations of oxygen, between 0.01 and 0.1 kPa O2. Moreover, we show that carbon monoxide can protect C. elegans embryos against hypoxic damage in this sensitive range. Carbon monoxide can also rescue the hypoxia-sensitive mutant hif-1(ia04) from lethality in hypoxia. This work defines the oxygen tensions over which hypoxic damage occurs in C. elegans embryos and demonstrates that carbon monoxide can prevent this damage by inducing suspended animation. PMID:15184665

Endoplasmic Reticulum Stress Mediates Methamphetamine-Induced Blood–Brain Barrier Damage

PubMed Central

Qie, Xiaojuan; Wen, Di; Guo, Hongyan; Xu, Guanjie; Liu, Shuai; Shen, Qianchao; Liu, Yi; Zhang, Wenfang; Cong, Bin; Ma, Chunling

2017-01-01

Methamphetamine (METH) abuse causes serious health problems worldwide, and long-term use of METH disrupts the blood–brain barrier (BBB). Herein, we explored the potential mechanism of endoplasmic reticulum (ER) stress in METH-induced BBB endothelial cell damage in vitro and the therapeutic potential of endoplasmic reticulum stress inhibitors for METH-induced BBB disruption in C57BL/6J mice. Exposure of immortalized BMVEC (bEnd.3) cells to METH significantly decreased cell viability, induced apoptosis, and diminished the tightness of cell monolayers. METH activated ER stress sensor proteins, including PERK, ATF6, and IRE1, and upregulated the pro-apoptotic protein CHOP. The ER stress inhibitors significantly blocked the upregulation of CHOP. Knockdown of CHOP protected bEnd.3 cells from METH-induced cytotoxicity. Furthermore, METH elevated the production of reactive oxygen species (ROS) and induced the dysfunction of mitochondrial characterized by a Bcl2/Bax ratio decrease, mitochondrial membrane potential collapse, and cytochrome c. ER stress release was partially reversed by ROS inhibition, and cytochrome c release was partially blocked by knockdown of CHOP. Finally, PBA significantly attenuated METH-induced sodium fluorescein (NaFluo) and Evans Blue leakage, as well as tight junction protein loss, in C57BL/6J mice. These data suggest that BBB endothelial cell damage was caused by METH-induced endoplasmic reticulum stress, which further induced mitochondrial dysfunction, and that PBA was an effective treatment for METH-induced BBB disruption. PMID:28959203

Damage-induced ectopic recombination in the yeast Saccharomyces cerevisiae.

PubMed

Kupiec, M; Steinlauf, R

1997-06-09

Mitotic recombination in the yeast Saccharomyces cerevisiae is induced when cells are irradiated with UV or X-rays, reflecting the efficient repair of damage by recombinational repair mechanisms. We have used multiply marked haploid strains that allow the simultaneous detection of several types of ectopic recombination events. We show that inter-chromosomal ectopic conversion of lys2 heteroalleles and, to a lesser extent, direct repeat recombination (DRR) between non-tandem repeats, are increased by DNA-damaging agents; in contrast, ectopic recombination of the naturally occurring Ty element is not induced. We have tested several hypotheses that could explain the preferential lack of induction of Ty recombination by DNA-damaging agents. We have found that the lack of induction cannot be explained by a cell cycle control or by an effect of the mating-type genes. We also found no role for the flanking long terminal repeats (LTRs) of the Ty in preventing the induction. Ectopic conversion, DRR, and forward mutation of artificial repeats show different kinetics of induction at various positions of the cell cycle, reflecting different mechanisms of recombination. We discuss the mechanistic and evolutionary aspects of these results.

Morphological studies of laser-induced photoacoustic damage

NASA Astrophysics Data System (ADS)

Flotte, Thomas J.; Yashima, Yutaka; Watanabe, Shinichi; McAuliffe, Daniel J., Sr.; Jacques, Steven L.

1990-06-01

Argon-fluoride excimer laser ablation of stratum comeum causes deeper tissue damage than expected for thermal or photochemical mechanisms, suggesting thatphotoacoustic waves have arole in tissue damage. Laserirradiation (193 nm, 14 ns pulses, 1-2 Hz) attworadiantexposures, 60 and 160 mJ/cm2perpulse was usedto ablate the stratumcomeumofskin. Light and electron microscopy ofimmediate biopsies demonstrated damage to fibroblasts as deep as 88 and 220 jun, respectively, below the ablation site. Ablation throughwaterwas usedtoinertially confine the ablation zone. Partial ablationofs.c. through airproducedno damage, whereas partial ablation through water damaged skin to amean depth of 1 14.5 8.8( Full thickness ablation of s.c. through air and water produced damage zones measuring 192.2 16.2 and 293.0 71.6 rim, respectively (p <0.05). The increased depth ofdamage in the presence ofinertial confinementprovided by the layer of water strongly supports a photoacoustic mechanism ofdamage. The depths ofdamage for thelarge spot, line, and small spots were 43 1 164 urn, 269 96xni, andno damage. The spot size dependence ofthedepthofdamage is consistentwiththe geometric attenuation one would expect to be present from a pressure wave related phenomena. Sequential biopsies were taken over a 7 day period for light and transmission electron microscopy. At 24 hours, there was necrosis of the epidermis and papillary dermis subjacent to the ablation site, with neutrophils surrounding and demarcating the affected area. The necrotic zone sloughedby48 hours. Thereepithelializationwas completeby7 days. The sequenceofrepairis similartoknife wound healing which we have previously studied, and is analogous to other wound healing processes. We have used an experimental model of ArF excimer laser ablation of stratum corneum to investigate laser-induced photoacoustic damage. The evidence for the injury being due to pressure transients is indirectbutcompelling. Whether these pressuretransients are

ATM-activated autotaxin (ATX) propagates inflammation and DNA damage in lung epithelial cells: a new mode of action for silica-induced DNA damage?

PubMed

Zheng, Huiyuan; Högberg, Johan; Stenius, Ulla

2017-12-07

Silica exposure is a common risk factor for lung cancer. It has been claimed that key elements in cancer development are activation of inflammatory cells that indirectly induce DNA damage and proliferative stimuli in respiratory epithelial cells. We studied DNA damage induced by silica particles in respiratory epithelial cells and focused the role of the signaling enzyme autotaxin (ATX). A549 and 16 bronchial epithelial cells (16HBE) lung epithelial cells were exposed to silica particles. Reactive oxygen species (ROS), NOD-like receptor family pyrin domain containing-3 (NLRP3) inflammasome activation, ATX, ataxia telangiectasia mutated (ATM), and DNA damage (γH2AX, pCHK1, pCHK2, comet assay) were end points. Low doses of silica induced NLRP3 activation, DNA damage accumulation, and ATM phosphorylation. A novel finding was that ATM induced ATX generation and secretion. Not only silica but also rotenone, camptothecin and H2O2 activated ATX via ATM, suggesting that ATX is part of a generalized ATM response to double-strand breaks (DSBs). Surprisingly, ATX inhibition mitigated DNA damage accumulation at later time points (6-16 h), and ATX transfection caused NLRP3 activation and DNA damage. Furthermore, the product of ATX enzymatic activity, lysophosphatidic acid, recapitulated the effects of ATX transfection. These data indicate an ATM-ATX-dependent loop that propagates inflammation and DSB accumulation, making low doses of silica effective inducers of DSBs in epithelial cells. We conclude that an ATM-ATX axis interconnects DSBs with silica-induced inflammation and propagates these effects in epithelial cells. Further studies of this adverse outcome pathway may give an accurate assessment of the lowest doses of silica that causes cancer. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Evaluation of a contraction flow field on hydrodynamic damage to entomopathogenic nematodes-A biological pest control agent.

PubMed

Fife, Jane P; Derksen, Richard C; Ozkan, H Erdal; Grewal, Parwinder S; Chalmers, Jeffrey J; Krause, Charles R

2004-04-05

Mechanized production and delivery of biological pesticides presents challenges because the biological agents must remain viable during these processes. This study evaluates the effect of flow through an abrupt contraction, where flow characteristics similar to that found within bioprocesses and spray equipment are developed, on damage to a benchmark biological pest control agent, entomopathogenic nematodes (EPNs). An opposed-pistons, contraction flow device generated volumetric flow rates ranging between 8.26 cm(3)/s and 41.3 cm(3)/s. Four EPN species were evaluated: Heterorhabditis bacteriophora, Heterorhabditis megidis, Steinernema carpocapsae, and Steinernema glaseri. Damage was quantified by counting living and dead EPNs. Optical and cold field emission scanning electron microscope (CFE-SEM) images provided qualitative information to describe how the damage occurred. The experimental flow field was completely described using FLUENT, a computational fluid dynamics program. Local flow parameters computed in FLUENT were compared to EPN damage. The type and extent of damage varied between EPN species. Damaged Heterorhabditis spp. generally remained whole with an internal rupture located near the center of the body, while Steinernema spp. most often broke into several pieces. The fast-transient stress field generated at the entrance to the contraction caused a momentary tensile loading and then relaxation that damaged the EPNs. At high flow rates, the tensile stresses became large enough to cause failure of the EPN structural membrane. The relative elasticity of the EPN structural membrane may explain the differences in damage observed between the species. It is speculated that the internal rupture of the Heterorhabditis spp. occurred during the processes of stretching and relaxing at the contraction entrance. Appreciable damage was observed at lower average energy dissipation rates for H. bacteriophora (1.23E + 8 W/m(3)), H. megidis (1.72E + 8 W/m(3)), and S

Nano-ranged low-energy ion-beam-induced DNA transfer in biological cells

NASA Astrophysics Data System (ADS)

Yu, L. D.; Wongkham, W.; Prakrajang, K.; Sangwijit, K.; Inthanon, K.; Thongkumkoon, P.; Wanichapichart, P.; Anuntalabhochai, S.

2013-06-01

Low-energy ion beams at a few tens of keV were demonstrated to be able to induce exogenous macromolecules to transfer into plant and bacterial cells. In the process, the ion beam with well controlled energy and fluence bombarded living cells to cause certain degree damage in the cell envelope in nanoscales to facilitate the macromolecules such as DNA to pass through the cell envelope and enter the cell. Consequently, the technique was applied for manipulating positive improvements in the biological species. This physical DNA transfer method was highly efficient and had less risk of side-effects compared with chemical and biological methods. For better understanding of mechanisms involved in the process, a systematic study on the mechanisms was carried out. Applications of the technique were also expanded from DNA transfer in plant and bacterial cells to DNA transfection in human cancer cells potentially for the stem cell therapy purpose. Low-energy nitrogen and argon ion beams that were applied in our experiments had ranges of 100 nm or less in the cell envelope membrane which was majorly composed of polymeric cellulose. The ion beam bombardment caused chain-scission dominant damage in the polymer and electrical property changes such as increase in the impedance in the envelope membrane. These nano-modifications of the cell envelope eventually enhanced the permeability of the envelope membrane to favor the DNA transfer. The paper reports details of our research in this direction.

Modulation of DNA-Induced Damage and Repair Capacity in Humans after Dietary Intervention with Lutein-Enriched Fermented Milk

PubMed Central

Herrero-Barbudo, Carmen; Soldevilla, Beatriz; Pérez-Sacristán, Belén; Blanco-Navarro, Inmaculada; Herrera, Mercedes; Granado-Lorencio, Fernando; Domínguez, Gemma

2013-01-01

Dietary factors provide protection against several forms of DNA damage. Additionally, consumer demand for natural products favours the development of bioactive food ingredients with health benefits. Lutein is a promising biologically active component in the food industry. The EFSA Panel on Dietetic Products, Nutrition and Allergies considers that protection from oxidative damage may be a beneficial physiological effect but that a cause and effect relationship has not been established. Thus, our aim was to evaluate the safety and potential functional effect of a lutein-enriched milk product using the Comet Assay in order to analyze the baseline, the induced DNA-damage and the repair capacity in the lymphocytes of 10 healthy donors before and after the intake of the mentioned product. Our data suggest that the regular consumption of lutein-enriched fermented milk results in a significant increase in serum lutein levels and this change is associated with an improvement in the resistance of DNA to damage and the capacity of DNA repair in lymphocytes. Our results also support the lack of a genotoxic effect at the doses supplied as well as the absence of interactions and side effects on other nutritional and biochemicals markers. PMID:24040187

Feasibility of OCT to detect radiation-induced esophageal damage in small animal models (Conference Presentation)

NASA Astrophysics Data System (ADS)

Jelvehgaran, Pouya; Alderliesten, Tanja; Salguero, Javier; Borst, Gerben; Song, Ji-Ying; van Leeuwen, Ton G.; de Boer, Johannes F.; de Bruin, Daniel M.; van Herk, Marcel B.

2016-03-01

Lung cancer survival is poor and radiotherapy patients often suffer serious treatment side effects. The esophagus is particularly sensitive leading to reduced food intake or even fistula formation. Only few direct techniques exist to measure radiation-induced esophageal damage, for which knowledge is needed to improve the balance between risk of tumor recurrence and complications. Optical coherence tomography (OCT) is a minimally-invasive imaging technique that obtains cross-sectional, high-resolution (1-10µm) images and is capable of scanning the esophageal wall up to 2-3mm depth. In this study we investigated the feasibility of OCT to detect esophageal radiation damage in mice. In total 30 mice were included in 4 study groups (1 main and 3 control groups). Mice underwent cone-beam CT imaging for initial setup assessment and dose planning followed by single-fraction dose delivery of 4, 10, 16, and 20Gy on 5mm spots, spaced 10mm apart. Mice were repeatedly imaged using OCT: pre-irradiation and up to 3 months post-irradiation. The control groups received either OCT only, irradiation only, or were sham-operated. We used histopathology as gold standard for radiation-induced damage diagnosis. The study showed edema in both the main and OCT-only groups. Furthermore, radiation-induced damage was primarily found in the highest dose region (distal esophagus). Based on the histopathology reports we were able to identify the radiation-induced damage in the OCT images as a change in tissue scattering related to the type of induced damage. This finding indicates the feasibility and thereby the potentially promising role of OCT in radiation-induced esophageal damage assessment.

Aag DNA Glycosylase Promotes Alkylation-Induced Tissue Damage Mediated by Parp1

PubMed Central

Calvo, Jennifer A.; Moroski-Erkul, Catherine A.; Lake, Annabelle; Eichinger, Lindsey W.; Shah, Dharini; Jhun, Iny; Limsirichai, Prajit; Bronson, Roderick T.; Christiani, David C.; Meira, Lisiane B.; Samson, Leona D.

2013-01-01

Alkylating agents comprise a major class of front-line cancer chemotherapeutic compounds, and while these agents effectively kill tumor cells, they also damage healthy tissues. Although base excision repair (BER) is essential in repairing DNA alkylation damage, under certain conditions, initiation of BER can be detrimental. Here we illustrate that the alkyladenine DNA glycosylase (AAG) mediates alkylation-induced tissue damage and whole-animal lethality following exposure to alkylating agents. Aag-dependent tissue damage, as observed in cerebellar granule cells, splenocytes, thymocytes, bone marrow cells, pancreatic β-cells, and retinal photoreceptor cells, was detected in wild-type mice, exacerbated in Aag transgenic mice, and completely suppressed in Aag −/− mice. Additional genetic experiments dissected the effects of modulating both BER and Parp1 on alkylation sensitivity in mice and determined that Aag acts upstream of Parp1 in alkylation-induced tissue damage; in fact, cytotoxicity in WT and Aag transgenic mice was abrogated in the absence of Parp1. These results provide in vivo evidence that Aag-initiated BER may play a critical role in determining the side-effects of alkylating agent chemotherapies and that Parp1 plays a crucial role in Aag-mediated tissue damage. PMID:23593019

Eugenia dysenterica DC. (Myrtaceae) exerts chemopreventive effects against hexavalent chromium-induced damage in vitro and in vivo.

PubMed

Ávila, Renato Ivan de; Mattos Alvarenga, Cátia Belo; Ávila, Paulo Henrique Marcelino de; Moreira, Roger Cardoso; Arruda, Andréa Fernandes; Fernandes, Thaís de Oliveira; Rodrigues, Bruna Dos Santos; Andrade, Wanessa Machado; Batista, Aline Carvalho; Paula, José Realino de; Valadares, Marize Campos

2016-11-01

Eugenia dysenterica DC. (Myrtaceae) has been widely used in the folk medicine and it presents phytochemicals constituents associated to antioxidant properties. The objective of this study was to investigate the protective effects of E. dysenterica leaf hydroalcoholic extract (EDE) in vitro and in vivo using AMJ2-C11 cells and Swiss mice exposed to hexavalent chromium [Cr(VI)], respectively. AMJ2-C11 cells were pretreated with EDE and exposed to Cr(VI) to evaluate cytotoxicity and the pathways involved in the chemopreventive effects of the extract. Mice were daily pretreated with EDE and then exposed to Cr(VI). Survival analysis, histopathological examination and determination of Cr levels in biological tissues were carried out. In vitro studies showed that pretreatment of the AMJ2-C11 cells with EDE protected against the cytotoxicity and oxidative stress induced by Cr(VI). Consequently, the pretreatment with EDE reduced reactive oxygen species and apoptosis triggered by Cr(VI), probably by a marked antioxidant and chelating activities demonstrated by EDE. Regarding in vivo studies, pretreatment for 10 days with EDE increased survival of the mice exposed to Cr(VI). In addition, EDE prevented liver and kidney pathological damages, in parallel with reduction in chromium levels found in these organs and plasma. EDE also showed a marked antioxidant potential associated with the presence of polyphenols, especially flavonoids and tannins, as confirmed by HPLC-PDA. The study showed that EDE protects against Cr(VI)-induced damage in vitro and in vivo supporting further studies for the development of therapeutic products applied to prevent the damage induced by toxic metals, especially Cr(VI).

The sequence specificity of UV-induced DNA damage in a systematically altered DNA sequence.

PubMed

Khoe, Clairine V; Chung, Long H; Murray, Vincent

2018-06-01

The sequence specificity of UV-induced DNA damage was investigated in a specifically designed DNA plasmid using two procedures: end-labelling and linear amplification. Absorption of UV photons by DNA leads to dimerisation of pyrimidine bases and produces two major photoproducts, cyclobutane pyrimidine dimers (CPDs) and pyrimidine(6-4)pyrimidone photoproducts (6-4PPs). A previous study had determined that two hexanucleotide sequences, 5'-GCTC*AC and 5'-TATT*AA, were high intensity UV-induced DNA damage sites. The UV clone plasmid was constructed by systematically altering each nucleotide of these two hexanucleotide sequences. One of the main goals of this study was to determine the influence of single nucleotide alterations on the intensity of UV-induced DNA damage. The sequence 5'-GCTC*AC was designed to examine the sequence specificity of 6-4PPs and the highest intensity 6-4PP damage sites were found at 5'-GTTC*CC nucleotides. The sequence 5'-TATT*AA was devised to investigate the sequence specificity of CPDs and the highest intensity CPD damage sites were found at 5'-TTTT*CG nucleotides. It was proposed that the tetranucleotide DNA sequence, 5'-YTC*Y (where Y is T or C), was the consensus sequence for the highest intensity UV-induced 6-4PP adduct sites; while it was 5'-YTT*C for the highest intensity UV-induced CPD damage sites. These consensus tetranucleotides are composed entirely of consecutive pyrimidines and must have a DNA conformation that is highly productive for the absorption of UV photons. Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.

Micromechanical Modeling of Anisotropic Damage-Induced Permeability Variation in Crystalline Rocks

NASA Astrophysics Data System (ADS)

Chen, Yifeng; Hu, Shaohua; Zhou, Chuangbing; Jing, Lanru

2014-09-01

This paper presents a study on the initiation and progress of anisotropic damage and its impact on the permeability variation of crystalline rocks of low porosity. This work was based on an existing micromechanical model considering the frictional sliding and dilatancy behaviors of microcracks and the recovery of degraded stiffness when the microcracks are closed. By virtue of an analytical ellipsoidal inclusion solution, lower bound estimates were formulated through a rigorous homogenization procedure for the damage-induced effective permeability of the microcracks-matrix system, and their predictive limitations were discussed with superconducting penny-shaped microcracks, in which the greatest lower bounds were obtained for each homogenization scheme. On this basis, an empirical upper bound estimation model was suggested to account for the influences of anisotropic damage growth, connectivity, frictional sliding, dilatancy, and normal stiffness recovery of closed microcracks, as well as tensile stress-induced microcrack opening on the permeability variation, with a small number of material parameters. The developed model was calibrated and validated by a series of existing laboratory triaxial compression tests with permeability measurements on crystalline rocks, and applied for characterizing the excavation-induced damage zone and permeability variation in the surrounding granitic rock of the TSX tunnel at the Atomic Energy of Canada Limited's (AECL) Underground Research Laboratory (URL) in Canada, with an acceptable agreement between the predicted and measured data.

Statin-induced muscle damage and atrogin-1 induction is the result of a geranylgeranylation defect

PubMed Central

Cao, Peirang; Hanai, Jun-ichi; Tanksale, Preeti; Imamura, Shintaro; Sukhatme, Vikas P.; Lecker, Stewart H.

2009-01-01

Statins are widely used to treat hypercholesterolemia but can lead to a number of side effects in muscle, including rhabdomyolysis. Our recent findings implicated the induction of atrogin-1, a gene required for the development of muscle atrophy, in statin-induced muscle damage. Since statins inhibit many biochemical reactions besides cholesterol synthesis, we sought to define the statin-inhibited pathways responsible for atrogin-1 expression and muscle damage. We report here that lovastatin-induced atrogin-1 expression and muscle damage in cultured mouse myotubes and zebrafish can be prevented in the presence of geranylgeranol but not farnesol. Further, inhibitors of the transfer of geranylgeranyl isoprene units to protein targets cause statin muscle damage and atrogin-1 induction in cultured cells and in fish. These findings support the concept that dysfunction of small GTP-binding proteins lead to statin-induced muscle damage since these molecules require modification by geranylgeranyl moieties for their cellular localization and activity. Collectively, our animal and in vitro findings shed light on the molecular mechanism of statin-induced myopathy and suggest that atrogin-1 may be regulated by novel signaling pathways.—Cao, P., Hanai, J., Tanksale, P., Imamura, S., Sukhatme, V. P., Lecker, S. H. Statin-induced muscle damage and atrogin-1 induction is the result of a geranylgeranylation defect. PMID:19406843

Effects of fatigue induced damage on the longitudinal fracture resistance of cortical bone.

PubMed

Fletcher, Lloyd; Codrington, John; Parkinson, Ian

2014-07-01

As a composite material, cortical bone accumulates fatigue microdamage through the repetitive loading of everyday activity (e.g. walking). The accumulation of fatigue microdamage is thought to contribute to the occurrence of fragility fractures in older people. Therefore it is beneficial to understand the relationship between microcrack accumulation and the fracture resistance of cortical bone. Twenty longitudinally orientated compact tension fracture specimens were machined from a single bovine femur, ten specimens were assigned to both the control and fatigue damaged groups. The damaged group underwent a fatigue loading protocol to induce microdamage which was assessed via fluorescent microscopy. Following fatigue loading, non-linear fracture resistance tests were undertaken on both the control and damaged groups using the J-integral method. The interaction of the crack path with the fatigue induced damage and inherent toughening mechanisms were then observed using fluorescent microscopy. The results of this study show that fatigue induced damage reduces the initiation toughness of cortical bone and the growth toughness within the damage zone by three distinct mechanisms of fatigue-fracture interaction. Further analysis of the J-integral fracture resistance showed both the elastic and plastic component were reduced in the damaged group. For the elastic component this was attributed to a decreased number of ligament bridges in the crack wake while for the plastic component this was attributed to the presence of pre-existing fatigue microcracks preventing energy absorption by the formation of new microcracks.

Radon inhalation protects mice from carbon-tetrachloride-induced hepatic and renal damage.

PubMed

Kataoka, Takahiro; Nishiyama, Yuichi; Toyota, Teruaki; Yoshimoto, Masaaki; Sakoda, Akihiro; Ishimori, Yuu; Aoyama, Yutaka; Taguchi, Takehito; Yamaoka, Kiyonori

2011-12-01

We assessed whether radon inhalation provided protection from carbon tetrachloride (CCl4)-induced hepatic and renal damage in mice. Mice were subjected to intraperitoneal injection of CCl4 after inhaling approximately 18 kBq/m3 radon for 6 h. Radon inhalation significantly increased total glutathione (t-GSH) content and glutathione peroxidase (GPx) activity in the liver and kidney. Injection of CCl4 was associated with significantly higher levels of glutamic oxaloacetic transaminase (GOT) and alkaline phosphatase (ALP) activity and creatinine level in serum, and pretreatment with radon significantly decreased the GOT and ALP activity and creatinine level associated with CCl4 injection, suggesting that radon inhalation alleviates CCl4-induced hepatic and renal damage. The t-GSH contents and GPx activity in the liver and kidney of animals pretreated with radon were significantly higher than those of the CCl(4)-only group. These findings suggested that radon inhalation activated antioxidative functions and inhibited CCl4-induced hepatic and renal damage in mice.

Sleep loss and acute drug abuse can induce DNA damage in multiple organs of mice.

PubMed

Alvarenga, T A; Ribeiro, D A; Araujo, P; Hirotsu, C; Mazaro-Costa, R; Costa, J L; Battisti, M C; Tufik, S; Andersen, M L

2011-09-01

The purpose of the present study was to characterize the genetic damage induced by paradoxical sleep deprivation (PSD) in combination with cocaine or ecstasy (3,4-methylenedioxymethamphetamine; MDMA) in multiple organs of male mice using the single cell gel (comet) assay. C57BL/6J mice were submitted to PSD by the platform technique for 72 hours, followed by drug administration and evaluation of DNA damage in peripheral blood, liver and brain tissues. Cocaine was able to induce genetic damage in the blood, brain and liver cells of sleep-deprived mice at the majority of the doses evaluated. Ecstasy also induced increased DNA migration in peripheral blood cells for all concentrations tested. Analysis of damaged cells by the tail moment data suggests that ecstasy is a genotoxic chemical at the highest concentrations tested, inducing damage in liver or brain cells after sleep deprivation in mice. Taken together, our results suggest that cocaine and ecstasy/MDMA act as potent genotoxins in multiple organs of mice when associated with sleep loss.

Ion-irradiation-induced damage of steels characterized by means of nanoindentation

NASA Astrophysics Data System (ADS)

Heintze, C.; Recknagel, C.; Bergner, F.; Hernández-Mayoral, M.; Kolitsch, A.

2009-05-01

Self-ion irradiation was used to simulate the damage caused by fast neutrons in the austenitic stainless steel SS 304 SA, the ferritic/martensitic steel Eurofer'97 and a Fe-9 at.%Cr model alloy. The irradiation-induced hardness change in the damage layer was evaluated by means of nanoindentation. Three-step irradiations were performed at room temperature and 300 °C up to 1 and 10 dpa. An irradiation-induced hardness change was shown for all materials. No influence of irradiation temperature could be resolved. Irradiation-induced hardening exhibits different fluence dependencies in Eurofer'97 and Fe-9 at.%Cr. While the data indicate a saturation-like behaviour for Fe-9 at.%Cr, an increase of hardness with fluence up to 10 dpa was found for Eurofer'97.

Scaling Relations for Intercalation Induced Damage in Electrodes

DOE PAGES

Chen, Chien-Fan; Barai, Pallab; Smith, Kandler; ...

2016-04-02

Mechanical degradation, owing to intercalation induced stress and microcrack formation, is a key contributor to the electrode performance decay in lithium-ion batteries (LIBs). The stress generation and formation of microcracks are caused by the solid state diffusion of lithium in the active particles. Here in this work, scaling relations are constructed for diffusion induced damage in intercalation electrodes based on an extensive set of numerical experiments with a particle-level description of microcrack formation under disparate operating and cycling conditions, such as temperature, particle size, C-rate, and drive cycle. The microcrack formation and evolution in active particles is simulated based onmore » a stochastic methodology. A reduced order scaling law is constructed based on an extensive set of data from the numerical experiments. The scaling relations include combinatorial constructs of concentration gradient, cumulative strain energy, and microcrack formation. Lastly, the reduced order relations are further employed to study the influence of mechanical degradation on cell performance and validated against the high order model for the case of damage evolution during variable current vehicle drive cycle profiles.« less

Repair of DNA Damage Induced by the Cytidine Analog Zebularine Requires ATR and ATM in Arabidopsis[OPEN

PubMed Central

Liu, Chun-Hsin; Finke, Andreas; Díaz, Mariana; Rozhon, Wilfried; Poppenberger, Brigitte; Baubec, Tuncay; Pecinka, Ales

2015-01-01

DNA damage repair is an essential cellular mechanism that maintains genome stability. Here, we show that the nonmethylable cytidine analog zebularine induces a DNA damage response in Arabidopsis thaliana, independent of changes in DNA methylation. In contrast to genotoxic agents that induce damage in a cell cycle stage-independent manner, zebularine induces damage specifically during strand synthesis in DNA replication. The signaling of this damage is mediated by additive activity of ATAXIA TELANGIECTASIA MUTATED AND RAD3-RELATED and ATAXIA TELANGIECTASIA MUTATED kinases, which cause postreplicative cell cycle arrest and increased endoreplication. The repair requires a functional STRUCTURAL MAINTENANCE OF CHROMOSOMES5 (SMC5)-SMC6 complex and is accomplished predominantly by synthesis-dependent strand-annealing homologous recombination. Here, we provide insight into the response mechanism for coping with the genotoxic effects of zebularine and identify several components of the zebularine-induced DNA damage repair pathway. PMID:26023162

Dose-rate plays a significant role in synchrotron radiation X-ray-induced damage of rodent testes.

PubMed

Chen, Heyu; Wang, Ban; Wang, Caixia; Cao, Wei; Zhang, Jie; Ma, Yingxin; Hong, Yunyi; Fu, Shen; Wu, Fan; Ying, Weihai

2016-01-01

Synchrotron radiation (SR) X-ray has significant potential for applications in medical imaging and cancer treatment. However, the mechanisms underlying SR X-ray-induced tissue damage remain unclear. Previous studies on regular X-ray-induced tissue damage have suggested that dose-rate could affect radiation damage. Because SR X-ray has exceedingly high dose-rate compared to regular X-ray, it remains to be determined if dose-rate may affect SR X-ray-induced tissue damage. We used rodent testes as a model to investigate the role of dose-rate in SR X-ray-induced tissue damage. One day after SR X-ray irradiation, we determined the effects of the irradiation of the same dosage at two different dose-rates, 0.11 Gy/s and 1.1 Gy/s, on TUNEL signals, caspase-3 activation and DNA double-strand breaks (DSBs) of the testes. Compared to those produced by the irradiation at 0.11 Gy/s, irradiation at 1.1 Gy/s produced higher levels of DSBs, TUNEL signals, and caspase-3 activation in the testes. Our study has provided the first evidence suggesting that dose-rate could be a significant factor in SR X-ray-induced tissue damage, which may establish a valuable base for utilizing this factor to manipulate the tissue damage in SR X-ray-based medical applications.

Dose-rate plays a significant role in synchrotron radiation X-ray-induced damage of rodent testes

PubMed Central

Chen, Heyu; Wang, Ban; Wang, Caixia; Cao, Wei; Zhang, Jie; Ma, Yingxin; Hong, Yunyi; Fu, Shen; Wu, Fan; Ying, Weihai

2016-01-01

Synchrotron radiation (SR) X-ray has significant potential for applications in medical imaging and cancer treatment. However, the mechanisms underlying SR X-ray-induced tissue damage remain unclear. Previous studies on regular X-ray-induced tissue damage have suggested that dose-rate could affect radiation damage. Because SR X-ray has exceedingly high dose-rate compared to regular X-ray, it remains to be determined if dose-rate may affect SR X-ray-induced tissue damage. We used rodent testes as a model to investigate the role of dose-rate in SR X-ray-induced tissue damage. One day after SR X-ray irradiation, we determined the effects of the irradiation of the same dosage at two different dose-rates, 0.11 Gy/s and 1.1 Gy/s, on TUNEL signals, caspase-3 activation and DNA double-strand breaks (DSBs) of the testes. Compared to those produced by the irradiation at 0.11 Gy/s, irradiation at 1.1 Gy/s produced higher levels of DSBs, TUNEL signals, and caspase-3 activation in the testes. Our study has provided the first evidence suggesting that dose-rate could be a significant factor in SR X-ray-induced tissue damage, which may establish a valuable base for utilizing this factor to manipulate the tissue damage in SR X-ray-based medical applications. PMID:28078052

Comparison of Model Calculations of Biological Damage from Exposure to Heavy Ions with Measurements

NASA Astrophysics Data System (ADS)

Kim, Myung-Hee Y.; Wu, Honglu; Hada, Megumi; Cucinotta, Francis

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 g or X rays, the presence of shielding does not always reduce the radiation risks for energetic charged-particle exposure. Dose delivered by the charged particle increases sharply at 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. Measurements of the induction of micronuclei (MN) have made 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. Although the data did not reveal an increased yield of MN at the location of the Bragg peak, the increased inhibition of cell progression, which is related to cell death, was found at the Bragg peak location. These results are compared to the calculations of biological damage using a stochastic Monte-Carlo track structure model, Galactic Cosmic Ray Event-based Risk Model (GERM) code (Cucinotta et al., 2011). The GERM code estimates the basic physical properties along the passage of heavy ions in tissue and shielding materials, by which the experimental set-up can be interpreted. The code can also be used to describe the biophysical events of interest in radiobiology, cancer therapy, and space exploration. The calculation has shown that the severely damaged cells at the Bragg peak are more likely to go through reproductive death, the so called “overkill”. F. A. Cucinotta, I. Plante, A. L. Ponomarev, and M. Y. Kim, Nuclear Interactions in Heavy Ion Transport and Event

Catastrophic nanosecond laser induced damage in the bulk of potassium titanyl phosphate crystals

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wagner, Frank R., E-mail: frank.wagner@fresnel.fr; Natoli, Jean-Yves; Akhouayri, Hassan

2014-06-28

Due to its high effective nonlinearity and the possibility to produce periodically poled crystals, potassium titanyl phosphate (KTiOPO{sub 4}, KTP) is still one of the economically important nonlinear optical materials. In this overview article, we present a large study on catastrophic nanosecond laser induced damage in this material and the very similar RbTiOPO{sub 4} (RTP). Several different systematic studies are included: multiple pulse laser damage, multi-wavelength laser damage in KTP, damage resistance anisotropy, and variations of the laser damage thresholds for RTP crystals of different qualities. All measurements were carried out in comparable experimental conditions using a 1064 nm Q-switched lasermore » and some were repeated at 532 nm. After summarizing the experimental results, we detail the proposed model for laser damage in this material and discuss the experimental results in this context. According to the model, nanosecond laser damage is caused by light-induced generation of transient laser-damage precursors which subsequently provide free electrons that are heated by the same nanosecond pulse. We also present a stimulated Raman scattering measurement and confront slightly different models to the experimental data. Finally, the physical nature of the transient damage precursors is discussed and similarities and differences to laser damage in other crystals are pointed out.« less

Apitherapy products enhance the recovery of CCL4-induced hepatic damages in rats.

PubMed

Saral, Özlem; Yildiz, Oktay; Aliyazicioğlu, Rezzan; Yuluğ, Esin; Canpolat, Sinan; Öztürk, Ferhat; Kolayli, Sevgi

2016-01-05

Our objective was to identify the antioxidant properties of honeybee products from Turkey, chestnut honey, pollen, propolis, and royal jelly, and their hepatoprotective activity against CCl4-induced hepatic damage in rats. Animals were fed with honeybee products for 7 days following CCl4 injection. Development of liver damage and oxidative stress were monitored by measuring the activities of the enzymes alanine transaminase, aspartate transaminase, malondialdehyde, superoxide dismutase, and catalase. Antioxidant capacities of the bee products were identified using FRAP and DPPH assays, as well as by measuring total phenolic and flavonoid contents. The antioxidant activities of the honeybee products were highest in propolis, followed, in order, by pollen, honey, and royal jelly. Despite their different levels of antioxidant capacity, their roles in the prevention of liver damage induced by CCl4 were very similar, which can be explained through their bioavailability to the treated animals. Our results suggest that honey, propolis, pollen, and royal jelly significantly enhanced the healing of CCl4-induced liver damage, partially due to their antioxidant properties and bioavailability.

Hypoxic pretreatment protects against neuronal damage of the rat hippocampus induced by severe hypoxia.

PubMed

Gorgias, N; Maidatsi, P; Tsolaki, M; Alvanou, A; Kiriazis, G; Kaidoglou, K; Giala, M

1996-04-01

The present study investigates whether under conditions of successive hypoxic exposures pretreatment with mild (15% O(2)) or moderate (10% O(2)) hypoxia, protects hippocampal neurones against damage induced by severe (3% O(2)) hypoxia. The ultrastructural findings were also correlated with regional superoxide dismutase (SOD) activity changes. In unpretreated rats severe hypoxia induced ultrastructural changes consistent with the aspects of delayed neuronal death (DND). However, in preexposed animals hippocampal damage was attenuated in an inversely proportional way with the severity of the hypoxic pretreatment. The ultrastructural hypoxic tolerance findings were also closely related to increased regional SOD activity levels. Thus the activation of the endogenous antioxidant defense by hypoxic preconditioning, protects against hippocampal damage induced by severe hypoxia. The eventual contribution of increased endogenous adenosine and/or reduced excitotoxicity to induce hypoxic tolerance is discussed.

Antagonist effects of veratric acid against UVB-induced cell damages.

PubMed

Shin, Seoung Woo; Jung, Eunsun; Kim, Seungbeom; Lee, Kyung-Eun; Youm, Jong-Kyung; Park, Deokhoon

2013-05-10

Ultraviolet (UV) radiation induces DNA damage, oxidative stress, and inflammatory processes in human epidermis, resulting in inflammation, photoaging, and photocarcinogenesis. Adequate protection of skin against the harmful effect of UV irradiation is essential. In recent years naturally occurring herbal compounds such as phenolic acids, flavonoids, and high molecular weight polyphenols have gained considerable attention as beneficial protective agents. The simple phenolic veratric acid (VA, 3,4-dimethoxybenzoic acid) is one of the major benzoic acid derivatives from vegetables and fruits and it also occurs naturally in medicinal mushrooms which have been reported to have anti-inflammatory and anti-oxidant activities. However, it has rarely been applied in skin care. This study, therefore, aimed to explore the possible roles of veratric acid in protection against UVB-induced damage in HaCaT cells. Results showed that veratric acid can attenuate cyclobutane pyrimidine dimers (CPDs) formation, glutathione (GSH) depletion and apoptosis induced by UVB. Furthermore, veratric acid had inhibitory effects on the UVB-induced release of the inflammatory mediators such as IL-6 and prostaglandin-E2. We also confirmed the safety and clinical efficacy of veratric acid on human skin. Overall, results demonstrated significant benefits of veratric acid on the protection of keratinocyte against UVB-induced injuries and suggested its potential use in skin photoprotection.

Neutral beam and ICP etching of HKMG MOS capacitors: Observations and a plasma-induced damage model

NASA Astrophysics Data System (ADS)

Kuo, Tai-Chen; Shih, Tzu-Lang; Su, Yin-Hsien; Lee, Wen-Hsi; Current, Michael Ira; Samukawa, Seiji

2018-04-01

In this study, TiN/HfO2/Si metal-oxide-semiconductor (MOS) capacitors were etched by a neutral beam etching technique under two contrasting conditions. The configurations of neutral beam etching technique were specially designed to demonstrate a "damage-free" condition or to approximate "reactive-ion-etching-like" conditions to verify the effect of plasma-induced damage on electrical characteristics of MOS capacitors. The results show that by neutral beam etching (NBE), the interface state density (Dit) and the oxide trapped charge (Qot) were lower than routine plasma etching. Furthermore, the decrease in capacitor size does not lead to an increase in leakage current density, indicating less plasma induced side-wall damage. We present a plasma-induced gate stack damage model which we demonstrate by using these two different etching configurations. These results show that NBE is effective in preventing plasma-induced damage at the high-k/Si interface and on the high-k oxide sidewall and thus improve the electrical performance of the gate structure.

Prevention of UVB Radiation-induced Epidermal Damage by Expression of Heat Shock Protein 70*

PubMed Central

Matsuda, Minoru; Hoshino, Tatsuya; Yamashita, Yasuhiro; Tanaka, Ken-ichiro; Maji, Daisuke; Sato, Keizo; Adachi, Hiroaki; Sobue, Gen; Ihn, Hironobu; Funasaka, Yoko; Mizushima, Tohru

2010-01-01

Irradiation with UV light, especially UVB, causes epidermal damage via the induction of apoptosis, inflammatory responses, and DNA damage. Various stressors, including UV light, induce heat shock proteins (HSPs) and the induction, particularly that of HSP70, provides cellular resistance to such stressors. The anti-inflammatory activity of HSP70, such as its inhibition of nuclear factor kappa B (NF-κB), was recently revealed. These in vitro results suggest that HSP70 protects against UVB-induced epidermal damage. Here we tested this idea by using transgenic mice expressing HSP70 and cultured keratinocytes. Irradiation of wild-type mice with UVB caused epidermal damage such as induction of apoptosis, which was suppressed in transgenic mice expressing HSP70. UVB-induced apoptosis in cultured keratinocytes was suppressed by overexpression of HSP70. Irradiation of wild-type mice with UVB decreased the cutaneous level of IκB-α (an inhibitor of NF-κB) and increased the infiltration of leukocytes and levels of pro-inflammatory cytokines and chemokines in the epidermis. These inflammatory responses were suppressed in transgenic mice expressing HSP70. In vitro, the overexpression of HSP70 suppressed the expression of pro-inflammatory cytokines and chemokines and increased the level of IκB-α in keratinocytes irradiated with UVB. UVB induced an increase in cutaneous levels of cyclobutane pyrimidine dimers and 8-hydroxy-2′-deoxyguanosine, both of which were suppressed in transgenic mice expressing HSP70. This study provides genetic evidence that HSP70 protects the epidermis from UVB-induced radiation damage. The findings here also suggest that the protective action of HSP70 is mediated by anti-apoptotic, anti-inflammatory, and anti-DNA damage effects. PMID:20018843

Genoprotective effect of hyaluronic acid against benzalkonium chloride-induced DNA damage in human corneal epithelial cells

PubMed Central

Wu, Han; Zhang, Huina; Wang, Changjun; Wu, Yihua; Xie, Jiajun; Jin, Xiuming; Yang, Jun

2011-01-01

Purpose The aim of this study was to investigate hyaluronic acid (HA) protection on cultured human corneal epithelial cells (HCEs) against benzalkonium chloride (BAC)-induced DNA damage and intracellular reactive oxygen species (ROS) increase. Methods Cells were incubated with different concentrations of BAC with or without the presence of 0.2% HA for 30 min. DNA damage to HCEs was examined by alkaline comet assay and by immunofluorescence microscopic detection of the phosphorylated form of histone variant H2AX (γH2AX) foci. ROS production was assessed by the fluorescent probe, 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA). Cell apoptosis was determined with annexin V staining by flow cytometry. Results HA significantly reduced BAC-induced DNA damage as indicated by the tail length (TL) and tail moment (TM) of alkaline comet assay and by γH2AX foci formation, respectively. Moreover, HA significantly decreased BAC-induced ROS increase and cell apoptosis. However, exposure to HA alone did not produce any significant change in DNA damage, ROS generation, or cell apoptosis. Conclusions BAC could induce DNA damage and cell apoptosis in HCEs, probably through increasing oxidative stress. Furthermore, HA was an effective protective agent that had antioxidant properties and could decrease DNA damage and cell apoptosis induced by BAC. PMID:22219631

Intestinal bacteria are necessary for doxorubicin-induced intestinal damage but not for doxorubicin-induced apoptosis.

PubMed

Rigby, Rachael J; Carr, Jacquelyn; Orgel, Kelly; King, Stephanie L; Lund, P Kay; Dekaney, Christopher M

2016-09-02

Doxorubicin (DOXO) induces significant, but transient, increases in apoptosis in the stem cell zone of the jejunum, followed by mucosal damage involving a decrease in crypt proliferation, crypt number, and villus height. The gastrointestinal tract is home to a vast population of commensal bacteria and numerous studies have demonstrated a symbiotic relationship between intestinal bacteria and intestinal epithelial cells (IEC) in maintaining homeostatic functions of the intestine. However, whether enteric bacteria play a role in DOXO-induced damage is not well understood. We hypothesized that enteric bacteria are necessary for induction of apoptosis and damage associated with DOXO treatment. Conventionally raised (CONV) and germ free (GF) mice were given a single injection of DOXO, and intestinal tissue was collected at 6, 72, and 120 h after treatment and from no treatment (0 h) controls. Histology and morphometric analyses quantified apoptosis, mitosis, crypt depth, villus height, and crypt density. Immunostaining for muc2 and lysozyme evaluated Paneth cells, goblet cells or dual stained intermediate cells. DOXO administration induced significant increases in apoptosis in jejunal epithelium regardless of the presence of enteric bacteria; however, the resulting injury, as demonstrated by statistically significant changes in crypt depth, crypt number, and proliferative cell number, was dependent upon the presence of enteric bacteria. Furthermore, we observed expansion of Paneth and goblet cells and presence of intermediate cells only in CONV and not GF mice. These findings provide evidence that manipulation and/or depletion of the enteric microbiota may have clinical significance in limiting chemotherapy-induced mucositis.

Genomic damage induced by 1-MHz ultrasound in vitro.

PubMed

Udroiu, Ion; Marinaccio, Jessica; Bedini, Angelico; Giliberti, Claudia; Palomba, Raffaele; Sgura, Antonella

2018-01-01

Genotoxic effects of therapeutic ultrasound are poorly documented, when compared with the wide use of this physical agent. The aim of this work was to investigate the clastogenic and aneugenic potential of 1 MHz ultrasound, employing intensities (200 and 300 mW/cm 2 ) above the cavitational threshold, but in the range of those normally used in therapeutics. Both normal fibroblasts (AG01522) and tumoral cells (MCF-7) were sonicated. While no effects on viability were noted, significant increases of CREST-negative micronuclei (indicative of clastogenesis) and CREST-positive micronuclei (indicative of aneuploidy) were detected. Clastogenesis was confirmed by increases of γ-H2AX foci, while increases of spindle anomalies confirmed the induction of aneuploidy. Our results confirm previous works that showed ultrasound-induced DNA breakage. Moreover, our experiments show that the known effect of ultrasound-induced damage to microtubules is also able to damage the mitotic spindle and induce aneuploidy. On the overall, this work highlights the importance to further investigate the potential risks related to therapeutics US. Environ. Mol. Mutagen. 59:60-68, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Gastric damage and granulocyte infiltration induced by indomethacin in tumour necrosis factor receptor 1 (TNF-R1) or inducible nitric oxide synthase (iNOS) deficient mice

PubMed Central

Souza, M H L P; Lemos, H. Paula; Oliveira, R B; Cunha, F Q

2004-01-01

Background: Tumour necrosis factor α (TNF-α) is involved in non-steroidal anti-inflammatory drug induced gastropathy. Nitric oxide (NO) is a mediator of gastrointestinal mucosal defence but, paradoxically, it also contributes to mucosal damage. Aims: We optimised the C57BL/6 mouse model of indomethacin induced gastropathy to evaluate the role of TNF-α and inducible nitric oxide synthase (iNOS) generated NO in gastric damage and granulocyte infiltration using tumour necrosis factor receptor 1 (TNF-R1−/−) or iNOS (iNOS−/−) deficient mice. Methods: Different doses of indomethacin (2.5, 5, 10, 20 mg/kg) were administered and animals were assessed 6, 12, or 24 hours later. Gastric damage was measured by the sum of all erosions in the gastric mucosa, and gastric granulocyte infiltration was determined by myeloperoxidase (MPO) activity. Other groups of wild-type mice received thalidomide, dexamethasone, fucoidin, l-NAME, or 1400W, and then indomethacin was administered. Additionally, indomethacin was administered to TNF-R1−/− or iNOS−/−. Gastric damage and MPO activity were evaluated 12 hours later. Results: Indomethacin induced dose and time dependent gastric damage and increase in MPO activity in wild-type mice, with the greatest effect at a dose of 10 mg/kg and after 12 hours. Treatment with thalidomide, dexamethasone, or fucoidin reduced gastric damage and MPO activity induced by indomethacin. After indomethacin administration, TNF-R1−/− had less gastric damage and MPO activity than controls. Genetic (knockout mice) or pharmacological (1400W and l-NAME) inhibition of iNOS activity reduced indomethacin induced gastric damage, despite no reduction in MPO activity. Conclusion: TNF-α, acting via TNF-R1, is involved in indomethacin induced gastric damage and granulocyte infiltration. Furthermore, iNOS generated NO is involved in gastric damage induced by indomethacin. PMID:15138204

Depletion of enteric bacteria diminishes leukocyte infiltration following doxorubicin-induced small intestinal damage in mice.

PubMed

Carr, Jacquelyn S; King, Stephanie; Dekaney, Christopher M

2017-01-01

While enteric bacteria have been shown to play a critical role in other forms of intestinal damage, their role in mediating the response to the chemotherapeutic drug Doxorubicin (Doxo) is unclear. In this study, we used a mouse model of intestinal bacterial depletion to evaluate the role enteric bacteria play in mediating Doxo-induced small intestinal damage and, more specifically, in mediating chemokine expression and leukocyte infiltration following Doxo treatment. An understanding of this pathway may allow for development of intervention strategies to reduce chemotherapy-induced small intestinal damage. Mice were treated with (Abx) or without (NoAbx) oral antibiotics in drinking water for four weeks and then with Doxo. Jejunal tissues were collected at various time points following Doxo treatment and stained and analyzed for apoptosis, crypt damage and restitution, and macrophage and neutrophil number. In addition, RNA expression of inflammatory markers (TNFα, IL1-β, IL-10) and cytokines (CCL2, CC7, KC) was assessed by qRT-PCR. In NoAbx mice Doxo-induced damage was associated with rapid induction of apoptosis in jejunal crypt epithelium and an increase weight loss and crypt loss. In addition, we observed an increase in immune-modulating chemokines CCL2, CCL7 and KC and infiltration of macrophages and neutrophils. In contrast, while still positive for induction of apoptosis following Doxo treatment, Abx mice showed neither the overall weight loss nor crypt loss seen in NoAbx mice nor the increased chemokine expression and leukocyte infiltration. Enteric bacteria play a critical role in Doxo-induced small intestinal damage and are associated with an increase in immune-modulating chemokines and cells. Manipulation of enteric bacteria or the damage pathway may allow for prevention or treatment of chemotherapy-induced small intestinal damage.

FURTHER EVIDENCE THAT DICHLOROMETHANE DOES NOT INDUCE CHROMOSOME DAMAGE

EPA Science Inventory

Dichloromethane (DCM) is a widely used industrial solvent which has been determined to be a carcinogen in rats and mice. n vitro and in vivo analyses of chromosome damage induced by this agent have provided conflicting results. n order to further investigate the clastogenic poten...

Optical and electrical characterization methods of plasma-induced damage in silicon nitride films

NASA Astrophysics Data System (ADS)

Kuyama, Tomohiro; Eriguchi, Koji

2018-06-01

We proposed evaluation methods of plasma-induced damage (PID) in silicon nitride (SiN) films. The formation of an oxide layer by air exposure was identified for damaged SiN films by X-ray photoelectron spectroscopy (XPS). Bruggeman’s effective medium approximation was employed for an optical model consisting of damaged and undamaged layers, which is applicable to an in-line monitoring by spectroscopic ellipsometry (SE). The optical thickness of the damaged layer — an oxidized layer — extended after plasma exposure, which was consistent with the results obtained by a diluted hydrofluoric acid (DHF) wet etching. The change in the conduction band edge of the damaged SiN films was presumed from two electrical techniques, i.e., current–voltage (I–V) measurement and time-dependent dielectric breakdown (TDDB) test with a constant voltage stress. The proposed techniques can be used for assigning the plasma-induced structural change in an SiN film widely used as an etch-protecting layer.

Endotoxin-induced lung alveolar cell injury causes brain cell damage.

PubMed

Rodríguez-González, Raquel; Ramos-Nuez, Ángela; Martín-Barrasa, José Luis; López-Aguilar, Josefina; Baluja, Aurora; Álvarez, Julián; Rocco, Patricia R M; Pelosi, Paolo; Villar, Jesús

2015-01-01

Sepsis is the most common cause of acute respiratory distress syndrome, a severe lung inflammatory disorder with an elevated morbidity and mortality. Sepsis and acute respiratory distress syndrome involve the release of inflammatory mediators to the systemic circulation, propagating the cellular and molecular response and affecting distal organs, including the brain. Since it has been reported that sepsis and acute respiratory distress syndrome contribute to brain dysfunction, we investigated the brain-lung crosstalk using a combined experimental in vitro airway epithelial and brain cell injury model. Conditioned medium collected from an in vitro lipopolysaccharide-induced airway epithelial cell injury model using human A549 alveolar cells was subsequently added at increasing concentrations (no conditioned, 2%, 5%, 10%, 15%, 25%, and 50%) to a rat mixed brain cell culture containing both astrocytes and neurons. Samples from culture media and cells from mixed brain cultures were collected before treatment, and at 6 and 24 h for analysis. Conditioned medium at 15% significantly increased apoptosis in brain cell cultures 24 h after treatment, whereas 25% and 50% significantly increased both necrosis and apoptosis. Levels of brain damage markers S100 calcium binding protein B and neuron-specific enolase, interleukin-6, macrophage inflammatory protein-2, as well as matrix metalloproteinase-9 increased significantly after treating brain cells with ≥2% conditioned medium. Our findings demonstrated that human epithelial pulmonary cells stimulated with bacterial lipopolysaccharide release inflammatory mediators that are able to induce a translational clinically relevant and harmful response in brain cells. These results support a brain-lung crosstalk during sepsis and sepsis-induced acute respiratory distress syndrome. © 2014 by the Society for Experimental Biology and Medicine.

Bactericidal antibiotics induce mitochondrial dysfunction and oxidative damage in Mammalian cells.

PubMed

Kalghatgi, Sameer; Spina, Catherine S; Costello, James C; Liesa, Marc; Morones-Ramirez, J Ruben; Slomovic, Shimyn; Molina, Anthony; Shirihai, Orian S; Collins, James J

2013-07-03

Prolonged antibiotic treatment can lead to detrimental side effects in patients, including ototoxicity, nephrotoxicity, and tendinopathy, yet the mechanisms underlying the effects of antibiotics in mammalian systems remain unclear. It has been suggested that bactericidal antibiotics induce the formation of toxic reactive oxygen species (ROS) in bacteria. We show that clinically relevant doses of bactericidal antibiotics-quinolones, aminoglycosides, and β-lactams-cause mitochondrial dysfunction and ROS overproduction in mammalian cells. We demonstrate that these bactericidal antibiotic-induced effects lead to oxidative damage to DNA, proteins, and membrane lipids. Mice treated with bactericidal antibiotics exhibited elevated oxidative stress markers in the blood, oxidative tissue damage, and up-regulated expression of key genes involved in antioxidant defense mechanisms, which points to the potential physiological relevance of these antibiotic effects. The deleterious effects of bactericidal antibiotics were alleviated in cell culture and in mice by the administration of the antioxidant N-acetyl-l-cysteine or prevented by preferential use of bacteriostatic antibiotics. This work highlights the role of antibiotics in the production of oxidative tissue damage in mammalian cells and presents strategies to mitigate or prevent the resulting damage, with the goal of improving the safety of antibiotic treatment in people.

Methylphenidate and Amphetamine Do Not Induce Cytogenetic Damage in Lymphocytes of Children with ADHD

ERIC Educational Resources Information Center

Witt, Kristine L.; Shelby, Michael D.; Itchon-Ramos, Nilda; Faircloth, Melissa; Kissling, Grace E.; Chrisman, Allan K.; Ravi, Hima; Murli, Hemalatha; Mattison, Donald R.; Kollins, Scott H.

2008-01-01

The inducement of chromosomal damage in lymphocytes among children with attention deficit hyperactivity disorder receiving treatment with methylphenidate- or amphetamine-based drugs is investigated. Findings did not reveal significant increases in cytogenetic damage related to the treatment. The risk for cytogenetic damage posed by such products…

The thyroid hormone receptor β induces DNA damage and premature senescence.

PubMed

Zambrano, Alberto; García-Carpizo, Verónica; Gallardo, María Esther; Villamuera, Raquel; Gómez-Ferrería, Maria Ana; Pascual, Angel; Buisine, Nicolas; Sachs, Laurent M; Garesse, Rafael; Aranda, Ana

2014-01-06

There is increasing evidence that the thyroid hormone (TH) receptors (THRs) can play a role in aging, cancer and degenerative diseases. In this paper, we demonstrate that binding of TH T3 (triiodothyronine) to THRB induces senescence and deoxyribonucleic acid (DNA) damage in cultured cells and in tissues of young hyperthyroid mice. T3 induces a rapid activation of ATM (ataxia telangiectasia mutated)/PRKAA (adenosine monophosphate-activated protein kinase) signal transduction and recruitment of the NRF1 (nuclear respiratory factor 1) and THRB to the promoters of genes with a key role on mitochondrial respiration. Increased respiration leads to production of mitochondrial reactive oxygen species, which in turn causes oxidative stress and DNA double-strand breaks and triggers a DNA damage response that ultimately leads to premature senescence of susceptible cells. Our findings provide a mechanism for integrating metabolic effects of THs with the tumor suppressor activity of THRB, the effect of thyroidal status on longevity, and the occurrence of tissue damage in hyperthyroidism.

Coagulin-L ameliorates TLR4 induced oxidative damage and immune response by regulating mitochondria and NOX-derived ROS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reddy, Sukka Santosh

Withanolides possess diverse biological and pharmacological activity but their immunomodulatory function is less realized. Hence, coagulin-L, a withanolide isolated from Withania coagulans Dunal has been studied for such an effect in human and murine cells, and mice model. Coagulin-L (1, 3, 10 μM) exhibited immunomodulatory effect by suppressing TLR4 induced immune mediators such as cytokines (GMCSF, IFNα, IFNγ, IL-1α, IL-1Rα, IL-1β, IL-2, IL-2R, IL-4, IL-5, IL-6, IL-7, IL-10, IL-12 (p40/p70), IL-13, IL-15, IL-17), chemokines (IL-8/CXCL8, MIG/CXCL9, IP-10/CXCL10, KC, MCP-1/CCL2, MIP-1α/CCL3, MIP-1β/CCL4, RANTES/CCL5, eotaxin/CCL11), growth factors (FGF-basic, VEGF), nitric oxide and intracellular superoxide. Mechanistically, coagulin-L abrogated LPS induced total and mitochondrialmore » ROS generation, NOX2, NOX4 mRNA expression, IRAK and MAPK (p38, JNK, ERK) activation. Coagulin-L also attenuated IκBα degradation, which prevented NFκB downstream iNOS expression and pro-inflammatory cytokine release. Furthermore, coagulin-L (10, 25, 50 mg/kg, p.o.), undermined the LPS (10 mg/kg, i.p.) induced endotoxemia response in mice as evinced from diminished cytokine release, nitric oxide, aortic p38 MAPK activation and endothelial tissue impairment besides suppressing NOX2 and NOX4 expression in liver and aorta. Moreover, coagulin-L also alleviated the ROS mediated oxidative damage which was assessed through protein carbonyl, lipid hydroperoxide, 8-isoprostane and 8-hydroxy-2-deoxyguanosine quantification. To extend, coagulin-L also suppressed carrageenan-induced paw edema and thioglycollate-induced peritonitis in mice. Therefore, coagulin-L can be of therapeutic importance in pathological conditions induced by oxidative damage. - Highlights: • Coagulin-L demonstrates immunomodulatory effects in vivo and in vitro by modulating ROS. • Coagulin-L modulates TH1/TH2/TH17 immunokines. • Coagulin-L exerts immunomodulatory effect by regulating TLR4-IRAK- ROS

In vivo gamma-rays induced initial DNA damage and the effect of famotidine in mouse leukocytes as assayed by the alkaline comet assay.

PubMed

Mozdarani, Hossein; Nasirian, Borzo; Haeri, S Abolghasem

2007-03-01

Ionizing radiation induces a variety of lesions in DNA, each of which can be used as a bio-indicator for biological dosimetry or the study of the radioprotective effects of substances. To assess gamma ray-induced DNA damage in vivo in mouse leukocytes at various doses and the effect of famotidine, blood was collected from Balb/c male mice after irradiation with 4 Gy gamma-rays at different time intervals post-irradiation. To assess the response, mice were irradiated with doses of gamma-rays at 1 to 4 Grays. Famotidine was injected intra-peritoneally (i.p) at a dose of 5 mg/kg at various time intervals before irradiation. Four slides were prepared from each sample and alkaline comet assay was performed using standard protocols. Results obtained show that radiation significantly increases DNA damage in leukocytes in a dose dependent manner (p < 0.01) when using appropriate sampling time after irradiation, because increasing sampling time after irradiation resulted in a time dependent disappearance of DNA damage. Treatment with only 5 mg/kg famotidine before 4 Gy irradiation led to almost 50% reduction in DNA damage when compared with those animals which received radiation alone. The radioprotective capability of famotidine might be attributed to radical scavenging properties and an anti-oxidation mechanism.

Muscle damage and repeated bout effect induced by enhanced eccentric squats.

PubMed

Coratella, Giuseppe; Chemello, Alessandro; Schena, Federico

2016-12-01

Muscle damage and repeated bout effect have been studied after pure eccentric-only exercise. The aim of this study was to evaluate muscle damage and repeated bout effect induced by enhanced eccentric squat exercise using flywheel device. Thirteen healthy males volunteered for this study. Creatine kinase blood activity (CK), quadriceps isometric peak torque and muscle soreness were used as markers of muscle damage. The dependent parameters were measured at baseline, immediately after and each day up to 96 hours after the exercise session. The intervention consisted of 100 repetitions of enhanced eccentric squat exercise using flywheel device. The same protocol was repeated after 4 weeks. After the first bout, CK and muscle soreness were significantly greater (P<0.05) than baseline respectively up to 72 and 96 hours. Isometric peak torque was significantly lower (P<0.05) up to 72 hours. After the second bout, CK showed no significant increase (P>0.05), while isometric peak torque and muscle soreness returned to values similar to baseline after respectively 48 and 72 hours. All muscle damage markers were significantly lower after second compared to first bout. The enhanced eccentric exercise induced symptoms of muscle damage up to 96 hours. However, it provided muscle protection after the second bout, performed four weeks later. Although it was not eccentric-only exercise, the enhancement of eccentric phase provided muscle protection.

GUI to Facilitate Research on Biological Damage from Radiation

NASA Technical Reports Server (NTRS)

Cucinotta, Frances A.; Ponomarev, Artem Lvovich

2010-01-01

A graphical-user-interface (GUI) computer program has been developed to facilitate research on the damage caused by highly energetic particles and photons impinging on living organisms. The program brings together, into one computational workspace, computer codes that have been developed over the years, plus codes that will be developed during the foreseeable future, to address diverse aspects of radiation damage. These include codes that implement radiation-track models, codes for biophysical models of breakage of deoxyribonucleic acid (DNA) by radiation, pattern-recognition programs for extracting quantitative information from biological assays, and image-processing programs that aid visualization of DNA breaks. The radiation-track models are based on transport models of interactions of radiation with matter and solution of the Boltzmann transport equation by use of both theoretical and numerical models. The biophysical models of breakage of DNA by radiation include biopolymer coarse-grained and atomistic models of DNA, stochastic- process models of deposition of energy, and Markov-based probabilistic models of placement of double-strand breaks in DNA. The program is designed for use in the NT, 95, 98, 2000, ME, and XP variants of the Windows operating system.

House dust mite-induced asthma causes oxidative damage and DNA double-strand breaks in the lungs.

PubMed

Chan, Tze Khee; Loh, Xin Yi; Peh, Hong Yong; Tan, W N Felicia; Tan, W S Daniel; Li, Na; Tay, Ian J J; Wong, W S Fred; Engelward, Bevin P

2016-07-01

Asthma is related to airway inflammation and oxidative stress. High levels of reactive oxygen and nitrogen species can induce cytotoxic DNA damage. Nevertheless, little is known about the possible role of allergen-induced DNA damage and DNA repair as modulators of asthma-associated pathology. We sought to study DNA damage and DNA damage responses induced by house dust mite (HDM) in vivo and in vitro. We measured DNA double-strand breaks (DSBs), DNA repair proteins, and apoptosis in an HDM-induced allergic asthma model and in lung samples from asthmatic patients. To study DNA repair, we treated mice with the DSB repair inhibitor NU7441. To study the direct DNA-damaging effect of HDM on human bronchial epithelial cells, we exposed BEAS-2B cells to HDM and measured DNA damage and reactive oxygen species levels. HDM challenge increased lung levels of oxidative damage to proteins (3-nitrotyrosine), lipids (8-isoprostane), and nucleic acid (8-oxoguanine). Immunohistochemical evidence for HDM-induced DNA DSBs was revealed by increased levels of the DSB marker γ Histone 2AX (H2AX) foci in bronchial epithelium. BEAS-2B cells exposed to HDM showed enhanced DNA damage, as measured by using the comet assay and γH2AX staining. In lung tissue from human patients with asthma, we observed increased levels of DNA repair proteins and apoptosis, as shown by caspase-3 cleavage, caspase-activated DNase levels, and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling staining. Notably, NU7441 augmented DNA damage and cytokine production in the bronchial epithelium and apoptosis in the allergic airway, implicating DSBs as an underlying driver of asthma pathophysiology. This work calls attention to reactive oxygen and nitrogen species and HDM-induced cytotoxicity and to a potential role for DNA repair as a modulator of asthma-associated pathophysiology. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Contraction-induced muscle damage is unaffected by vitamin E supplementation.

PubMed

Beaton, Louise J; Allan, Damon A; Tarnopolsky, Mark A; Tiidus, Peter M; Phillips, Stuart M

2002-05-01

Vitamin E supplementation may confer a protective effect against eccentrically biased exercise-induced muscle damage through stabilization of the cell membrane and possibly via inhibition of free radical formation. Evidence supporting a protective role of vitamin E after contraction-induced muscle injury in humans is, however, inconsistent. The present study sought to determine the effect of vitamin E supplementation on indices of exercise-induced muscle damage and the postexercise inflammatory response after performance of repeated eccentric muscle contractions. Young healthy men performed a bout of 240 maximal isokinetic eccentric muscle contractions (0.52 rad.s-1) after being supplemented for 30 d with either vitamin E (N = 9; 1200 IU.d-1) or placebo (N = 7; safflower oil). Measurements of torque (isometric and concentric) decreased (P < 0.05) below preexercise values immediately post- and at 48 h post-exercise. Biopsies taken 24 h postexercise showed a significant increase in the amount of extensive Z-band disruption (P < 0.01); however, neither the torque deficit nor the extent of Z-band disruption were affected by vitamin E. Exercise resulted in increased macrophage cell infiltration (P = 0.05) into muscle, which was also unaffected by vitamin E. Serum CK also increased as a result of the exercise (P < 0.05) with no effect of vitamin E. We conclude that vitamin E supplementation (30 d at 1200 IU.d-1), which resulted in a 2.8-fold higher serum vitamin E concentration (P < 0.01), had no affect on indices of contraction-induced muscle damage nor inflammation (macrophage infiltration) as a result of eccentrically biased muscle contractions.

Plasma induced DNA damage: Comparison with the effects of ionizing radiation

NASA Astrophysics Data System (ADS)

Lazović, S.; Maletić, D.; Leskovac, A.; Filipović, J.; Puač, N.; Malović, G.; Joksić, G.; Petrović, Z. Lj.

2014-09-01

We use human primary fibroblasts for comparing plasma and gamma rays induced DNA damage. In both cases, DNA strand breaks occur, but of fundamentally different nature. Unlike gamma exposure, contact with plasma predominantly leads to single strand breaks and base-damages, while double strand breaks are mainly consequence of the cell repair mechanisms. Different cell signaling mechanisms are detected confirming this (ataxia telangiectasia mutated - ATM and ataxia telangiectasia and Rad3 related - ATR, respectively). The effective plasma doses can be tuned to match the typical therapeutic doses of 2 Gy. Tailoring the effective dose through plasma power and duration of the treatment enables safety precautions mainly by inducing apoptosis and consequently reduced frequency of micronuclei.

Mitochondria regulate DNA damage and genomic instability induced by high LET radiation

NASA Astrophysics Data System (ADS)

Zhang, Bo; Davidson, Mercy M.; Hei, Tom K.

2014-04-01

High linear energy transfer (LET) radiation including α particles and heavy ions is the major type of radiation found in space and is considered a potential health risk for astronauts. Even though the chance that these high LET particles traversing through the cytoplasm of cells is higher than that through the nuclei, the contribution of targeted cytoplasmic irradiation to the induction of genomic instability and other chromosomal damages induced by high LET radiation is not known. In the present study, we investigated whether mitochondria are the potential cytoplasmic target of high LET radiation in mediating cellular damage using a mitochondrial DNA (mtDNA) depleted (ρ0) human small airway epithelial (SAE) cell model and a precision charged particle microbeam with a beam width of merely one micron. Targeted cytoplasmic irradiation by high LET α particles induced DNA oxidative damage and double strand breaks in wild type ρ+ SAE cells. Furthermore, there was a significant increase in autophagy and micronuclei, which is an indication of genomic instability, together with the activation of nuclear factor kappa-B (NF-κB) and mitochondrial inducible nitric oxide synthase (iNOS) signaling pathways in ρ+ SAE cells. In contrast, ρ0 SAE cells exhibited a significantly lower response to these same endpoints examined after cytoplasmic irradiation with high LET α particles. The results indicate that mitochondria are essential in mediating cytoplasmic radiation induced genotoxic damage in mammalian cells. Furthermore, the findings may shed some light in the design of countermeasures for space radiation.

Electronic cigarette aerosols suppress cellular antioxidant defenses and induce significant oxidative DNA damage

PubMed Central

Ganapathy, Vengatesh; Manyanga, Jimmy; Brame, Lacy; McGuire, Dehra; Sadhasivam, Balaji; Floyd, Evan; Rubenstein, David A.; Ramachandran, Ilangovan; Wagener, Theodore

2017-01-01

Background Electronic cigarette (EC) aerosols contain unique compounds in addition to toxicants and carcinogens traditionally found in tobacco smoke. Studies are warranted to understand the public health risks of ECs. Objective The aim of this study was to determine the genotoxicity and the mechanisms induced by EC aerosol extracts on human oral and lung epithelial cells. Methods Cells were exposed to EC aerosol or mainstream smoke extracts and DNA damage was measured using the primer anchored DNA damage detection assay (q-PADDA) and 8-oxo-dG ELISA assay. Cell viability, reactive oxygen species (ROS) and total antioxidant capacity (TAC) were measured using standard methods. mRNA and protein expression were evaluated by RT-PCR and western blot, respectively. Results EC aerosol extracts induced DNA damage in a dose-dependent manner, but independently of nicotine concentration. Overall, EC aerosol extracts induced significantly less DNA damage than mainstream smoke extracts, as measured by q-PADDA. However, the levels of oxidative DNA damage, as indicated by the presence of 8-oxo-dG, a highly mutagenic DNA lesion, were similar or slightly higher after exposure to EC aerosol compared to mainstream smoke extracts. Mechanistically, while exposure to EC extracts significantly increased ROS, it decreased TAC as well as the expression of 8-oxoguanine DNA glycosylase (OGG1), an enzyme essential for the removal of oxidative DNA damage. Conclusions Exposure to EC aerosol extracts suppressed the cellular antioxidant defenses and led to significant DNA damage. These findings emphasize the urgent need to investigate the potential long-term cancer risk of exposure to EC aerosol for vapers and the general public. PMID:28542301

Investigation of possible fs-LASIK induced retinal damage

NASA Astrophysics Data System (ADS)

Schumacher, S.; Sander, M.; Stolte, A.; Doepke, C.; Baumgaertner, W.; Lubatschowski, H.

2006-02-01

Rapid development of new laser technologies enabled the application of ultra short lasers in refractive surgery. Focused ultra short laser pulses in near-infrared spectral range can generate a laser induced breakdown (LIB) in the cornea, which will disrupt the tissue. Cutting depth and position can be established by varying the laser focus. The fs-LASIK technique allows both flap and lenticule to be formed by using fs-pulses without the presence of any mechanical impact. During the cutting process not all of the pulse energy is deposited into the cornea; approximately half of the remaining energy propagates through the eye and reaches the retina. Though defocused, the transmitted energy can still induce damage to the retina due to absorption by the retinal pigment epithelium and the transfer of thermal energy to surrounding tissue. The fs-LASIK process was simulated with two laser systems; one continous-wave and one in the fs-regime. For the simulation the exposure time and focusing numerical aperature which defines the retinal spot size were varied. The Damage thresholds of the laser beam exposed eyes were determined in terms of ophthalmoscopic and histopathologic observations.

Extract from Armoracia rusticana and its flavonoid components protect human lymphocytes against oxidative damage induced by hydrogen peroxide.

PubMed

Gafrikova, Michala; Galova, Eliska; Sevcovicova, Andrea; Imreova, Petronela; Mucaji, Pavel; Miadokova, Eva

2014-03-14

DNA damage prevention is an important mechanism involved in cancer prevention by dietary compounds. Armoracia rusticana is cultivated mainly for its roots that are used in the human diet as a pungent spice. The roots represent rich sources of biologically active phytocompounds, which are beneficial for humans. In this study we investigated the modulation of H₂O₂ genotoxicity using the A. rusticana root aqueous extract (AE) and two flavonoids (kaempferol or quercetin). Human lymphocytes pre-treated with AE, kaempferol and quercetin were challenged with H₂O₂ and the DNA damage was assessed by the comet assay. At first we assessed a non-genotoxic concentration of AE and flavonoids, respectively. In lymphocytes challenged with H₂O₂ we proved that the 0.0025 mg·mL⁻¹ concentration of AE protected human DNA. It significantly reduced H₂O₂-induced oxidative damage (from 78% to 35.75%). Similarly, a non-genotoxic concentration of kaempferol (5 μg·mL⁻¹) significantly diminished oxidative DNA damage (from 83.3% to 19.4%), and the same concentration of quercetin also reduced the genotoxic effect of H₂O₂ (from 83.3% to 16.2%). We conclude that AE, kaempferol and quercetin probably act as antimutagens. The molecular mechanisms underlying their antimutagenic activity might be explained by their antioxidant properties.

Edaravone ameliorates compression-induced damage in rat nucleus pulposus cells.

PubMed

Lin, Hui; Ma, Xuan; Wang, Bai-Chuan; Zhao, Lei; Liu, Jian-Xiang; Pu, Fei-Fei; Hu, Yi-Qiang; Hu, Hong-Zhi; Shao, Zeng-Wu

2017-11-15

Edaravone is a strong free radical scavenger most used for treating acute ischemic stroke. In this study we investigated the protective effects and underlying mechanisms of edaravone on compression-induced damage in rat nucleus pulposus (NP) cells. Cell viability was determined using MTT assay methods. NP cell apoptosis was measured by Hoechst 33,258 staining and Annexin V/PI double staining. Intracellular reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and intracellular calcium ([Ca 2+ ] i ) were determined by fluorescent probes DCFH-DA, JC-1 and Fluo-3/AM, respectively. Apoptosis-related proteins (cleaved caspase-3, cytosolic cytochrome c, Bax and Bcl-2) and extracellular matrix proteins (aggrecan and collagen II) were analyzed by western blot. Edaravone attenuated the compression-induced decrease in viability of NP cells in a dose-dependent manner. 33,258 and Annexin V/PI double staining showed that edaravone protected NP cells from compression-induced apoptosis. Further studies confirmed that edaravone protected NP cells against compression-induced mitochondrial pathway of apoptosis by inhibiting overproduction of ROS, collapse of MMP and overload of [Ca 2+ ] i . In addition, edaravone promoted the expression of aggrecan and collagen II in compression-treated NP cells. These results strongly indicate that edaravone ameliorates compression-induced damage in rat nucleus pulposus cells. Edaravone could be a potential new drug for treatment of IDD. Copyright © 2017 Elsevier Inc. All rights reserved.

Tangeretin sensitizes SGS1-deficient cells by inducing DNA damage.

PubMed

Chong, Shin Yen; Wu, Meng-Ying; Lo, Yi-Chen

2013-07-03

Tangeretin, a polymethoxyflavone found in citrus peel, has been shown to have antiatherogenic, anti-inflammatory, and anticarcinogenic properties. However, the underlying target pathways are not fully characterized. We investigated the tangeretin sensitivity of yeast (Saccharomyces cerevisiae) mutants for DNA damage response or repair pathways. We found that tangeretin treatment significantly reduced (p < 0.05) survival rate, induced preferential G1 phase accumulation, and elevated the DNA double-strand break (DSB) signal γH2A in DNA repair-defective sgs1Δ cells, but had no obvious effects on wild-type cells or mutants of the DNA damage checkpoint (including tel1Δ, sml1Δ mec1Δ, sml1Δ mec1Δ tel1Δ, and rad9Δ mutants). Additionally, microarray data indicated that tangeretin treatment up-regulates genes involved in nutritional processing and down-regulates genes related to RNA processing in sgs1Δ mutants. These results suggest tangeretin may sensitize SGS1-deficient cells by increasing a marker of DNA damage and by inducing G1 arrest and possibly metabolic stress. Thus, tangeretin may be suitable for chemosensitization of cancer cells lacking DSB-repair ability.

Rapid communications: antiperspirant induced DNA damage in canine cells by comet assay.

PubMed

Yiu, Gloria

2004-01-01

Abstract Millions of people around the world use antiperspirants to decrease or eliminate body odors. Most antiperspirants contain aluminum zirconium or another form of aluminum as its active ingredient. The present investigation applied Comet assay to detect if Secret Platinum for women, Old Spice for men, or Crystal Natural produced DNA damage in Madin-Darby canine kidney cells (MDCKII). This study has shown that antiperspirants cause DNA damage on a single-cell level. Additionally, our data showed us that in general, Secret Platinum for women and Old Spice for men, produced equivalent damage. Crystal Natural, marketed as being safer or less damaging, induced the most extensive damage of all three antiperspirants tested.

Investigation on the correlation between energy deposition and clustered DNA damage induced by low-energy electrons.

PubMed

Liu, Wei; Tan, Zhenyu; Zhang, Liming; Champion, Christophe

2018-05-01

This study presents the correlation between energy deposition and clustered DNA damage, based on a Monte Carlo simulation of the spectrum of direct DNA damage induced by low-energy electrons including the dissociative electron attachment. Clustered DNA damage is classified as simple and complex in terms of the combination of single-strand breaks (SSBs) or double-strand breaks (DSBs) and adjacent base damage (BD). The results show that the energy depositions associated with about 90% of total clustered DNA damage are below 150 eV. The simple clustered DNA damage, which is constituted of the combination of SSBs and adjacent BD, is dominant, accounting for 90% of all clustered DNA damage, and the spectra of the energy depositions correlating with them are similar for different primary energies. One type of simple clustered DNA damage is the combination of a SSB and 1-5 BD, which is denoted as SSB + BD. The average contribution of SSB + BD to total simple clustered DNA damage reaches up to about 84% for the considered primary energies. In all forms of SSB + BD, the SSB + BD including only one base damage is dominant (above 80%). In addition, for the considered primary energies, there is no obvious difference between the average energy depositions for a fixed complexity of SSB + BD determined by the number of base damage, but average energy depositions increase with the complexity of SSB + BD. In the complex clustered DNA damage constituted by the combination of DSBs and BD around them, a relatively simple type is a DSB combining adjacent BD, marked as DSB + BD, and it is of substantial contribution (on average up to about 82%). The spectrum of DSB + BD is given mainly by the DSB in combination with different numbers of base damage, from 1 to 5. For the considered primary energies, the DSB combined with only one base damage contributes about 83% of total DSB + BD, and the average energy deposition is about 106 eV. However, the

A pathway of targeted autophagy is induced by DNA damage in budding yeast

PubMed Central

Eapen, Vinay V.; Waterman, David P.; Bernard, Amélie; Schiffmann, Nathan; Sayas, Enrich; Kamber, Roarke; Lemos, Brenda; Memisoglu, Gonen; Ang, Jessie; Mazella, Allison; Chuartzman, Silvia G.; Loewith, Robbie J.; Schuldiner, Maya; Denic, Vladimir; Klionsky, Daniel J.; Haber, James E.

2017-01-01

Autophagy plays a central role in the DNA damage response (DDR) by controlling the levels of various DNA repair and checkpoint proteins; however, how the DDR communicates with the autophagy pathway remains unknown. Using budding yeast, we demonstrate that global genotoxic damage or even a single unrepaired double-strand break (DSB) initiates a previously undescribed and selective pathway of autophagy that we term genotoxin-induced targeted autophagy (GTA). GTA requires the action primarily of Mec1/ATR and Rad53/CHEK2 checkpoint kinases, in part via transcriptional up-regulation of central autophagy proteins. GTA is distinct from starvation-induced autophagy. GTA requires Atg11, a central component of the selective autophagy machinery, but is different from previously described autophagy pathways. By screening a collection of ∼6,000 yeast mutants, we identified genes that control GTA but do not significantly affect rapamycin-induced autophagy. Overall, our findings establish a pathway of autophagy specific to the DNA damage response. PMID:28154131

A pathway of targeted autophagy is induced by DNA damage in budding yeast.

PubMed

Eapen, Vinay V; Waterman, David P; Bernard, Amélie; Schiffmann, Nathan; Sayas, Enrich; Kamber, Roarke; Lemos, Brenda; Memisoglu, Gonen; Ang, Jessie; Mazella, Allison; Chuartzman, Silvia G; Loewith, Robbie J; Schuldiner, Maya; Denic, Vladimir; Klionsky, Daniel J; Haber, James E

2017-02-14

Autophagy plays a central role in the DNA damage response (DDR) by controlling the levels of various DNA repair and checkpoint proteins; however, how the DDR communicates with the autophagy pathway remains unknown. Using budding yeast, we demonstrate that global genotoxic damage or even a single unrepaired double-strand break (DSB) initiates a previously undescribed and selective pathway of autophagy that we term genotoxin-induced targeted autophagy (GTA). GTA requires the action primarily of Mec1/ATR and Rad53/CHEK2 checkpoint kinases, in part via transcriptional up-regulation of central autophagy proteins. GTA is distinct from starvation-induced autophagy. GTA requires Atg11, a central component of the selective autophagy machinery, but is different from previously described autophagy pathways. By screening a collection of ∼6,000 yeast mutants, we identified genes that control GTA but do not significantly affect rapamycin-induced autophagy. Overall, our findings establish a pathway of autophagy specific to the DNA damage response.

Clustered DNA damages induced in human hematopoietic cells by low doses of ionizing radiation

NASA Technical Reports Server (NTRS)

Sutherland, Betsy M.; Bennett, Paula V.; Cintron-Torres, Nela; Hada, Megumi; Trunk, John; Monteleone, Denise; Sutherland, John C.; Laval, Jacques; Stanislaus, Marisha; Gewirtz, Alan

2002-01-01

Ionizing radiation induces clusters of DNA damages--oxidized bases, abasic sites and strand breaks--on opposing strands within a few helical turns. Such damages have been postulated to be difficult to repair, as are double strand breaks (one type of cluster). We have shown that low doses of low and high linear energy transfer (LET) radiation induce such damage clusters in human cells. In human cells, DSB are about 30% of the total of complex damages, and the levels of DSBs and oxidized pyrimidine clusters are similar. The dose responses for cluster induction in cells can be described by a linear relationship, implying that even low doses of ionizing radiation can produce clustered damages. Studies are in progress to determine whether clusters can be produced by mechanisms other than ionizing radiation, as well as the levels of various cluster types formed by low and high LET radiation.

Topical Application of Liposomal Antioxidant’s for Protection Against CEES Induced Skin Damage

DTIC Science & Technology

2006-07-01

14. ABSTRACT The objective of this study is to develop an effective prophylactic therapy against an analog of mustard gas, 2-chloroethylethyl...sulfide (CEES). The therapy for CEES-induced skin damage will be based on the topical application of antioxidant liposomes. We will use EpiDerm cultured...to develop an effective prophylactic therapy against CEES-induced skin damage (analogous to HD effect) based on the topical application of

Multiple pulse nanosecond laser induced damage threshold on hybrid mirrors

NASA Astrophysics Data System (ADS)

Vanda, Jan; Muresan, Mihai-George; Bilek, Vojtech; Sebek, Matej; Hanus, Martin; Lucianetti, Antonio; Rostohar, Danijela; Mocek, Tomas; Škoda, Václav

2017-11-01

So-called hybrid mirrors, consisting of broadband metallic surface coated with dielectric reflector designed for specific wavelength, becoming more important with progressing development of broadband mid-IR sources realized using parametric down conversion system. Multiple pulse nanosecond laser induced damage on such mirrors was tested by method s-on-1, where s stands for various numbers of pulses. We show difference in damage threshold between common protected silver mirrors and hybrid silver mirrors prepared by PVD technique and their variants prepared by IAD. Keywords: LIDT,

Long-term exposure to high air pollution induces cumulative DNA damages in traffic policemen.

PubMed

Tan, Chaochao; Lu, Shijie; Wang, Yupeng; Zhu, Yan; Shi, Ting; Lin, Mingyue; Deng, Zhonghua; Wang, Zhu; Song, Nana; Li, Shuna; Yang, Pingting; Yang, Liyan; Liu, Yuanyuan; Chen, Zhiheng; Xu, Keqian

2017-09-01

The specific effects of long-term exposure to high air pollution on human health and biological remain unclear. To explore the adverse health effects as well as biological mechanisms and biomarkers for durative exposure to air pollution, 183 traffic policemen and 88 office policemen were enrolled in this study. The concentration of PM2.5 in both the traffic and office policemen's working environments were obtained. Detailed personal questionnaires were completed and levels of inflammation, oxidative stress and DNA damage markers of all participants were analyzed in this study. The average PM2.5 concentration of the intersections of main roads and the offices of control group were 132.4±48.9μg/m 3 and 50.80±38.6μg/m 3 , respectively. The traffic policemen, who stably exposed to at least 2 times higher PM2.5 in their work area as compared with the control group, have a median average duration of 7.00years, and average cumulative intersection duty time reached 8030h. No statistically significant differences in the levels of inflammation markers were observed between the traffic and office policemen. However, the DNA damage markers in traffic policemen shared significant positive correlation with cumulative intersection duty time and higher than those in the office policemen. Multiple linear regression analysis demonstrated that the increase of cumulative intersection duty time by 1h per day for one year was associated with the increase in 8-hydroxy-20-deoxyguanosine of 0.329% (95% CI: 0.249% to 0.409%), tail DNA of 0.051% (95% CI: 0.041% to 0.061%), micronucleus frequency of 0.036‰ (95% CI: 0.03‰ to 0.043‰), and a decrease in glutathione of 0.482% (95% CI: -0.652% to -0.313%). These findings suggest that long-term exposure to high air pollution could induce cumulative DNA damages, supporting the hypothesis that durative exposure to air pollution is associated with an increased risk of cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

Role of platinum DNA damage-induced transcriptional inhibition in chemotherapy-induced neuronal atrophy and peripheral neurotoxicity.

PubMed

Yan, Fang; Liu, Johnson J; Ip, Virginia; Jamieson, Stephen M F; McKeage, Mark J

2015-12-01

Platinum-based anticancer drugs cause peripheral neurotoxicity by damaging sensory neurons within the dorsal root ganglia (DRG), but the mechanisms are incompletely understood. The roles of platinum DNA binding, transcription inhibition and altered cell size were investigated in primary cultures of rat DRG cells. Click chemistry quantitative fluorescence imaging of RNA-incorporated 5-ethynyluridine showed high, but wide ranging, global levels of transcription in individual neurons that correlated with their cell body size. Treatment with platinum drugs reduced neuronal transcription and cell body size to an extent that corresponded to the amount of preceding platinum DNA binding, but without any loss of neuronal cells. The effects of platinum drugs on neuronal transcription and cell body size were inhibited by blocking platinum DNA binding with sodium thiosulfate, and mimicked by treatment with a model transcriptional inhibitor, actinomycin D. In vivo oxaliplatin treatment depleted the total RNA content of DRG tissue concurrently with altering DRG neuronal size. These findings point to a mechanism of chemotherapy-induced peripheral neurotoxicity, whereby platinum DNA damage induces global transcriptional arrest leading in turn to neuronal atrophy. DRG neurons may be particularly vulnerable to this mechanism of toxicity because of their requirements for high basal levels of global transcriptional activity. Findings point to a new stepwise mechanism of chemotherapy-induced peripheral neurotoxicity, whereby platinum DNA damage induces global transcriptional arrest leading in turn to neuronal atrophy. Dorsal root ganglion neurons may be particularly vulnerable to this neurotoxicity because of their high global transcriptional outputs, demonstrated in this study by click chemistry quantitative fluorescence imaging. © 2015 International Society for Neurochemistry.

DNA DAMAGE QUANTITATION BY ALKALINE GEL ELECTROPHORESIS.

DOE Office of Scientific and Technical Information (OSTI.GOV)

SUTHERLAND,B.M.; BENNETT,P.V.; SUTHERLAND, J.C.

2004-03-24

Physical and chemical agents in the environment, those used in clinical applications, or encountered during recreational exposures to sunlight, induce damages in DNA. Understanding the biological impact of these agents requires quantitation of the levels of such damages in laboratory test systems as well as in field or clinical samples. Alkaline gel electrophoresis provides a sensitive (down to {approx} a few lesions/5Mb), rapid method of direct quantitation of a wide variety of DNA damages in nanogram quantities of non-radioactive DNAs from laboratory, field, or clinical specimens, including higher plants and animals. This method stems from velocity sedimentation studies of DNAmore » populations, and from the simple methods of agarose gel electrophoresis. Our laboratories have developed quantitative agarose gel methods, analytical descriptions of DNA migration during electrophoresis on agarose gels (1-6), and electronic imaging for accurate determinations of DNA mass (7-9). Although all these components improve sensitivity and throughput of large numbers of samples (7,8,10), a simple version using only standard molecular biology equipment allows routine analysis of DNA damages at moderate frequencies. We present here a description of the methods, as well as a brief description of the underlying principles, required for a simplified approach to quantitation of DNA damages by alkaline gel electrophoresis.« less

Bactericidal Antibiotics Induce Mitochondrial Dysfunction and Oxidative Damage in Mammalian Cells

PubMed Central

Costello, James C.; Liesa, Marc; Morones-Ramirez, J Ruben; Slomovic, Shimyn; Molina, Anthony; Shirihai, Orian S.; Collins, James J.

2013-01-01

Prolonged antibiotic treatment can lead to detrimental side effects in patients, including ototoxicity, nephrotoxicity, and tendinopathy, yet the mechanisms underlying the effects of antibiotics in mammalian systems remain unclear. It has been suggested that bactericidal antibiotics induce the formation of toxic reactive oxygen species (ROS) in bacteria. We show that clinically relevant doses of bactericidal antibiotics—quinolones, aminoglycosides, and β-lactams—cause mitochondrial dysfunction and ROS overproduction in mammalian cells. We demonstrate that these bactericidal antibiotic–induced effects lead to oxidative damage to DNA, proteins, and membrane lipids. Mice treated with bactericidal antibiotics exhibited elevated oxidative stress markers in the blood, oxidative tissue damage, and up-regulated expression of key genes involved in antioxidant defense mechanisms, which points to the potential physiological relevance of these antibiotic effects. The deleterious effects of bactericidal antibiotics were alleviated in cell culture and in mice by the administration of the antioxidant N-acetyl-L-cysteine or prevented by preferential use of bacteriostatic antibiotics. This work highlights the role of antibiotics in the production of oxidative tissue damage in mammalian cells and presents strategies to mitigate or prevent the resulting damage, with the goal of improving the safety of antibiotic treatment in people. PMID:23825301

Multifocal electroretinogram (MFERG) evaluation of laser-induced secondary damage in the non-human primate (NHP)

NASA Astrophysics Data System (ADS)

Zwick, Harry; Stuck, Bruce E.; Akers, A.; Edsall, Peter; DiCarlo, Cheryl D.; Lund, David J.

2005-04-01

Laser induced retinal damage may involve primary injury to the central retina and secondary damage, including intraretinal scar formation (IRSF) retinal traction (RT) and retinal nerve fiber layer injury (RNFL). We have evaluated these laser induced retinal pathologies with MFERG in non-human primates (NHPs) with a Veris (4.9) MFERG system 103 Hexagons, centered on the macula with non-scaled arrays and in one NHP with a 2-frame/M-step sequence to assess long term exposure effects within the RNFL. Chemical restraint was achieved using Ketamine stability HCL (10 mg/kg IM) and Propofol (0.5 mg-1.2/Kg/min via syringe pump). Peribulbar eye blocks were performed using 2% lidocain or a mixture of 2% Lidocain/Marcain (monitored ocular motility was less than 40 microns in retinal space). Primary and secondary damage effects were induced with either q-switched single pulse Neodymium (1064 nm, 1.0 mJ) or Argon CW (10 to 1000 msec, 10-150 mW). MFERG demonstrated capability to detect primary and secondary induced retinal damage in both 1st and 2nd order kernels. Primary and secondary damage in the central retina was often suppressed in amplitude and with longer latencies relative to the MFERG norm. Preliminary investigations in one NHP with Primary and secondary RNFL damage at 9 to 14 months showed recovery with non-scaled array one frame / M-step sequence but demonstrated significant abnormalities for a two frame/ M-step sequence. Utilization of advanced Veris recording parameters involving spatial and temporal manipulation of the stimulus parameters can improve detection of functional deficits induced by focal laser retinal injury.

Platelet-Derived Growth Factor-BB Lessens Light-Induced Rod Photoreceptor Damage in Mice.

PubMed

Takahashi, Kei; Shimazawa, Masamitsu; Izawa, Hiroshi; Inoue, Yuki; Kuse, Yoshiki; Hara, Hideaki

2017-12-01

Platelet-derived growth factor (PDGF)-BB is known to have neuroprotective effects against various neurodegenerative disorders. The purpose of this study was to determine whether PDGF-BB can be neuroprotective against light-induced photoreceptor damage in mice. Mice were exposed to 8000-lux luminance for 3 hours to induce phototoxicity. Two hours before light exposure, the experimental mice were injected with PDGF-BB intravitreally, and the control mice were injected with phosphate-buffered saline. The light-exposed PDGF-BB-injected mice and saline-injected mice were evaluated electroretinographically and histologically. The site and expression levels of PDGFR-β and PDGF-BB were determined by immunostaining and Western blotting, respectively. The effect of PDGF-BB on light-induced cone and rod photoreceptor damage was also evaluated in vitro in 661W cells, a murine cone photoreceptor cell line, and in primary retinal cell cultures. An intravitreal injection of PDGF-BB significantly reduced the decrease in the amplitudes of the electroretinograms (ERGs) and the thinning of the outer nuclear layer (ONL) induced by the light exposure. It also reduced the number of TUNEL-positive cells in the ONL. PDGFR-β was expressed in the rod outer segments (OSs) but not the cone OSs. The levels of PDGF-BB and PDGFR-β were decreased after light irradiation. In addition, PDGF-BB had protective effects against light-induced damage to cells of rod photoreceptors but had no effect on the 661W cells in vitro. These findings indicate that PDGF-BB reduces the degree of light-induced retinal damage by activating PDGFR-β in rod photoreceptors. These findings suggest that PDGF-BB could play a role in the prevention of degeneration in eyes susceptible to phototoxicity.

Enhanced susceptibility of ovaries from obese mice to 7,12-dimethylbenz[a]anthracene-induced DNA damage

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ganesan, Shanthi, E-mail: shanthig@iastate.edu; Nteeba, Jackson, E-mail: nteeba@iastate.edu; Keating, Aileen F., E-mail: akeating@iastate.edu

7,12-Dimethylbenz[a]anthracene (DMBA) depletes ovarian follicles and induces DNA damage in extra-ovarian tissues, thus, we investigated ovarian DMBA-induced DNA damage. Additionally, since obesity is associated with increased offspring birth defect incidence, we hypothesized that a DMBA-induced DNA damage response (DDR) is compromised in ovaries from obese females. Wild type (lean) non agouti (a/a) and KK.Cg-Ay/J heterozygote (obese) mice were dosed with sesame oil or DMBA (1 mg/kg; intraperitoneal injection) at 18 weeks of age, for 14 days. Total ovarian RNA and protein were isolated and abundance of Ataxia telangiectasia mutated (Atm), X-ray repair complementing defective repair in Chinese hamster cells 6more » (Xrcc6), breast cancer type 1 (Brca1), Rad 51 homolog (Rad51), poly [ADP-ribose] polymerase 1 (Parp1) and protein kinase, DNA-activated, catalytic polypeptide (Prkdc) were quantified by RT-PCR or Western blot. Phosphorylated histone H2AX (γH2AX) level was determined by Western blotting. Obesity decreased (P < 0.05) basal protein abundance of PRKDC and BRCA1 proteins but increased (P < 0.05) γH2AX and PARP1 proteins. Ovarian ATM, XRCC6, PRKDC, RAD51 and PARP1 proteins were increased (P < 0.05) by DMBA exposure in lean mice. A blunted DMBA-induced increase (P < 0.05) in XRCC6, PRKDC, RAD51 and BRCA1 was observed in ovaries from obese mice, relative to lean counterparts. Taken together, DMBA exposure induced γH2AX as well as the ovarian DDR, supporting that DMBA causes ovarian DNA damage. Additionally, ovarian DDR was partially attenuated in obese females raising concern that obesity may be an additive factor during chemical-induced ovotoxicity. - Highlights: • DMBA induces markers of ovarian DNA damage. • Obesity induces low level ovarian DNA damage. • DMBA-induced DNA repair response is altered by obesity.« less

Cryptococcus neoformans-induced macrophage lysosome damage crucially contributes to fungal virulence1

PubMed Central

Davis, Michael J.; Eastman, Alison J.; Qiu, Yafeng; Gregorka, Brian; Kozel, Thomas R.; Osterholzer, John J.; Curtis, Jeffrey L.; Swanson, Joel A.; Olszewski, Michal A.

2015-01-01

Upon ingestion by macrophages, Cryptococcus neoformans (Cn) can survive and replicate intracellularly unless the macrophages become classically activated. The mechanism enabling intracellular replication is not fully understood; neither are the mechanisms which allow classical activation to counteract replication. Cn-induced lysosome damage was observed in infected murine bone marrow-derived macrophages, increased with time and required yeast viability. To demonstrate lysosome damage in the infected host, we developed a novel flow-cytometric method for measuring lysosome damage. Increased lysosome damage was found in Cn-containing lung cells compared to Cn–free cells. Among Cn-containing myeloid cells, recently recruited cells displayed lower damage than resident cells, consistent with the protective role of recruited macrophages. The magnitude of lysosome damage correlated with increased Cn replication. Experimental induction of lysosome damage increased Cn replication. Activation of macrophages with IFN-γ abolished macrophage lysosome damage and enabled increased killing of Cn. We conclude that induction of lysosome damage is an important Cn survival strategy and that classical activation of host macrophages counters replication by preventing damage. Thus, therapeutic strategies which decrease lysosomal damage, or increase resistance to such damage, could be valuable in treating cryptococcal infections. PMID:25637026

A FLUORESCENCE BASED ASSAY FOR DNA DAMAGE INDUCED BY TOXIC INDUSTRIAL CHEMICALS

EPA Science Inventory

Numerous natural and man-made agents are continuously released into the environment due to human activity. Many of these agents cause irreversible damage to the normal biological functions leading to morbidity and mortality in the exposed organisms. The possibility of deliberat...

Plasma induced DNA damage: Comparison with the effects of ionizing radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lazović, S.; Maletić, D.; Puač, N.

2014-09-22

We use human primary fibroblasts for comparing plasma and gamma rays induced DNA damage. In both cases, DNA strand breaks occur, but of fundamentally different nature. Unlike gamma exposure, contact with plasma predominantly leads to single strand breaks and base-damages, while double strand breaks are mainly consequence of the cell repair mechanisms. Different cell signaling mechanisms are detected confirming this (ataxia telangiectasia mutated - ATM and ataxia telangiectasia and Rad3 related - ATR, respectively). The effective plasma doses can be tuned to match the typical therapeutic doses of 2 Gy. Tailoring the effective dose through plasma power and duration of themore » treatment enables safety precautions mainly by inducing apoptosis and consequently reduced frequency of micronuclei.« less

Triptolide-induced mitochondrial damage dysregulates fatty acid metabolism in mouse sertoli cells.

PubMed

Cheng, Yisen; Chen, Gaojian; Wang, Li; Kong, Jiamin; Pan, Ji; Xi, Yue; Shen, Feihai; Huang, Zhiying

2018-08-01

Triptolide is a major active ingredient of tripterygium glycosides, used for the therapy of immune and inflammatory diseases. However, its clinical applications are limited by severe male fertility toxicity associated with decreased sperm count, mobility and testicular injures. In this study, we determined that triptoide-induced mitochondrial dysfunction triggered reduction of lactate and dysregulation of fatty acid metabolism in mouse Sertoli cells. First, triptolide induced mitochondrial damage through the suppressing of proliferator-activated receptor coactivator-1 alpha (PGC-1α) activity and protein. Second, mitochondrial damage decreased lactate production and dysregulated fatty acid metabolism. Finally, mitochondrial dysfunction was initiated by the inhibition of sirtuin 1 (SIRT1) with the regulation of AMP-activated protein kinase (AMPK) in Sertoli cells after triptolide treatment. Meanwhile, triptolide induced mitochondrial fatty acid oxidation dysregulation by increasing AMPK phosphorylation. Taken together, we provide evidence that the mechanism of triptolide-induced testicular toxicity under mitochondrial injury may involve a metabolic change. Copyright © 2018 Elsevier B.V. All rights reserved.

Radiation-damage-induced phasing: a case study using UV irradiation with light-emitting diodes.

PubMed

de Sanctis, Daniele; Zubieta, Chloe; Felisaz, Franck; Caserotto, Hugo; Nanao, Max H

2016-03-01

Exposure to X-rays, high-intensity visible light or ultraviolet radiation results in alterations to protein structure such as the breakage of disulfide bonds, the loss of electron density at electron-rich centres and the movement of side chains. These specific changes can be exploited in order to obtain phase information. Here, a case study using insulin to illustrate each step of the radiation-damage-induced phasing (RIP) method is presented. Unlike a traditional X-ray-induced damage step, specific damage is introduced via ultraviolet light-emitting diodes (UV-LEDs). In contrast to UV lasers, UV-LEDs have the advantages of small size, low cost and relative ease of use.

Gender differences in alcohol-induced neurotoxicity and brain damage.

PubMed

Alfonso-Loeches, Silvia; Pascual, María; Guerri, Consuelo

2013-09-06

Considerable evidence has demonstrated that women are more vulnerable than men to the toxic effects of alcohol, although the results as to whether gender differences exist in ethanol-induced brain damage are contradictory. We have reported that ethanol, by activating the neuroimmune system and Toll-like receptors 4 (TLR4), can cause neuroinflammation and brain injury. However, whether there are gender differences in alcohol-induced neuroinflammation and brain injury are currently controversial. Using the brains of TLR4(+/+) and TLR4(-/-) (TLR4-KO) mice, we report that chronic ethanol treatment induces inflammatory mediators (iNOS and COX-2), cytokines (IL-1β, TNF-α), gliosis processes, caspase-3 activation and neuronal loss in the cerebral cortex of both female and male mice. Conversely, the levels of these parameters tend to be higher in female than in male mice. Using an in vivo imaging technique, our results further evidence that ethanol treatment triggers higher GFAP levels and lower MAP-2 levels in female than in male mice, suggesting a greater effect of ethanol-induced astrogliosis and less MAP-2(+) neurons in female than in male mice. Our results further confirm the pivotal role of TLR4 in alcohol-induced neuroinflammation and brain damage since the elimination of TLR4 protects the brain of males and females against the deleterious effects of ethanol. In short, the present findings demonstrate that, during the same period of ethanol treatment, females are more vulnerable than males to the neurotoxic/neuroinflammatory effects of ethanol, thus supporting the view that women are more susceptible than men to the medical consequences of alcohol abuse. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Reduction of arsenite-enhanced ultraviolet radiation-induced DNA damage by supplemental zinc

PubMed Central

Cooper, Karen L.; King, Brenee S.; Sandoval, Monica M.; Liu, Ke Jian; Hudson, Laurie G.

2013-01-01

Arsenic is a recognized human carcinogen and there is evidence that arsenic augments the carcinogenicity of DNA damaging agents such as ultraviolet radiation (UVR) thereby acting as a co-carcinogen. Inhibition of DNA repair is one proposed mechanism to account for the co-carcinogenic actions of arsenic. We and others find that arsenite interferes with the function of certain zinc finger DNA repair proteins. Furthermore, we reported that zinc reverses the effects of arsenite in cultured cells and a DNA repair target protein, poly (ADP-ribose) polymerase-1. In order to determine whether zinc ameliorates the effects of arsenite on UVR-induced DNA damage in human keratinocytes and in an in vivo model, normal human epidermal keratinocytes and SKH-1 hairless mice were exposed to arsenite, zinc or both before solar-simulated (ss) UVR exposure. Poly (ADP-ribose) polymerase activity, DNA damage and mutation frequencies at the hprt locus were measured in each treatment group in normal human keratinocytes. DNA damage was assessed in vivo by immunohistochemical staining of skin sections isolated from SKH-1 hairless mice. Cell-based findings demonstrate that ssUVR-induced DNA damage and mutagenesis are enhanced by arsenite, and supplemental zinc partially reverses the arsenite effect. In vivo studies confirm that zinc supplementation decreases arsenite-enhanced DNA damage in response to ssUVR exposure. From these data we can conclude that zinc offsets the impact of arsenic on ssUVR-stimulated DNA damage in cells and in vivo suggesting that zinc supplementation may provide a strategy to improve DNA repair capacity in arsenic exposed human populations. PMID:23523584

Tumor induced hepatic myeloid derived suppressor cells can cause moderate liver damage.

PubMed

Eggert, Tobias; Medina-Echeverz, José; Kapanadze, Tamar; Kruhlak, Michael J; Korangy, Firouzeh; Greten, Tim F

2014-01-01

Subcutaneous tumors induce the accumulation of myeloid derived suppressor cells (MDSC) not only in blood and spleens, but also in livers of these animals. Unexpectedly, we observed a moderate increase in serum transaminases in mice with EL4 subcutaneous tumors, which prompted us to study the relationship of hepatic MDSC accumulation and liver injury. MDSC were the predominant immune cell population expanding in livers of all subcutaneous tumor models investigated (RIL175, B16, EL4, CT26 and BNL), while liver injury was only observed in EL4 and B16 tumor-bearing mice. Elimination of hepatic MDSC in EL4 tumor-bearing mice using low dose 5-fluorouracil (5-FU) treatment reversed transaminase elevation and adoptive transfer of hepatic MDSC from B16 tumor-bearing mice caused transaminase elevation indicating a direct MDSC mediated effect. Surprisingly, hepatic MDSC from B16 tumor-bearing mice partially lost their damage-inducing potency when transferred into mice bearing non damage-inducing RIL175 tumors. Furthermore, MDSC expansion and MDSC-mediated liver injury further increased with growing tumor burden and was associated with different cytokines including GM-CSF, VEGF, interleukin-6, CCL2 and KC, depending on the tumor model used. In contrast to previous findings, which have implicated MDSC only in protection from T cell-mediated hepatitis, we show that tumor-induced hepatic MDSC themselves can cause moderate liver damage.

Tumor Induced Hepatic Myeloid Derived Suppressor Cells Can Cause Moderate Liver Damage

PubMed Central

Eggert, Tobias; Medina-Echeverz, José; Kapanadze, Tamar; Kruhlak, Michael J.; Korangy, Firouzeh; Greten, Tim F.

2014-01-01

Subcutaneous tumors induce the accumulation of myeloid derived suppressor cells (MDSC) not only in blood and spleens, but also in livers of these animals. Unexpectedly, we observed a moderate increase in serum transaminases in mice with EL4 subcutaneous tumors, which prompted us to study the relationship of hepatic MDSC accumulation and liver injury. MDSC were the predominant immune cell population expanding in livers of all subcutaneous tumor models investigated (RIL175, B16, EL4, CT26 and BNL), while liver injury was only observed in EL4 and B16 tumor-bearing mice. Elimination of hepatic MDSC in EL4 tumor-bearing mice using low dose 5-fluorouracil (5-FU) treatment reversed transaminase elevation and adoptive transfer of hepatic MDSC from B16 tumor-bearing mice caused transaminase elevation indicating a direct MDSC mediated effect. Surprisingly, hepatic MDSC from B16 tumor-bearing mice partially lost their damage-inducing potency when transferred into mice bearing non damage-inducing RIL175 tumors. Furthermore, MDSC expansion and MDSC-mediated liver injury further increased with growing tumor burden and was associated with different cytokines including GM-CSF, VEGF, interleukin-6, CCL2 and KC, depending on the tumor model used. In contrast to previous findings, which have implicated MDSC only in protection from T cell-mediated hepatitis, we show that tumor-induced hepatic MDSC themselves can cause moderate liver damage. PMID:25401795

Growth Inhibition and DNA Damage Induced by X-Phenols in Yeast: A Quantitative Structure–Activity Relationship Study

PubMed Central

2017-01-01

Phenolic compounds and their derivatives are ubiquitous constituents of numerous synthetic and natural chemicals that exist in the environment. Their toxicity is mostly attributed to their hydrophobicity and/or the formation of free radicals. In a continuation of the study of phenolic toxicity in a systematic manner, we have examined the biological responses of Saccharomyces cerevisiae to a series of mostly monosubstituted phenols utilizing a quantitative structure–activity relationship (QSAR) approach. The biological end points included a growth assay that determines the levels of growth inhibition induced by the phenols as well as a yeast deletion (DEL) assay that assesses the ability of X-phenols to induce DNA damage or DNA breaks. The QSAR analysis of cell growth patterns determined by IC50 and IC80 values indicates that toxicity is delineated by a hydrophobic, parabolic model. The DEL assay was then utilized to detect genomic deletions in yeast. The increase in the genotoxicity was enhanced by the electrophilicity of the phenolic substituents that were strong electron donors as well as by minimal hydrophobicity. The electrophilicities are represented by Brown’s sigma plus values that are a variant of the Hammett sigma constants. A few mutant strains of genes involved in DNA repair were separately exposed to 2,6-di-tert-butyl-4-methyl-phenol (BHT) and butylated hydroxy anisole (BHA). They were subsequently screened for growth phenotypes. BHA-induced growth defects in most of the DNA repair null mutant strains, whereas BHT was unresponsive. PMID:29302629

Laser-induced damage threshold of camera sensors and micro-opto-electro-mechanical systems

NASA Astrophysics Data System (ADS)

Schwarz, Bastian; Ritt, Gunnar; Körber, Michael; Eberle, Bernd

2016-10-01

The continuous development of laser systems towards more compact and efficient devices constitutes an increasing threat to electro-optical imaging sensors such as complementary metal-oxide-semiconductors (CMOS) and charge-coupled devices (CCD). These types of electronic sensors are used in day-to-day life but also in military or civil security applications. In camera systems dedicated to specific tasks, also micro-opto-electro-mechanical systems (MOEMS) like a digital micromirror device (DMD) are part of the optical setup. In such systems, the DMD can be located at an intermediate focal plane of the optics and it is also susceptible to laser damage. The goal of our work is to enhance the knowledge of damaging effects on such devices exposed to laser light. The experimental setup for the investigation of laser-induced damage is described in detail. As laser sources both pulsed lasers and continuous-wave (CW) lasers are used. The laser-induced damage threshold (LIDT) is determined by the single-shot method by increasing the pulse energy from pulse to pulse or in the case of CW-lasers, by increasing the laser power. Furthermore, we investigate the morphology of laser-induced damage patterns and the dependence of the number of destructed device elements on the laser pulse energy or laser power. In addition to the destruction of single pixels, we observe aftereffects like persisting dead columns or rows of pixels in the sensor image.

Sustained water-level changes caused by damage and compaction induced by teleseismic earthquakes

NASA Astrophysics Data System (ADS)

Shalev, Eyal; Kurzon, Ittai; Doan, Mai-Linh; Lyakhovsky, Vladimir

2016-07-01

Sustained water-level increase and decrease induced by distant earthquakes were observed in two wells, Gomè 1 and Meizar 1 in Israel. The Gomè 1 well is located within a damage zone of a major fault zone, and Meizar 1 is relatively far from a fault. The monitored pressure change in both wells shows significant water-level oscillations and sustained water-level changes in response to the passage of the seismic waves. The sustained water-level changes include short-term (minutes) undrained behavior and longer-period (hours and days) drained behavior associated with groundwater flow. We model the short-term undrained response of water pressure oscillations and sustained change to the distant 2013 Mw 7.7 Balochistan earthquake by nonlinear elastic behavior of damaged rocks, accounting for small wave-induced compaction and damage accumulation. We suggest that the rocks are close to failure in both locations and strain oscillations produced by the passing seismic waves periodically push the rock above the yield cap, creating compaction when volumetric strain increases and damage when shear strain increases. Compaction increases pore pressure, whereas damage accumulation decreases pore pressure by fracture dilation. The dominant process depends on the properties of the rock. For highly damaged rocks, dilatancy is dominant and a sustained pressure decrease is expected. For low-damage rocks, compaction is the dominant process creating sustained water-level increase. We calculate damage and porosity changes associated to the Balochistan earthquake in both wells and quantify damage accumulation and compaction during the passage of the seismic waves.

Nuclear DNA damage-triggered NLRP3 inflammasome activation promotes UVB-induced inflammatory responses in human keratinocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hasegawa, Tatsuya, E-mail: tatsuya.hasegawa@to.shiseido.co.jp; Nakashima, Masaya; Suzuki, Yoshiharu

Ultraviolet (UV) radiation in sunlight can result in DNA damage and an inflammatory reaction of the skin commonly known as sunburn, which in turn can lead to cutaneous tissue disorders. However, little has been known about how UV-induced DNA damage mediates the release of inflammatory mediators from keratinocytes. Here, we show that UVB radiation intensity-dependently increases NLRP3 gene expression and IL-1β production in human keratinocytes. Knockdown of NLRP3 with siRNA suppresses UVB-induced production of not only IL-1β, but also other inflammatory mediators, including IL-1α, IL-6, TNF-α, and PGE{sub 2}. In addition, inhibition of DNA damage repair by knockdown of XPA,more » which is a major component of the nucleotide excision repair system, causes accumulation of cyclobutane pyrimidine dimer (CPD) and activation of NLRP3 inflammasome. In vivo immunofluorescence analysis confirmed that NLRP3 expression is also elevated in UV-irradiated human epidermis. Overall, our findings indicate that UVB-induced DNA damage initiates NLRP3 inflammasome activation, leading to release of various inflammatory mediators from human keratinocytes. - Highlights: • UVB radiation induces NLRP3 inflammasome activation in human keratinocytes. • NLRP3 knockdown suppresses production of UVB-induced inflammatory mediators. • UVB-induced DNA damage triggers NLRP3 inflammasome activation. • NLRP3 expression in human epidermis is elevated in response to UV radiation.« less

TDP1 repairs nuclear and mitochondrial DNA damage induced by chain-terminating anticancer and antiviral nucleoside analogs

PubMed Central

Huang, Shar-yin N.; Murai, Junko; Dalla Rosa, Ilaria; Dexheimer, Thomas S.; Naumova, Alena; Gmeiner, William H.; Pommier, Yves

2013-01-01

Chain-terminating nucleoside analogs (CTNAs) that cause stalling or premature termination of DNA replication forks are widely used as anticancer and antiviral drugs. However, it is not well understood how cells repair the DNA damage induced by these drugs. Here, we reveal the importance of tyrosyl–DNA phosphodiesterase 1 (TDP1) in the repair of nuclear and mitochondrial DNA damage induced by CTNAs. On investigating the effects of four CTNAs—acyclovir (ACV), cytarabine (Ara-C), zidovudine (AZT) and zalcitabine (ddC)—we show that TDP1 is capable of removing the covalently linked corresponding CTNAs from DNA 3′-ends. We also show that Tdp1−/− cells are hypersensitive and accumulate more DNA damage when treated with ACV and Ara-C, implicating TDP1 in repairing CTNA-induced DNA damage. As AZT and ddC are known to cause mitochondrial dysfunction, we examined whether TDP1 repairs the mitochondrial DNA damage they induced. We find that AZT and ddC treatment leads to greater depletion of mitochondrial DNA in Tdp1−/− cells. Thus, TDP1 seems to be critical for repairing nuclear and mitochondrial DNA damage caused by CTNAs. PMID:23775789

Autophagy activation promotes removal of damaged mitochondria and protects against renal tubular injury induced by albumin overload.

PubMed

Tan, Jin; Wang, Miaohong; Song, Shuling; Miao, Yuyang; Zhang, Qiang

2018-01-10

Proteinuria (albuminuria) is an important cause of aggravating tubulointerstitial injury. Previous studies have shown that autophagy activation can alleviate renal tubular epithelial cell injury caused by urinary protein, but the mechanism is not clear. Here, we investigated the role of clearance of damaged mitochondria in this protective effect. We found that albumin overload induces a significant increase in turnover of LC3-II and decrease in p62 protein level in renal proximal tubular (HK-2) cells in vitro. Albumin overload also induces an increase in mitochondrial damage. ALC, a mitochondrial torpent, alleviates mitochondrial damage induced by albumin overload and also decreases autophagy, while mitochondrial damage revulsant CCCP further increases autophagy. Furthermore, pretreatment of HK-2 cells with rapamycin reduced the amount of damaged mitochondria and the level of apoptosis induced by albumin overload. In contrast, blocking autophagy with chloroquine exerted an opposite effect. Taken together, our results indicated autophagy activation promotes removal of damaged mitochondria and protects against renal tubular injury caused by albumin overload. This further confirms previous research that autophagy activation is an adaptive response in renal tubular epithelial cells after urinary protein overload.

Ginger Treatment Ameliorates Alcohol-induced Myocardial Damage by Suppression of Hyperlipidemia and Cardiac Biomarkers in Rats.

PubMed

Subbaiah, Ganjikunta Venkata; Mallikarjuna, Korivi; Shanmugam, Bhasha; Ravi, Sahukari; Taj, Patan Usnan; Reddy, Kesireddy Sathyavelu

2017-01-01

Alcohol-induced hyperlipidemia is positively correlated with cardiovascular diseases. Several herbal extracts have been reported to protect the cardiac injury and suppress the hyperlipidemia. However, the effect of ginger extracts on alcohol-induced hyperlipidemia and associated myocardial damage remains unclear. This study investigated the cardio-protective properties of ginger ethanolic extract (Gt) against alcohol-induced myocardial damage, and further distinguished the association between hyperlipidemia and occurrence of myocardial damage in rats. Twenty four Wistar male albino rats (250 ± 20 g) were divided into four groups including, Normal control (NC) (0.9% NaCl), Ginger treated (Gt) (200 mg/Kg b.w.), Alcohol treated (At) (20% of 6g/kg b.w. alcohol), and Alcohol along with Ginger treatment (At+Gt). In this study, lipid profiles such as fatty acids, triglycerides, total cholesterol, phospholipids, low density lipoprotein and high density lipoproteins, and cardiac biomarkers, including LDH, AST, CK-MB, cTn-T and cTn-I were examined in rats. Furthermore, histopathological studies were also conducted. We found that alcohol-induced myocardial damage was associated with increased lipid profile except high density lipoprotein in alcohol treated (20%, 6g/kg b.w.) rats compared with control. Ginger treatment significantly reduced the alcohol-induced lipid profiles except high density lipoproteins. Furthermore, elevated cardiac biomarkers activity with alcohol intoxication was substantially suppressed by ginger treatment. In addition, ginger treatment for 7-weeks significantly minimized the alcohol-induced myocardial damage. Our results concluded that ginger could protect alcohol-induced myocardial damage by suppression of hyperlipidemia and cardiac biomarkers. Ginger extract could alleviate the myocardial injury partially due to the suppression of circulating FFAs and TG levels.Increased circulating cholesterol, LDL and phospholipids with alcohol intake were

SIRT1 activation mediates heat-induced survival of UVB damaged Keratinocytes.

PubMed

Calapre, Leslie; Gray, Elin S; Kurdykowski, Sandrine; David, Anthony; Descargues, Pascal; Ziman, Mel

2017-06-10

Exposure to heat stress after UVB irradiation induces a reduction of apoptosis, resulting in survival of DNA damaged human keratinocytes. This heat-mediated evasion of apoptosis appears to be mediated by activation of SIRT1 and inactivation of p53 signalling. In this study, we assessed the role of SIRT1 in the inactivation of p53 signalling and impairment of DNA damage response in UVB plus heat exposed keratinocytes. Activation of SIRT1 after multiple UVB plus heat exposures resulted in increased p53 deacetylation at K382, which is known to affect its binding to specific target genes. Accordingly, we noted decreased apoptosis and down regulation of the p53 targeted pro-apoptotic gene BAX and the DNA repair genes ERCC1 and XPC after UVB plus heat treatments. In addition, UVB plus heat induced increased expression of the cell survival gene Survivin and the proliferation marker Ki67. Notably, keratinocytes exposed to UVB plus heat in the presence of the SIRT1 inhibitor, Ex-527, showed a similar phenotype to those exposed to UV alone; i.e. an increase in p53 acetylation, increased apoptosis and low levels of Survivin. This study demonstrate that heat-induced SIRT1 activation mediates survival of DNA damaged keratinocytes through deacetylation of p53 after exposure to UVB plus heat.

Calculation on spectrum of direct DNA damage induced by low-energy electrons including dissociative electron attachment.

PubMed

Liu, Wei; Tan, Zhenyu; Zhang, Liming; Champion, Christophe

2017-03-01

In this work, direct DNA damage induced by low-energy electrons (sub-keV) is simulated using a Monte Carlo method. The characteristics of the present simulation are to consider the new mechanism of DNA damage due to dissociative electron attachment (DEA) and to allow determining damage to specific bases (i.e., adenine, thymine, guanine, or cytosine). The electron track structure in liquid water is generated, based on the dielectric response model for describing electron inelastic scattering and on a free-parameter theoretical model and the NIST database for calculating electron elastic scattering. Ionization cross sections of DNA bases are used to generate base radicals, and available DEA cross sections of DNA components are applied for determining DNA-strand breaks and base damage induced by sub-ionization electrons. The electron elastic scattering from DNA components is simulated using cross sections from different theoretical calculations. The resulting yields of various strand breaks and base damage in cellular environment are given. Especially, the contributions of sub-ionization electrons to various strand breaks and base damage are quantitatively presented, and the correlation between complex clustered DNA damage and the corresponding damaged bases is explored. This work shows that the contribution of sub-ionization electrons to strand breaks is substantial, up to about 40-70%, and this contribution is mainly focused on single-strand break. In addition, the base damage induced by sub-ionization electrons contributes to about 20-40% of the total base damage, and there is an evident correlation between single-strand break and damaged base pair A-T.

Electron-beam induced damage in thin insulating films on compound semiconductors. M.S. Thesis, 1988

NASA Technical Reports Server (NTRS)

Pantic, Dragan M.

1989-01-01

Phosphorus rich plasma enhanced chemical vapor deposition (PECVD) of silicon nitride and silicon dioxide films on n-type indium phosphide (InP) substrates were exposed to electron-beam irradiation in the 5 to 40 keV range for the purpose of characterizing the damage induced in the dielectric. The electron-beam exposure was on the range of 10(exp -7) to 10(exp -3) C/sq cm. The damage to the devices was characterized by capacitance-voltage (C-V) measurements of the metal insulator semiconductor (MIS) capacitors. These results were compared to results obtained for radiation damage of thermal silicon dioxide on silicon (Si) MOS capacitors with similar exposures. The radiation induced damage in the PECVD silicon nitride films on InP was successfully annealed out in an hydrogen/nitrogen (H2/N2) ambient at 400 C for 15 min. The PECVD silicon dioxide films on InP had the least radiation damage, while the thermal silicon dioxide films on Si had the most radiation damage.

TRPM2 channels mediate acetaminophen-induced liver damage

PubMed Central

Kheradpezhouh, Ehsan; Ma, Linlin; Morphett, Arthur; Barritt, Greg J.; Rychkov, Grigori Y.

2014-01-01

Acetaminophen (paracetamol) is the most frequently used analgesic and antipyretic drug available over the counter. At the same time, acetaminophen overdose is the most common cause of acute liver failure and the leading cause of chronic liver damage requiring liver transplantation in developed countries. Acetaminophen overdose causes a multitude of interrelated biochemical reactions in hepatocytes including the formation of reactive oxygen species, deregulation of Ca2+ homeostasis, covalent modification and oxidation of proteins, lipid peroxidation, and DNA fragmentation. Although an increase in intracellular Ca2+ concentration in hepatocytes is a known consequence of acetaminophen overdose, its importance in acetaminophen-induced liver toxicity is not well understood, primarily due to lack of knowledge about the source of the Ca2+ rise. Here we report that the channel responsible for Ca2+ entry in hepatocytes in acetaminophen overdose is the Transient Receptor Potential Melanostatine 2 (TRPM2) cation channel. We show by whole-cell patch clamping that treatment of hepatocytes with acetaminophen results in activation of a cation current similar to that activated by H2O2 or the intracellular application of ADP ribose. siRNA-mediated knockdown of TRPM2 in hepatocytes inhibits activation of the current by either acetaminophen or H2O2. In TRPM2 knockout mice, acetaminophen-induced liver damage, assessed by the blood concentration of liver enzymes and liver histology, is significantly diminished compared with wild-type mice. The presented data strongly suggest that TRPM2 channels are essential in the mechanism of acetaminophen-induced hepatocellular death. PMID:24569808

Statistical study of single and multiple pulse laser-induced damage in glasses.

PubMed

Gallais, L; Natoli, J; Amra, C

2002-12-16

Single and multiple pulse laser damage studies are performed in Suprasil silica and BK-7 borosilicate glasses. Experiments are made in the bulk of materials at 1.064microm with nanosecond pulses, using an accurate and reliable measurement system. By means of a statistical study on laser damage probabilities, we demonstrate that the same nano-precursors could be involved in the multiple shot and single shot damage process. A damage mechanism with two stages is then proposed to explain the results. Firstly, a pre-damage process, corresponding to material changes at a microscopic level, leads the precursor to a state that can induce a one-pulse damage. And secondly a final damage occurs, with a mechanism identical to the single shot case. For each material, a law is found to predict the precursor life-time. We can then deduce the long term life of optical elements in high-power laser systems submitted to multipulse irradiation.

Expression Profile of DNA Damage Signaling Genes in Proton Exposed Mouse Brain

NASA Astrophysics Data System (ADS)

Ramesh, Govindarajan; Wu, Honglu

Exposure of living systems to radiation results in a wide assortment of lesions, the most signif-icant of is damage to genomic DNA which induce several cellular functions such as cell cycle arrest, repair, apoptosis etc. The radiation induced DNA damage investigation is one of the im-portant area in biology, but still the information available regarding the effects of proton is very limited. In this report, we investigated the differential gene expression pattern of DNA damage signaling genes particularly, damaged DNA binding, repair, cell cycle arrest, checkpoints and apoptosis using quantitative real-time RT-PCR array in proton exposed mouse brain tissues. The expression profiles showed significant changes in DNA damage related genes in 2Gy proton exposed mouse brain tissues as compared with control brain tissues. Furthermore, we also show that significantly increased levels of apoptotic related genes, caspase-3 and 8 activities in these cells, suggesting that in addition to differential expression of DNA damage genes, the alteration of apoptosis related genes may also contribute to the radiation induced DNA damage followed by programmed cell death. In summary, our findings suggest that proton exposed brain tissue undergo severe DNA damage which in turn destabilize the chromatin stability.

Inductively Coupled Plasma-Induced Electrical Damage on HgCdTe Etched Surface at Cryogenic Temperatures

NASA Astrophysics Data System (ADS)

Liu, L. F.; Chen, Y. Y.; Ye, Z. H.; Hu, X. N.; Ding, R. J.; He, L.

2018-03-01

Plasma etching is a powerful technique for transferring high-resolution lithographic patterns into HgCdTe material with low etch-induced damage, and it is important for fabricating small-pixel-size HgCdTe infrared focal plane array (IRFPA) detectors. P- to n-type conversion is known to occur during plasma etching of vacancy-doped HgCdTe; however, it is usually unwanted and its removal requires extra steps. Etching at cryogenic temperatures can reduce the etch-induced type conversion depth in HgCdTe via the electrical damage mechanism. Laser beam-induced current (LBIC) is a nondestructive photoelectric characterization technique which can provide information regarding the vertical and lateral electrical field distribution, such as defects and p-n junctions. In this work, inductively coupled plasma (ICP) etching of HgCdTe was implemented at cryogenic temperatures. For an Ar/CH4 (30:1 in SCCM) plasma with ICP input power of 1000 W and RF-coupled DC bias of ˜ 25 V, a HgCdTe sample was dry-etched at 123 K for 5 min using ICP. The sample was then processed to remove a thin layer of the plasma-etched region while maintaining a ladder-like damaged layer by continuously controlling the wet chemical etching time. Combining the ladder etching method and LBIC measurement, the ICP etching-induced electrical damage depth was measured and estimated to be about 20 nm. The results indicate that ICP etching at cryogenic temperatures can significantly suppress plasma etching-induced electrical damage, which is beneficial for defining HgCdTe mesa arrays.

Cold atmospheric-pressure plasma induces DNA-protein crosslinks through protein oxidation.

PubMed

Guo, Li; Zhao, Yiming; Liu, Dingxin; Liu, Zhichao; Chen, Chen; Xu, Ruobing; Tian, Miao; Wang, Xiaohua; Chen, Hailan; Kong, Michael G

2018-05-03

Reactive oxygen and nitrogen species (ROS and RNS) generated by cold atmospheric-pressure plasma could damage genomic DNA, although the precise type of these DNA damage induced by plasma are poorly characterized. Understanding plasma-induced DNA damage will help to elucidate the biological effect of plasma and guide the application of plasma in ROS-based therapy. In this study, it was shown that ROS and RNS generated by physical plasma could efficiently induce DNA-protein crosslinks (DPCs) in bacteria, yeast, and human cells. An in vitro assay showed that plasma treatment resulted in the formation of covalent DPCs by activating proteins to crosslink with DNA. Mass spectrometry and hydroperoxide analysis detected oxidation products induced by plasma. DPC formation were alleviated by singlet oxygen scavenger, demonstrating the importance of singlet oxygen in this process. These results suggested the roles of DPC formation in DNA damage induced by plasma, which could improve the understanding of the biological effect of plasma and help to develop a new strategy in plasma-based therapy including infection and cancer therapy.

DNA damage induced by boron neutron capture therapy is partially repaired by DNA ligase IV.

PubMed

Kondo, Natsuko; Sakurai, Yoshinori; Hirota, Yuki; Tanaka, Hiroki; Watanabe, Tsubasa; Nakagawa, Yosuke; Narabayashi, Masaru; Kinashi, Yuko; Miyatake, Shin-ichi; Hasegawa, Masatoshi; Suzuki, Minoru; Masunaga, Shin-ichiro; Ohnishi, Takeo; Ono, Koji

2016-03-01

Boron neutron capture therapy (BNCT) is a particle radiation therapy that involves the use of a thermal or epithermal neutron beam in combination with a boron ((10)B)-containing compound that specifically accumulates in tumor. (10)B captures neutrons and the resultant fission reaction produces an alpha ((4)He) particle and a recoiled lithium nucleus ((7)Li). These particles have the characteristics of high linear energy transfer (LET) radiation and therefore have marked biological effects. High-LET radiation is a potent inducer of DNA damage, specifically of DNA double-strand breaks (DSBs). The aim of the present study was to clarify the role of DNA ligase IV, a key player in the non-homologous end-joining repair pathway, in the repair of BNCT-induced DSBs. We analyzed the cellular sensitivity of the mouse embryonic fibroblast cell lines Lig4-/- p53-/- and Lig4+/+ p53-/- to irradiation using a thermal neutron beam in the presence or absence of (10)B-para-boronophenylalanine (BPA). The Lig4-/- p53-/- cell line had a higher sensitivity than the Lig4+/+ p53-/-cell line to irradiation with the beam alone or the beam in combination with BPA. In BNCT (with BPA), both cell lines exhibited a reduction of the 50 % survival dose (D 50) by a factor of 1.4 compared with gamma-ray and neutron mixed beam (without BPA). Although it was found that (10)B uptake was higher in the Lig4+/+ p53-/- than in the Lig4-/- p53-/- cell line, the latter showed higher sensitivity than the former, even when compared at an equivalent (10)B concentration. These results indicate that BNCT-induced DNA damage is partially repaired using DNA ligase IV.

Evaluation of radio-protective effect of melatonin on whole body irradiation induced liver tissue damage.

PubMed

Shirazi, Alireza; Mihandoost, Ehsan; Ghobadi, Ghazale; Mohseni, Mehran; Ghazi-Khansari, Mahmoud

2013-01-01

Ionizing radiation interacts with biological systems to induce excessive fluxes of free radicals that attack various cellular components. Melatonin has been shown to be a direct free radical scavenger and indirect antioxidant via its stimulatory actions on the antioxidant system.The aim of this study was to evaluate the antioxidant role of melatonin against radiation-induced oxidative injury to the rat liver after whole body irradiation. In this experimental study,thirty-two rats were divided into four groups. Group 1 was the control group, group 2 only received melatonin (30 mg/kg on the first day and 30 mg/kg on the following days), group 3 only received whole body gamma irradiation of 10 Gy, and group 4 received 30 mg/kg melatonin 30 minutes prior to radiation plus whole body irradiation of 10 Gy plus 30 mg/kg melatonin daily through intraperitoneal (IP) injection for three days after irradiation. Three days after irradiation, all rats were sacrificed and their livers were excised to measure the biochemical parameters malondialdehyde (MDA) and glutathione (GSH). Each data point represents mean ± standard error on the mean (SEM) of at least eight animals per group. A one-way analysis of variance (ANOVA) was performed to compare different groups, followed by Tukey's multiple comparison tests (p<0.05). The results demonstrated that whole body irradiation induced liver tissue damage by increasing MDA levels and decreasing GSH levels. Hepatic MDA levels in irradiated rats that were treated with melatonin (30 mg/kg) were significantly decreased, while GSH levels were significantly increased, when compared to either of the control groups or the melatonin only group. The data suggest that administration of melatonin before and after irradiation may reduce liver damage caused by gamma irradiation.

Ultrasonic Assessment of Impact-Induced Damage and Microcracking in Polymer Matrix Composites

NASA Technical Reports Server (NTRS)

Liaw, Benjamin; Villars, Esther; Delmont, Frantz; Bowles, Kenneth J. (Technical Monitor)

2001-01-01

The main objective of this NASA FAR project is to conduct ultrasonic assessment of impact-induced damage and microcracking in polymer matrix composites at various temperatures. It is believed that the proposed study of impact damage assessment on polymer matrix composites will benefit several NASA missions and current interests, such as ballistic impact testing of composite fan containment and high strain rate deformation modeling of polymer matrix composites. Impact-induced damage mechanisms in GLARE and ARALL fiber-metal laminates subject to instrumented drop-weight impacts at various temperatures were studied. GLARE and ARALL are hybrid composites made of alternating layers of aluminum and glass (for GLARE) and aramid- (for ARALL) fiber-reinforced epoxy. Damage in pure aluminum panels impacted by foreign objects was mainly characterized by large plastic deformation surrounding a deep penetration dent. On the other hand, plastic deformation in fiber-metal laminates was often not as severe although the penetration dent was still produced. The more stiff fiber-reinforced epoxy layers provided better bending rigidity; thus, enhancing impact damage tolerance. Severe cracking, however, occurred due to the use of these more brittle fiber-reinforced epoxy layers. Fracture patterns, e.g., crack length and delamination size, were greatly affected by the lay-up configuration rather than by the number of layers, which implies that thickness effect was not significant for the panels tested in this study. Immersion ultrasound techniques were then used to assess damages generated by instrumented drop-weight impacts onto these fiber-metal laminate panels as well as 6061-T6 aluminum/cast acrylic sandwich plates adhered by epoxy. Depending on several parameters, such as impact velocity, mass, temperature, laminate configuration, sandwich construction, etc., various types of impact damage were observed, including plastic deformation, radiating cracks emanating from the impact site

Aeroallergens Induce Reactive Oxygen Species Production and DNA Damage and Dampen Antioxidant Responses in Bronchial Epithelial Cells.

PubMed

Chan, Tze Khee; Tan, W S Daniel; Peh, Hong Yong; Wong, W S Fred

2017-07-01

Exposure to environmental allergens is a major risk factor for asthma development. Allergens possess proteolytic activity that is capable of disrupting the airway epithelium. Although there is increasing evidence pointing to asthma as an epithelial disease, the underlying mechanism that drives asthma has not been fully elucidated. In this study, we investigated the direct DNA damage potential of aeroallergens on human bronchial epithelial cells and elucidated the mechanisms mediating the damage. Human bronchial epithelial cells, BEAS-2B, directly exposed to house dust mites (HDM) resulted in enhanced DNA damage, as measured by the CometChip and the staining of DNA double-strand break marker, γH2AX. HDM stimulated cellular reactive oxygen species production, increased mitochondrial oxidative stress, and promoted nitrosative stress. Notably, expression of nuclear factor erythroid 2-related factor 2-dependent antioxidant genes was reduced immediately after HDM exposure, suggesting that HDM altered antioxidant responses. HDM exposure also reduced cell proliferation and induced cell death. Importantly, HDM-induced DNA damage can be prevented by the antioxidants glutathione and catalase, suggesting that HDM-induced reactive oxygen and nitrogen species can be neutralized by antioxidants. Mechanistic studies revealed that HDM-induced cellular injury is NADPH oxidase (NOX)-dependent, and apocynin, a NOX inhibitor, protected cells from double-strand breaks induced by HDM. Our results show that direct exposure of bronchial epithelial cells to HDM leads to the production of reactive oxygen and nitrogen species that damage DNA and induce cytotoxicity. Antioxidants and NOX inhibitors can prevent HDM-induced DNA damage, revealing a novel role for antioxidants and NOX inhibitors in mitigating allergic airway disease. Copyright © 2017 by The American Association of Immunologists, Inc.

Damage pattern as a function of radiation quality and other factors.

PubMed

Burkart, W; Jung, T; Frasch, G

1999-01-01

An understanding of damage pattern in critical cellular structures such as DNA is an important prerequisite for a mechanistic assessment of primary radiation damage, its possible repair, and the propagation of residual changes in somatic and germ cells as potential contributors to disease or ageing. Important quantitative insights have been made recently on the distribution in time and space of critical lesions from direct and indirect action of ionizing radiation on mammalian cells. When compared to damage from chemicals or from spontaneous degradation, e.g. depurination or base deamination in DNA, the potential of even low-LET radiation to create local hot spots of damage from single particle tracks is of utmost importance. This has important repercussions on inferences from critical biological effects at high dose and dose rate exposure situations to health risks at chronic, low-level exposures as experienced in environmental and controlled occupational settings. About 10,000 DNA lesions per human cell nucleus and day from spontaneous degradation and chemical attack cause no apparent effect, but a dose of 4 Gy translating into a similar number of direct and indirect DNA breaks induces acute lethality. Therefore, single lesions cannot explain the high efficiency of ionizing radiation in the induction of mutation, transformation and loss of proliferative capacity. Clustered damage leading to poorly repairable double-strand breaks or even more complex local DNA degradation, correlates better with fixed damage and critical biological endpoints. A comparison with other physical, chemical and biological agents indicates that ionizing radiation is indeed set apart from these by its unique micro- and nano-dosimetric traits. Only a few other agents such as bleomycin have a similar potential to cause complex damage from single events. However, in view of the multi-stage mechanism of carcinogenesis, it is still an open question whether dose-effect linearity for complex

Polymer-induced compression of biological hydrogels

NASA Astrophysics Data System (ADS)

Datta, Sujit; Preska Steinberg, Asher; Ismagilov, Rustem

Hydrogels - such as mucus, blood clots, and the extracellular matrix - provide critical functions in biological systems. However, little is known about how their structure is influenced by many of the polymeric materials they come into contact with regularly. Here, we focus on one critically important biological hydrogel: colonic mucus. While several biological processes are thought to potentially regulate the mucus hydrogel structure, the polymeric composition of the gut environment has been ignored. We use Flory-Huggins solution theory to characterize polymer-mucus interactions. We find that gut polymers, including those small enough to penetrate the mucus hydrogel, can in fact alter mucus structure, changing its equilibrium degree of swelling and forcing it to compress. The extent of compression increases with increasing polymer concentration and size. We use experiments on mice to verify these predictions with common dietary and therapeutic gut polymers. Our results provide a foundation for investigating similar, previously overlooked, polymer-induced effects in other biological hydrogels.

Nonlinear dynamics and damage induced properties of soft matter with application in oncology

NASA Astrophysics Data System (ADS)

Naimark, O.

2017-09-01

Molecular-morphological signs of oncogenesis could be linked to multiscale collective effects in molecular, cell and tissue related to defects (damage) dynamics. It was shown that nonlinear behavior of biological systems can be linked to the existence of characteristic collective open state modes providing the coherent expression dynamics. New type of criticality in nonequilibrium systems with defects—structural-scaling transition allows the definition of the `driving force' for a biological soft matter related to consolidated open states. The set of collective open states (breathers, autosolitons and blow-up modes) in the molecular ensembles provides the collective expression dynamics to attract the entire system (cell, tissue) toward a few preferred global states. The co-existence of three types of collective modes determines the multifractal scenario of biological soft matter dynamics. The appearance of `globally convergent' dynamics corresponding to the coherent behavior of multiscale blow-up open states (blow-up gene expression) leads to anomalous localized softening (blow-up localized damage) and the subjection of the cells (or tissue) to monofractal dynamics. This dynamics can be associated with cancer progression.

Wavelength dependence of femtosecond laser-induced damage threshold of optical materials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gallais, L., E-mail: laurent.gallais@fresnel.fr; Douti, D.-B.; Commandré, M.

2015-06-14

An experimental and numerical study of the laser-induced damage of the surface of optical material in the femtosecond regime is presented. The objective of this work is to investigate the different processes involved as a function of the ratio of photon to bandgap energies and compare the results to models based on nonlinear ionization processes. Experimentally, the laser-induced damage threshold of optical materials has been studied in a range of wavelengths from 1030 nm (1.2 eV) to 310 nm (4 eV) with pulse durations of 100 fs with the use of an optical parametric amplifier system. Semi-conductors and dielectrics materials, in bulk or thinmore » film forms, in a range of bandgap from 1 to 10 eV have been tested in order to investigate the scaling of the femtosecond laser damage threshold with the bandgap and photon energy. A model based on the Keldysh photo-ionization theory and the description of impact ionization by a multiple-rate-equation system is used to explain the dependence of laser-breakdown with the photon energy. The calculated damage fluence threshold is found to be consistent with experimental results. From these results, the relative importance of the ionization processes can be derived depending on material properties and irradiation conditions. Moreover, the observed damage morphologies can be described within the framework of the model by taking into account the dynamics of energy deposition with one dimensional propagation simulations in the excited material and thermodynamical considerations.« less

Does infrared or ultraviolet light damage the lens?

PubMed Central

Söderberg, P G; Talebizadeh, N; Yu, Z; Galichanin, K

2016-01-01

In daylight, the human eye is exposed to long wavelength ultraviolet radiation (UVR), visible radiation and short wavelength infrared radiation (IRR). Almost all the UVR and a fraction of the IRR waveband, respectively, left over after attenuation in the cornea, is absorbed in the lens. The time delay between exposure and onset of biological response in the lens varies from immediate-to-short-to-late. After exposure to sunlight or artificial sources, generating irradiances of the same order of magnitude or slightly higher, biological damage may occur photochemically or thermally. Epidemiological studies suggest a dose-dependent association between short wavelength UVR and cortical cataract. Experimental data infer that repeated daily in vivo exposures to short wavelength UVR generate photochemically induced damage in the lens, and that short delay onset cataract after UVR exposure is photochemically induced. Epidemiology suggests that daily high-intensity short wavelength IRR exposure of workers, is associated with a higher prevalence of age-related cataract. It cannot be excluded that this effect is owing to a thermally induced higher denaturation rate. Recent experimental data rule out a photochemical effect of 1090 nm in the lens but other wavelengths in the near IRR should be investigated. PMID:26768915

Black soybean seed coat polyphenols prevent AAPH-induced oxidative DNA-damage in HepG2 cells

PubMed Central

Yoshioka, Yasukiyo; Li, Xiu; Zhang, Tianshun; Mitani, Takakazu; Yasuda, Michiko; Nanba, Fumio; Toda, Toshiya; Yamashita, Yoko; Ashida, Hitoshi

2017-01-01

Black soybean seed coat extract (BE), which contains abundant polyphenols such as procyanidins, cyanidin 3-glucoside, (+)-catechin, and (−)­epicatechin, has been reported on health beneficial functions such as antioxidant activity, anti-inflammatory, anti-obesity, and anti-diabetic activities. In this study, we investigated that prevention of BE and its polyphenols on 2,2'-azobis(2-methylpropionamide) dihydrochloride (AAPH)-induced oxidative DNA damage, and found that these polyphenols inhibited AAPH-induced formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) as a biomarker for oxidative DNA damage in HepG2 cells. Under the same conditions, these polyphenols also inhibited AAPH-induced accumulation of reactive oxygen species (ROS) in the cells. Inhibition of ROS accumulation was observed in both cytosol and nucleus. It was confirmed that these polyphenols inhibited formation of AAPH radical using oxygen radical absorbance capacity assay under the cell-free conditions. These results indicate that polyphenols in BE inhibit free radical-induced oxidative DNA damages by their potent antioxidant activity. Thus, BE is an effective food material for prevention of oxidative stress and oxidative DNA damages. PMID:28366989

Non-destructive evaluation of UV pulse laser-induced damage performance of fused silica optics.

PubMed

Huang, Jin; Wang, Fengrui; Liu, Hongjie; Geng, Feng; Jiang, Xiaodong; Sun, Laixi; Ye, Xin; Li, Qingzhi; Wu, Weidong; Zheng, Wanguo; Sun, Dunlu

2017-11-24

The surface laser damage performance of fused silica optics is related to the distribution of surface defects. In this study, we used chemical etching assisted by ultrasound and magnetorheological finishing to modify defect distribution in a fused silica surface, resulting in fused silica samples with different laser damage performance. Non-destructive test methods such as UV laser-induced fluorescence imaging and photo-thermal deflection were used to characterize the surface defects that contribute to the absorption of UV laser radiation. Our results indicate that the two methods can quantitatively distinguish differences in the distribution of absorptive defects in fused silica samples subjected to different post-processing steps. The percentage of fluorescence defects and the weak absorption coefficient were strongly related to the damage threshold and damage density of fused silica optics, as confirmed by the correlation curves built from statistical analysis of experimental data. The results show that non-destructive evaluation methods such as laser-induced fluorescence and photo-thermal absorption can be effectively applied to estimate the damage performance of fused silica optics at 351 nm pulse laser radiation. This indirect evaluation method is effective for laser damage performance assessment of fused silica optics prior to utilization.

Can ebselen prevent cisplatin-induced ovarian damage?

PubMed

Soyman, Zeynep; Uzun, Hafize; Bayindir, Nihan; Esrefoglu, Mukaddes; Boran, Birtan

2018-06-01

The occurrence of ovarian damage is a major shortcoming in treating tumors with cisplatin (CP). The present study investigates the beneficial effects of ebselen-a seleno-organic compound with antioxidant and antiinflammatory properties-vis-à-vis CP-induced ovarian damage. Twenty-eight adult female rats were divided into four study groups. Group 1 received no treatment. The rats in Groups 2, 3, and 4 were intraperitoneally administered CP (2 mg/kg/day) twice per week, for 5 weeks. Those in Group 2 received 0.3 ml saline (0.9% NaCl) intraperitoneally 60 min before each CP treatment, while those in Group 3 received 0.2 ml dimethyl sulfoxide (DMSO) and 0.3 ml saline intraperitoneally 60 min before each CP treatment. The rats in Group 4 were pretreated with an intraperitoneal injection of 15 mg/kg/day ebselen 60 min before each CP treatment. Ovarian tissue malondialdehyde (MDA), total nitric oxide (NOx), glutathione (GSH), Cu/Zn-superoxide dismutase (Cu/Zn-SOD), and catalase levels, as well as histopathological damage scores (HDSs) and serum antimullerian hormone (AMH) levels, were assessed. Cu/Zn-SOD and GSH levels were significantly higher, and MDA and NOx levels significantly lower, in Group 4 than in Groups 2 and 3. Pretreatment with ebselen significantly improved serum AMH levels, relative to Groups 2 and 3. Additionally, HDS values were significantly lower in Group 4 than in Groups 2 and 3. Our results from using an experimental rat model of CP chemotherapy suggest that ebselen use may ameliorate ovarian damage by preventing oxidative injury.

A decrease in cyclin B1 levels leads to polyploidization in DNA damage-induced senescence.

PubMed

Kikuchi, Ikue; Nakayama, Yuji; Morinaga, Takao; Fukumoto, Yasunori; Yamaguchi, Naoto

2010-05-04

Adriamycin, an anthracycline antibiotic, has been used for the treatment of various types of tumours. Adriamycin induces at least two distinct types of growth repression, such as senescence and apoptosis, in a concentration-dependent manner. Cellular senescence is a condition in which cells are unable to proliferate further, and senescent cells frequently show polyploidy. Although abrogation of cell division is thought to correlate with polyploidization, the mechanisms underlying induction of polyploidization in senescent cells are largely unclear. We wished, therefore, to explore the role of cyclin B1 level in polyploidization of Adriamycin-induced senescent cells. A subcytotoxic concentration of Adriamycin induced polyploid cells having the features of senescence, such as flattened and enlarged cell shape and activated beta-galactosidase activity. In DNA damage-induced senescent cells, the levels of cyclin B1 were transiently increased and subsequently decreased. The decrease in cyclin B1 levels occurred in G2 cells during polyploidization upon treatment with a subcytotoxic concentration of Adriamycin. In contrast, neither polyploidy nor a decrease in cyclin B1 levels was induced by treatment with a cytotoxic concentration of Adriamycin. These results suggest that a decrease in cyclin B1 levels is induced by DNA damage, resulting in polyploidization in DNA damage-induced senescence.

Preliminary Results of Earthquake-Induced Building Damage Detection with Object-Based Image Classification

NASA Astrophysics Data System (ADS)

Sabuncu, A.; Uca Avci, Z. D.; Sunar, F.

2016-06-01

Earthquakes are the most destructive natural disasters, which result in massive loss of life, infrastructure damages and financial losses. Earthquake-induced building damage detection is a very important step after earthquakes since earthquake-induced building damage is one of the most critical threats to cities and countries in terms of the area of damage, rate of collapsed buildings, the damage grade near the epicenters and also building damage types for all constructions. Van-Ercis (Turkey) earthquake (Mw= 7.1) was occurred on October 23th, 2011; at 10:41 UTC (13:41 local time) centered at 38.75 N 43.36 E that places the epicenter about 30 kilometers northern part of the city of Van. It is recorded that, 604 people died and approximately 4000 buildings collapsed or seriously damaged by the earthquake. In this study, high-resolution satellite images of Van-Ercis, acquired by Quickbird-2 (Digital Globe Inc.) after the earthquake, were used to detect the debris areas using an object-based image classification. Two different land surfaces, having homogeneous and heterogeneous land covers, were selected as case study areas. As a first step of the object-based image processing, segmentation was applied with a convenient scale parameter and homogeneity criterion parameters. As a next step, condition based classification was used. In the final step of this preliminary study, outputs were compared with streetview/ortophotos for the verification and evaluation of the classification accuracy.

DETECTION OF LOW DOSE RADIATION INDUCED DNA DAMAGE USING TEMPERATURE DIFFERENTIAL FLUORESCENCE ASSAY

EPA Science Inventory

A rapid and sensitive fluorescence assay for radiation-induced DNA damage is reported. Changes in temperature-induced strand separation in both calf thymus DNA and plasmid DNA (puc 19 plasmid from Escherichia coli) were measured after exposure to low doses of radiation. Exposur...

DETECTION OF LOW DOSE RADIATION INDUCED DNA DAMAGE USING TEMPERATURE DIFFERENNTIAL FLUORESENCE ASSAY

EPA Science Inventory

A rapid and sensitive fluorescence assay for radiation-induced DNA damage is reported. Changes in temperature-induced strand separation in both calf thymus DNA and plasmid DNA (puc 19 plasmid from Escherichia coli) were measured after exposure to low doses of radiation. Exposures...

Gum acacia mitigates genetic damage in adenine-induced chronic renal failure in rats.

PubMed

Ali, B H; Al Balushi, K; Al-Husseini, I; Mandel, P; Nemmar, A; Schupp, N; Ribeiro, D A

2015-12-01

Subjects with chronic renal failure (CRF) exhibit oxidative genome damage, which may predispose to carcinogenesis, and Gum acacia (GumA) ameliorates this condition in humans and animals. We evaluated here renal DNA damage and urinary excretion of four nucleic acid oxidation adducts namely 8-oxoguanine (8-oxoGua), 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), 8-oxoguanosine (8-oxoGuo) and 8-hydroxy-2-deoxyguanisone (8-OHdg) in rats with adenine (ADE)-induced CRF with and without GumA treatment. Twenty-four rats were divided into four equal groups and treated for 4 weeks. The first group was given normal food and water (control). The second group was given normal food and GumA (15% w/v) in drinking water. The third group was fed powder diet containing adenine (ADE) (0·75% w/w in feed). The fourth group was fed like in the third group, plus GumA in drinking water (15%, w/v). ADE feeding induced CRF (as measured by several physiological, biochemical and histological indices) and also caused a significant genetic damage and significant decreases in urinary 8-oxo Gua and 8-oxoGuo, but not in the other nucleic acids. However, concomitant GumA treatment reduced the level of genetic damage in kidney cells as detected by Comet assay and significantly reversed the effect of adenine on urinary 8-oxoGuo. Treatment with GumA is able to mitigate genetic damage in renal tissues of rats with ADE-induced CRF. © 2015 Stichting European Society for Clinical Investigation Journal Foundation.

Reduction of hydrogen peroxide-induced erythrocyte damage by Carica papaya leaf extract.

PubMed

Okoko, Tebekeme; Ere, Diepreye

2012-06-01

To investigate the in vitro antioxidant potential of Carica papaya (C. papaya) leaf extract and its effect on hydrogen peroxide-induced erythrocyte damage assessed by haemolysis and lipid peroxidation. Hydroxyl radical scavenging activities, hydrogen ion scavenging activity, metal chelating activity, and the ferrous ion reducing ability were assessed as antioxidant indices. In the other experiment, human erythrocytes were treated with hydrogen peroxide to induce erythrocyte damage. The extract (at various concentrations) was subsequently incubated with the erythrocytes and later analysed for haemolysis and lipid peroxidation as indices for erythrocyte damage. Preliminary investigation of the extract showed that the leaf possessed significant antioxidant and free radical scavenging abilities using in vitro models in a concentration dependent manner (P<0.05). The extract also reduced hydrogen peroxide induced erythrocyte haemolysis and lipid peroxidation significantly when compared with ascorbic acid (P<0.05). The IC50 values were 7.33 mg/mL and 1.58 mg/mL for inhibition of haemolysis and lipid peroxidation, respectively. In all cases, ascorbic acid (the reference antioxidant) possessed higher activity than the extract. The findings show that C. papaya leaves possess significant bioactive potential which is attributed to the phytochemicals which act in synergy. Thus, the leaves can be exploited for pharmaceutical and nutritional purposes.

Edaravone protects human peripheral blood lymphocytes from γ-irradiation-induced apoptosis and DNA damage.

PubMed

Chen, Liming; Liu, Yinghui; Dong, Liangliang; Chu, Xiaoxia

2015-03-01

Radiation-induced cellular injury is attributed primarily to the harmful effects of free radicals, which play a key role in irradiation-induced apoptosis. In this study, we investigated the radioprotective efficacy of edaravone, a licensed clinical drug and a powerful free radical scavenger that has been tested against γ-irradiation-induced cellular damage in cultured human peripheral blood lymphocytes in studies of various diseases. Edaravone was pre-incubated with lymphocytes for 2 h prior to γ-irradiation. It was found that pretreatment with edaravone increased cell viability and inhibited generation of γ-radiation-induced reactive oxygen species (ROS) in lymphocytes exposed to 3 Gy γ-radiation. In addition, γ-radiation decreased antioxidant enzymatic activity, such as superoxide dismutase and glutathione peroxidase, as well as the level of reduced glutathione. Conversely, treatment with 100 μM edaravone prior to irradiation improved antioxidant enzyme activity and increased reduced glutathione levels in irradiated lymphocytes. Importantly, we also report that edaravone reduced γ-irradiation-induced apoptosis through downregulation of Bax, upregulation of Bcl-2, and consequent reduction of the Bax:Bcl-2 ratio. The current study shows edaravone to be an effective radioprotector against γ-irradiation-induced cellular damage in lymphocytes in vitro. Finally, edaravone pretreatment significantly reduced DNA damage in γ-irradiated lymphocytes, as measured by comet assay (% tail DNA, tail length, tail moment, and olive tail moment) (p < 0.05). Thus, the current study indicates that edaravone offers protection from radiation-induced cytogenetic alterations.

Characterization of photoactivated singlet oxygen damage in single-molecule optical trap experiments.

PubMed

Landry, Markita P; McCall, Patrick M; Qi, Zhi; Chemla, Yann R

2009-10-21

Optical traps or "tweezers" use high-power, near-infrared laser beams to manipulate and apply forces to biological systems, ranging from individual molecules to cells. Although previous studies have established that optical tweezers induce photodamage in live cells, the effects of trap irradiation have yet to be examined in vitro, at the single-molecule level. In this study, we investigate trap-induced damage in a simple system consisting of DNA molecules tethered between optically trapped polystyrene microspheres. We show that exposure to the trapping light affects the lifetime of the tethers, the efficiency with which they can be formed, and their structure. Moreover, we establish that these irreversible effects are caused by oxidative damage from singlet oxygen. This reactive state of molecular oxygen is generated locally by the optical traps in the presence of a sensitizer, which we identify as the trapped polystyrene microspheres. Trap-induced oxidative damage can be reduced greatly by working under anaerobic conditions, using additives that quench singlet oxygen, or trapping microspheres lacking the sensitizers necessary for singlet state photoexcitation. Our findings are relevant to a broad range of trap-based single-molecule experiments-the most common biological application of optical tweezers-and may guide the development of more robust experimental protocols.

Characterization of Photoactivated Singlet Oxygen Damage in Single-Molecule Optical Trap Experiments

PubMed Central

Landry, Markita P.; McCall, Patrick M.; Qi, Zhi; Chemla, Yann R.

2009-01-01

Abstract Optical traps or “tweezers” use high-power, near-infrared laser beams to manipulate and apply forces to biological systems, ranging from individual molecules to cells. Although previous studies have established that optical tweezers induce photodamage in live cells, the effects of trap irradiation have yet to be examined in vitro, at the single-molecule level. In this study, we investigate trap-induced damage in a simple system consisting of DNA molecules tethered between optically trapped polystyrene microspheres. We show that exposure to the trapping light affects the lifetime of the tethers, the efficiency with which they can be formed, and their structure. Moreover, we establish that these irreversible effects are caused by oxidative damage from singlet oxygen. This reactive state of molecular oxygen is generated locally by the optical traps in the presence of a sensitizer, which we identify as the trapped polystyrene microspheres. Trap-induced oxidative damage can be reduced greatly by working under anaerobic conditions, using additives that quench singlet oxygen, or trapping microspheres lacking the sensitizers necessary for singlet state photoexcitation. Our findings are relevant to a broad range of trap-based single-molecule experiments—the most common biological application of optical tweezers—and may guide the development of more robust experimental protocols. PMID:19843445

Laser-induced damage of coatings on Yb:YAG crystals at cryogenic condition

NASA Astrophysics Data System (ADS)

Wang, He; Zhang, Weili; Chen, Shunli; Zhu, Meiping; He, Hongbo; Fan, Zhengxiu

2011-12-01

As large amounts of heat need to be dissipated during laser operation, some diode pumped solid state lasers (DPSSL), especially Yb:YAG laser, operate at cryogenic condition. This work investigated the laser induced damage of coatings (high-reflective and anti-reflective coatings) on Yb:YAG crystals at cryogenic temperature and room temperature. The results show that the damage threshold of coatings at cryogenic temperature is lower than the one at room temperature. Field-emission scanning electron microscopy (FESEM), optical profiler, step profiler and Atomic force microscope (AFM) were used to obtain the damage morphology, size and depth. Taking alteration of physical parameters, microstructure of coatings and the environmental pollution into consideration, we analyzed the key factor of lowering the coating damage threshold at cryogenic conditions. The results are important to understand the mechanisms leading to damage at cryogenic condition.

Metabolic responses induced by DNA damage and poly (ADP-ribose) polymerase (PARP) inhibition in MCF-7 cells

PubMed Central

Bhute, Vijesh J.; Palecek, Sean P.

2015-01-01

Genomic instability is one of the hallmarks of cancer. Several chemotherapeutic drugs and radiotherapy induce DNA damage to prevent cancer cell replication. Cells in turn activate different DNA damage response (DDR) pathways to either repair the damage or induce cell death. These DDR pathways also elicit metabolic alterations which can play a significant role in the proper functioning of the cells. The understanding of these metabolic effects resulting from different types of DNA damage and repair mechanisms is currently lacking. In this study, we used NMR metabolomics to identify metabolic pathways which are altered in response to different DNA damaging agents. By comparing the metabolic responses in MCF-7 cells, we identified the activation of poly (ADP-ribose) polymerase (PARP) in methyl methanesulfonate (MMS)-induced DNA damage. PARP activation led to a significant depletion of NAD+. PARP inhibition using veliparib (ABT-888) was able to successfully restore the NAD+ levels in MMS-treated cells. In addition, double strand break induction by MMS and veliparib exhibited similar metabolic responses as zeocin, suggesting an application of metabolomics to classify the types of DNA damage responses. This prediction was validated by studying the metabolic responses elicited by radiation. Our findings indicate that cancer cell metabolic responses depend on the type of DNA damage responses and can also be used to classify the type of DNA damage. PMID:26478723

Gremlin inhibits UV-induced skin cell damages via activating VEGFR2-Nrf2 signaling

PubMed Central

Xu, Qiu-yun; Zhang, Jing; Lin, Meng-ting; Tu, Ying; He, Li; Bi, Zhi-gang; Cheng, Bo

2016-01-01

Ultra Violet (UV) radiation induces reactive oxygen species (ROS) production, DNA oxidation and single strand breaks (SSBs), which will eventually lead to skin cell damages or even skin cancer. Here, we tested the potential activity of gremlin, a novel vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2) agonist, against UV-induced skin cell damages. We show that gremlin activated VEGFR2 and significantly inhibited UV-induced death and apoptosis of skin keratinocytes and fibroblasts. Pharmacological inhibition or shRNA-mediated knockdown of VEGFR2 almost abolished gremlin-mediated cytoprotection against UV in the skin cells. Further studies showed that gremlin activated VEGFR2 downstream NF-E2-related factor 2 (Nrf2) signaling, which appeared required for subsequent skin cell protection. Nrf2 shRNA knockdown or S40T dominant negative mutation largely inhibited gremlin-mediated skin cell protection against UV. At last, we show that gremlin dramatically inhibited UV-induced ROS production and DNA SSB formation in skin keratinocytes and fibroblasts. We conclude that gremlin protects skin cells from UV damages via activating VEGFR2-Nrf2 signaling. Gremlin could be further tested as a novel anti-UV skin protectant. PMID:27713170

Gremlin inhibits UV-induced skin cell damages via activating VEGFR2-Nrf2 signaling.

PubMed

Ji, Chao; Huang, Jin-Wen; Xu, Qiu-Yun; Zhang, Jing; Lin, Meng-Ting; Tu, Ying; He, Li; Bi, Zhi-Gang; Cheng, Bo

2016-12-20

Ultra Violet (UV) radiation induces reactive oxygen species (ROS) production, DNA oxidation and single strand breaks (SSBs), which will eventually lead to skin cell damages or even skin cancer. Here, we tested the potential activity of gremlin, a novel vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2) agonist, against UV-induced skin cell damages. We show that gremlin activated VEGFR2 and significantly inhibited UV-induced death and apoptosis of skin keratinocytes and fibroblasts. Pharmacological inhibition or shRNA-mediated knockdown of VEGFR2 almost abolished gremlin-mediated cytoprotection against UV in the skin cells. Further studies showed that gremlin activated VEGFR2 downstream NF-E2-related factor 2 (Nrf2) signaling, which appeared required for subsequent skin cell protection. Nrf2 shRNA knockdown or S40T dominant negative mutation largely inhibited gremlin-mediated skin cell protection against UV. At last, we show that gremlin dramatically inhibited UV-induced ROS production and DNA SSB formation in skin keratinocytes and fibroblasts. We conclude that gremlin protects skin cells from UV damages via activating VEGFR2-Nrf2 signaling. Gremlin could be further tested as a novel anti-UV skin protectant.

Amifostine, a radioprotectant agent, protects rat brain tissue lipids against ionizing radiation induced damage: An FTIR microspectroscopic imaging study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cakmak G.; Miller L.; Zorlu, F.

2012-03-03

Amifostine is the only approved radioprotective agent by FDA for reducing the damaging effects of radiation on healthy tissues. In this study, the protective effect of amifostine against the damaging effects of ionizing radiation on the white matter (WM) and grey matter (GM) regions of the rat brain were investigated at molecular level. Sprague-Dawley rats, which were administered amifostine or not, were whole-body irradiated at a single dose of 800 cGy, decapitated after 24 h and the brain tissues of these rats were analyzed using Fourier transform infrared microspectroscopy (FTIRM). The results revealed that the total lipid content and CH{submore » 2} groups of lipids decreased significantly and the carbonyl esters, olefinic=CH and CH{sub 3} groups of lipids increased significantly in the WM and GM after exposure to ionizing radiation, which could be interpreted as a result of lipid peroxidation. These changes were more prominent in the WM of the brain. The administration of amifostine before ionizing radiation inhibited the radiation-induced lipid peroxidation in the brain. In addition, this study indicated that FTIRM provides a novel approach for monitoring ionizing radiation induced-lipid peroxidation and obtaining different molecular ratio images can be used as biomarkers to detect lipid peroxidation in biological systems.« less

Amifostine, a radioprotectant agent, protects rat brain tissue lipids against ionizing radiation induced damage: an FTIR microspectroscopic imaging study.

PubMed

Cakmak, Gulgun; Miller, Lisa M; Zorlu, Faruk; Severcan, Feride

2012-04-15

Amifostine is the only approved radioprotective agent by FDA for reducing the damaging effects of radiation on healthy tissues. In this study, the protective effect of amifostine against the damaging effects of ionizing radiation on the white matter (WM) and grey matter (GM) regions of the rat brain were investigated at molecular level. Sprague-Dawley rats, which were administered amifostine or not, were whole-body irradiated at a single dose of 800 cGy, decapitated after 24 h and the brain tissues of these rats were analyzed using Fourier transform infrared microspectroscopy (FTIRM). The results revealed that the total lipid content and CH(2) groups of lipids decreased significantly and the carbonyl esters, olefinic=CH and CH(3) groups of lipids increased significantly in the WM and GM after exposure to ionizing radiation, which could be interpreted as a result of lipid peroxidation. These changes were more prominent in the WM of the brain. The administration of amifostine before ionizing radiation inhibited the radiation-induced lipid peroxidation in the brain. In addition, this study indicated that FTIRM provides a novel approach for monitoring ionizing radiation induced-lipid peroxidation and obtaining different molecular ratio images can be used as biomarkers to detect lipid peroxidation in biological systems. Copyright © 2012 Elsevier Inc. All rights reserved.

Role of TRAIL and the pro-apoptotic Bcl-2 homolog Bim in acetaminophen-induced liver damage

PubMed Central

Badmann, A; Keough, A; Kaufmann, T; Bouillet, P; Brunner, T; Corazza, N

2011-01-01

Acetaminophen (N-acetyl-para-aminophenol (APAP), paracetamol) is a commonly used analgesic and antipyretic agent. Although considered safe at therapeutic doses, accidental or intentional overdose causes acute liver failure characterized by centrilobular hepatic necrosis with high morbidity and mortality. Although many molecular aspects of APAP-induced cell death have been described, no conclusive mechanism has been proposed. We recently identified TNF-related apoptosis-inducing ligand (TRAIL) and c-Jun kinase (JNK)-dependent activation of the pro-apoptotic Bcl-2 homolog Bim as an important apoptosis amplification pathway in hepatocytes. In this study, we, thus, investigated the role of TRAIL, c-JNK and Bim in APAP-induced liver damage. Our results demonstrate that TRAIL strongly synergizes with APAP in inducing cell death in hepatocyte-like cells lines and primary hepatocyte. Furthermore, we found that APAP strongly induces the expression of Bim in a c-JNK-dependent manner. Consequently, TRAIL- or Bim-deficient mice were substantially protected from APAP-induced liver damage. This study identifies the TRAIL-JNK-Bim axis as a novel target in the treatment of APAP-induced liver damage and substantiates its general role in hepatocyte death. PMID:21654829

Chemotherapy-induced damage to ovary: mechanisms and clinical impact.

PubMed

Bedoschi, Giuliano; Navarro, Paula Andrea; Oktay, Kutluk

2016-10-01

Cancer is a major public health problem around the world. Currently, about 5% of women diagnosed with cancer are of reproductive age. These young survivors may face compromised fertility. The effects of chemotherapeutic agents on ovarian reserve and its clinical consequences are generally inferred from a variety of surrogate markers of ovarian reserve, all aiming to provide prognostic information on fertility or the likelihood of success of infertility treatment. Until recently, the mechanisms that are responsible for chemotherapy-induced ovarian damage were not fully elucidated. The understanding of these mechanisms may lead to targeted treatments to preserve fertility. In this manuscript, we will review the current knowledge on the mechanism of ovarian damage and clinical impact of chemotherapy agents on fertility.

Role of interferon regulatory factor-1 in lipopolysaccharide-induced mitochondrial damage and oxidative stress responses in macrophages

PubMed Central

Deng, Song-Yun; Zhang, Le-Meng; Ai, Yu-hang; Pan, Pin-Hua; Zhao, Shuang-Ping; Su, Xiao-Li; Wu, Dong-Dong; Tan, Hong-Yi; Zhang, Li-Na; Tsung, Allan

2017-01-01

Sepsis causes many early deaths; both macrophage mitochondrial damage and oxidative stress responses are key factors in its pathogenesis. Although the exact mechanisms responsible for sepsis-induced mitochondrial damage are unknown, the nuclear transcription factor, interferon regulatory factor-1 (IRF-1) has been reported to cause mitochondrial damage in several diseases. Previously, we reported that in addition to promoting systemic inflammation, IRF-1 promoted the apoptosis of and inhibited autophagy in macrophages. In the present study, we hypothesized that lipopolysaccharide (LPS)-induced IRF-1 activation in macrophages may promote mitochondrial damage and oxidative stress. In vitro, LPS was found to promote IRF-1 activation, reactive oxygen species (ROS) production, adenosine triphosphate (ATP) depletion, superoxide dismutase (SOD) consumption, malondialdehyde (MDA) accumulation and mitochondrial depolarization in macrophages in a time- and dose-dependent manner. These effects were abrogated in cells in which IRF-1 was knocked down. Furthermore, IRF-1 overexpression increased LPS-induced oxidative stress responses and mitochondrial damage. In vivo, peritoneal macrophages obtained from IRF-1 knockout (KO) mice produced less ROS and had less mitochondrial depolarization and damage following the administration of LPS, when compared to their wild-type (WT) counterparts. In addition, IRF-1 KO mice exhibited a decreased release of mitochondrial DNA (mtDNA) following the administration of LPS. Thus, IRF-1 may be a critical factor in augmenting LPS-induced oxidative stress and mitochondrial damage in macrophages. PMID:28849179

Neuroprotective vaccination with copolymer-1 decreases laser-induced retinal damage

NASA Astrophysics Data System (ADS)

Belokopytov, Mark; Dubinsky, Galina; Belkin, Michael; Rosner, Mordechai

2003-06-01

The retinal damage induced by laser photocoagulation increases manifold by the secondary degeneration process whereby tissues adjacent to the primary lesion are destroyed. The neuroprotective effect of immunization by glatiramer acetate (Copolymer-1, Cop-1) in adjuvant was previously demonstrated in models of retina, optic nerve, brain, and spinal cord lesions. The present study tested the neuroprotective ability of Cop-1 to reduce the spread of laser-induced retinal damage. Standard argon laser lesions were created in 72 DA pigmented rats divided into four groups: two Cop-1 treated groups (animals treated seven days before or immediately after the laser session) and two control groups treated respectively by saline or the effective but toxic neuroprotective compound MK-801. The histological and morphological evaluations of the lesions 3, 20, and 60 days after the injury revealed significant reduction in photoreceptor loss of the retinas of the pre-immunized animals. Cop-1 given after the laser injury did not prevent cell loss significantly, while the neuroprotective effect of MK-801 was observed only on the third day after the laser injury. The results show that pre-immunization with Cop-1 is neuroprotective in unmyelinated (gray matter) neural tissue such as the retina. This approach may be of clinical significance in ameliorating laser-induced retinal injuries in humans.

DNA damage induced by Strontium-90 exposure at low concentrations in mesenchymal stromal cells: the functional consequences

PubMed Central

Musilli, S.; Nicolas, N.; El Ali, Z.; Orellana-Moreno, P.; Grand, C.; Tack, K.; Kerdine-Römer, S.; Bertho, J. M.

2017-01-01

90Sr is one of the radionuclides released after nuclear accidents that can significantly impact human health in the long term. 90Sr accumulates mostly in the bones of exposed populations. Previous research has shown that exposure induces changes in bone physiology both in humans and in mice. We hypothesize that, due to its close location with bone marrow stromal cells (BMSCs), 90Sr could induce functional damage to stromal cells that may explain these biological effects due to chronic exposure to 90Sr. The aim of this work was to verify this hypothesis through the use of an in vitro model of MS5 stromal cell lines exposed to 1 and 10 kBq.mL−1 of 90Sr. Results indicated that a 30-minute exposure to 90Sr induced double strand breaks in DNA, followed by DNA repair, senescence and differentiation. After 7 days of exposure, MS5 cells showed a decreased ability to proliferate, changes in cytokine expression, and changes in their ability to support hematopoietic progenitor proliferation and differentiation. These results demonstrate that chronic exposure to a low concentration of 90Sr can induce functional changes in BMSCs that in turn may explain the health effects observed in following chronic 90Sr exposure. PMID:28134299

DNA damage induced by Strontium-90 exposure at low concentrations in mesenchymal stromal cells: the functional consequences.

PubMed

Musilli, S; Nicolas, N; El Ali, Z; Orellana-Moreno, P; Grand, C; Tack, K; Kerdine-Römer, S; Bertho, J M

2017-01-30

90 Sr is one of the radionuclides released after nuclear accidents that can significantly impact human health in the long term. 90 Sr accumulates mostly in the bones of exposed populations. Previous research has shown that exposure induces changes in bone physiology both in humans and in mice. We hypothesize that, due to its close location with bone marrow stromal cells (BMSCs), 90 Sr could induce functional damage to stromal cells that may explain these biological effects due to chronic exposure to 90 Sr. The aim of this work was to verify this hypothesis through the use of an in vitro model of MS5 stromal cell lines exposed to 1 and 10 kBq.mL -1 of 90 Sr. Results indicated that a 30-minute exposure to 90 Sr induced double strand breaks in DNA, followed by DNA repair, senescence and differentiation. After 7 days of exposure, MS5 cells showed a decreased ability to proliferate, changes in cytokine expression, and changes in their ability to support hematopoietic progenitor proliferation and differentiation. These results demonstrate that chronic exposure to a low concentration of 90 Sr can induce functional changes in BMSCs that in turn may explain the health effects observed in following chronic 90 Sr exposure.

Damage induced in garnets by heavy ion irradiations: a study by optical spectroscopies

NASA Astrophysics Data System (ADS)

Costantini, Jean-Marc; Miro, Sandrine; Lelong, Gérald; Guillaumet, Maxime; Toulemonde, Marcel

2018-02-01

The damage induced by heavy-ion irradiation has been studied in yttrium iron garnet (Y3Fe5O12 or YIG) films, doped with Ca, Tb and Tm, grown by liquid-phase epitaxy on gadolinium gallium garnet (Gd3Ga5O12 or GGG) substrates. Irradiations of doped-YIG epitaxial films and GGG substrates with 36-MeV 183W and 12-MeV 197Au ions were applied for fluences between 1 × 1013 and 3 × 1015 cm-2 near room temperature. The radiation damage was monitored by micro-Raman spectroscopy and UV-visible optical absorption spectroscopy. Raman spectra revealed that amorphisation was achieved in YIG for both ions, whereas a high lattice disorder was induced in GGG without reaching amorphisation for the Au ion irradiation. Raman spectra also showed that a major damage of the tetrahedral sites was induced in GGG, as previously found for YIG. It is concluded that with such ions reaching the stopping power threshold of track formation in YIG and GGG the observed rate of amorphisation may result from a combination of electronic and nuclear energy losses as calculated using the unified thermal spike model.

The Effect of a Mars Mission on Chromosome Damage in the Blood Lymphocytes of Astronauts

NASA Technical Reports Server (NTRS)

George, Kerry A.; Durante, M.; Cucinnotta, F. A.

2006-01-01

The radiation environment encountered during a manned mission to Mars will lead to significant elevation of biological damage in astronauts. Here we present estimates of the increased frequencies of chromosome aberrations in the peripheral blood lymphocytes of astronauts after a hypothetical Mars mission using radiation dose estimations and lymphocyte biology. Results will incorporate previously published data on in vivo induced chromosome damage in the blood lymphocytes of crewmembers after ISS and Mir missions, along with recent findings on the time dependant decay of chromosome aberrations after space flight.

Antioxidant protective effect of honey in cigarette smoke-induced testicular damage in rats.

PubMed

Mohamed, Mahaneem; Sulaiman, Siti Amrah; Jaafar, Hasnan; Sirajudeen, Kuttulebbai Nainamohamed Salam

2011-01-01

Cigarette smoke (CS) can cause testicular damage and we investigated the possible protective effect of honey against CS-induced testicular damage and oxidative stress in rats. CS exposure (8 min, 3 times daily) and honey supplementation (1.2 g/kg daily) were given for 13 weeks. Rats exposed to CS significantly had smaller seminiferous tubules diameter and epithelial height, lower Leydig cell count and increased percentage of tubules with germ cell loss. CS also produced increased lipid peroxidation (TBARS) and glutathione peroxidase (GPx) activity, as well as reduced total antioxidant status (TAS) and activities of superoxide dismutase (SOD) and catalase (CAT). However, supplementation of honey significantly reduced histological changes and TBARS level, increased TAS level, as well as significantly restored activities of GPx, SOD and CAT in rat testis. These findings may suggest that honey has a protective effect against damage and oxidative stress induced by CS in rat testis.

Organophosphates induce distal axonal damage, but not brain oedema, by inactivating neuropathy target esterase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Read, David J.; Li Yong; Chao, Moses V.

2010-05-15

Single doses of organophosphorus compounds (OP) which covalently inhibit neuropathy target esterase (NTE) can induce lower-limb paralysis and distal damage in long nerve axons. Clinical signs of neuropathy are evident 3 weeks post-OP dose in humans, cats and chickens. By contrast, clinical neuropathy in mice following acute dosing with OPs or any other toxic compound has never been reported. Moreover, dosing mice with ethyloctylphosphonofluoridate (EOPF) - an extremely potent NTE inhibitor - causes a different (subacute) neurotoxicity with brain oedema. These observations have raised the possibility that mice are intrinsically resistant to neuropathies induced by acute toxic insult, but maymore » incur brain oedema, rather than distal axonal damage, when NTE is inactivated. Here we provide the first report that hind-limb dysfunction and extensive axonal damage can occur in mice 3 weeks after acute dosing with a toxic compound, bromophenylacetylurea. Three weeks after acutely dosing mice with neuropathic OPs no clinical signs were observed, but distal lesions were present in the longest spinal sensory axons. Similar lesions were evident in undosed nestin-cre:NTEfl/fl mice in which NTE had been genetically-deleted from neural tissue. The extent of OP-induced axonal damage in mice was related to the duration of NTE inactivation and, as reported in chickens, was promoted by post-dosing with phenylmethanesulfonylfluoride. However, phenyldipentylphosphinate, another promoting compound in chickens, itself induced in mice lesions different from the neuropathic OP type. Finally, EOPF induced subacute neurotoxicity with brain oedema in both wild-type and nestin-cre:NTEfl/fl mice indicating that the molecular target for this effect is not neural NTE.« less

Laser-Induced Damage Threshold and Certification Procedures for Optical Materials

NASA Technical Reports Server (NTRS)

1997-01-01

This document provides instructions for performing laser-induced-damage-threshold tests and pass-fail certification tests on optical materials used in pulsed-laser systems. The optical materials to which these procedures apply include coated and uncoated optical substrates, laser crystals, Q-switches, polarizers, and other optical components employed in pulsed-laser systems.

RNA protects a nucleoprotein complex against radiation damage.

PubMed

Bury, Charles S; McGeehan, John E; Antson, Alfred A; Carmichael, Ian; Gerstel, Markus; Shevtsov, Mikhail B; Garman, Elspeth F

2016-05-01

Radiation damage during macromolecular X-ray crystallographic data collection is still the main impediment for many macromolecular structure determinations. Even when an eventual model results from the crystallographic pipeline, the manifestations of radiation-induced structural and conformation changes, the so-called specific damage, within crystalline macromolecules can lead to false interpretations of biological mechanisms. Although this has been well characterized within protein crystals, far less is known about specific damage effects within the larger class of nucleoprotein complexes. Here, a methodology has been developed whereby per-atom density changes could be quantified with increasing dose over a wide (1.3-25.0 MGy) range and at higher resolution (1.98 Å) than the previous systematic specific damage study on a protein-DNA complex. Specific damage manifestations were determined within the large trp RNA-binding attenuation protein (TRAP) bound to a single-stranded RNA that forms a belt around the protein. Over a large dose range, the RNA was found to be far less susceptible to radiation-induced chemical changes than the protein. The availability of two TRAP molecules in the asymmetric unit, of which only one contained bound RNA, allowed a controlled investigation into the exact role of RNA binding in protein specific damage susceptibility. The 11-fold symmetry within each TRAP ring permitted statistically significant analysis of the Glu and Asp damage patterns, with RNA binding unexpectedly being observed to protect these otherwise highly sensitive residues within the 11 RNA-binding pockets distributed around the outside of the protein molecule. Additionally, the method enabled a quantification of the reduction in radiation-induced Lys and Phe disordering upon RNA binding directly from the electron density.

Rebamipide does not protect against naproxen-induced gastric damage: a randomized double-blind controlled trial.

PubMed

Gagliano-Jucá, Thiago; Moreno, Ronilson A; Zaminelli, Tiago; Napolitano, Mauro; Magalhães, Antônio Frederico N; Carvalhaes, Aloísio; Trevisan, Miriam S; Wallace, John L; De Nucci, Gilberto

2016-06-04

Rebamipide is a gastroprotective agent with promising results against gastric damage induced by non-steroidal anti-inflammatory drugs. The present study evaluated if rebamipide protects against naproxen-induced gastric damage in healthy volunteers. Changes in gastric PGE2 tissue concentration were also evaluated. After a preliminary endoscopy to rule out previous gastric macroscopic damage, twenty-four healthy volunteers of both sexes were divided into 2 groups. One group received sodium naproxen 550 mg b.i.d. plus placebo for 7 days, while the other group received sodium naproxen 550 mg b.i.d. plus rebamipide 100 mg b.i.d. At the end of treatment, a new endoscopy was performed. Gastric macroscopic damage was evaluated by the Cryer score and by the modified Lanza score. The primary outcome measure of the trial was the macroscopic damage observed in each treatment group at the end of treatment. Biopsies were collected at both endoscopies for PGE2 quantification and histopathological analysis (secondary outcomes). Tissue PGE2 was quantified by ELISA. The randomization sequence was generated using 3 blocks of 8 subjects each. Volunteers and endoscopists were blind to whether they were receiving rebamipide or placebo. All recruited volunteers completed the trial. Sodium naproxen induced gastric damage in both groups. At the end of the study, median Cryer score was 4 in both groups (Difference = 0; 95%CI = -1 to 0; p = 0.728). In the placebo group, the mean tissue PGE2 concentration was 1005 ± 129 pg/mL before treatment and 241 ± 41 pg/mL after treatment (p < 0.001). In the rebamipide group, the mean tissue PGE2 concentration was 999 ± 109 pg/mL before treatment, and 168 ± 13 pg/mL after treatment (p < 0.001). There was no difference in mean tissue PGE2 between the two groups (difference = 5; 95%CI from -334.870 to 345.650; p = 0.975). No significant change was observed at the histopathological evaluation, despite

Oxidative stress and DNA damage induced by imidacloprid in zebrafish (Danio rerio).

PubMed

Ge, Weili; Yan, Saihong; Wang, Jinhua; Zhu, Lusheng; Chen, Aimei; Wang, Jun

2015-02-18

Imidacloprid is a neonicotinoid insecticide that can have negative effects on nontarget animals. The present study was conducted to assess the toxicity of various imidacloprid doses (0.3, 1.25, and 5 mg/mL) on zebrafish sampled after 7, 14, 21, and 28 days of exposure. The levels of catalase (CAT), superoxide dismutase (SOD), reactive oxygen species (ROS), glutathione-S-transferase (GST), and malondialdehyde (MDA) and the extent of DNA damage were measured to evaluate the toxicity of imidacloprid on zebrafish. SOD and GST activities were noticeably increased during early exposure but were inhibited toward the end of the exposure period. In addition, the CAT levels decreased to the control level following their elevation during early exposure. High concentrations of imidacloprid (1.25 and 5 mg/L) induced excessive ROS production and markedly increased MDA content on the 21st day of exposure. DNA damage was dose- and time-dependent. In conclusion, the present study showed that imidacloprid can induce oxidative stress and DNA damage in zebrafish.

Buckwheat Honey Attenuates Carbon Tetrachloride-Induced Liver and DNA Damage in Mice

PubMed Central

Cheng, Ni; Wu, Liming; Zheng, Jianbin; Cao, Wei

2015-01-01

Buckwheat honey, which is widely consumed in China, has a characteristic dark color. The objective of this study was to investigate the protective effects of buckwheat honey on liver and DNA damage induced by carbon tetrachloride in mice. The results revealed that buckwheat honey had high total phenolic content, and rutin, hesperetin, and p-coumaric acid were the main phenolic compounds present. Buckwheat honey possesses super DPPH radical scavenging activity and strong ferric reducing antioxidant power. Administration of buckwheat honey for 10 weeks significantly inhibited serum lipoprotein oxidation and increased serum oxygen radical absorbance capacity. Moreover, buckwheat honey significantly inhibited aspartate aminotransferase and alanine aminotransferase activities, which are enhanced by carbon tetrachloride. Hepatic malondialdehyde decreased and hepatic antioxidant enzymes (superoxide dismutase and glutathione peroxidase) increased in the presence of buckwheat honey. In a comet assay, lymphocyte DNA damage induced by carbon tetrachloride was significantly inhibited by buckwheat honey. Therefore, buckwheat honey has a hepatoprotective effect and inhibits DNA damage, activities that are primarily attributable to its high antioxidant capacity. PMID:26508989

Buckwheat Honey Attenuates Carbon Tetrachloride-Induced Liver and DNA Damage in Mice.

PubMed

Cheng, Ni; Wu, Liming; Zheng, Jianbin; Cao, Wei

2015-01-01

Buckwheat honey, which is widely consumed in China, has a characteristic dark color. The objective of this study was to investigate the protective effects of buckwheat honey on liver and DNA damage induced by carbon tetrachloride in mice. The results revealed that buckwheat honey had high total phenolic content, and rutin, hesperetin, and p-coumaric acid were the main phenolic compounds present. Buckwheat honey possesses super DPPH radical scavenging activity and strong ferric reducing antioxidant power. Administration of buckwheat honey for 10 weeks significantly inhibited serum lipoprotein oxidation and increased serum oxygen radical absorbance capacity. Moreover, buckwheat honey significantly inhibited aspartate aminotransferase and alanine aminotransferase activities, which are enhanced by carbon tetrachloride. Hepatic malondialdehyde decreased and hepatic antioxidant enzymes (superoxide dismutase and glutathione peroxidase) increased in the presence of buckwheat honey. In a comet assay, lymphocyte DNA damage induced by carbon tetrachloride was significantly inhibited by buckwheat honey. Therefore, buckwheat honey has a hepatoprotective effect and inhibits DNA damage, activities that are primarily attributable to its high antioxidant capacity.

Numerical Analyses of the Influence of Blast-Induced Damaged Rock Around Shallow Tunnels in Brittle Rock

NASA Astrophysics Data System (ADS)

Saiang, David; Nordlund, Erling

2009-06-01

Most of the railway tunnels in Sweden are shallow-seated (<20 m of rock cover) and are located in hard brittle rock masses. The majority of these tunnels are excavated by drilling and blasting, which, consequently, result in the development of a blast-induced damaged zone around the tunnel boundary. Theoretically, the presence of this zone, with its reduced strength and stiffness, will affect the overall performance of the tunnel, as well as its construction and maintenance. The Swedish Railroad Administration, therefore, uses a set of guidelines based on peak particle velocity models and perimeter blasting to regulate the extent of damage due to blasting. However, the real effects of the damage caused by blasting around a shallow tunnel and their criticality to the overall performance of the tunnel are yet to be quantified and, therefore, remain the subject of research and investigation. This paper presents a numerical parametric study of blast-induced damage in rock. By varying the strength and stiffness of the blast-induced damaged zone and other relevant parameters, the near-field rock mass response was evaluated in terms of the effects on induced boundary stresses and ground deformation. The continuum method of numerical analysis was used. The input parameters, particularly those relating to strength and stiffness, were estimated using a systematic approach related to the fact that, at shallow depths, the stress and geologic conditions may be highly anisotropic. Due to the lack of data on the post-failure characteristics of the rock mass, the traditional Mohr-Coulomb yield criterion was assumed and used. The results clearly indicate that, as expected, the presence of the blast-induced damage zone does affect the behaviour of the boundary stresses and ground deformation. Potential failure types occurring around the tunnel boundary and their mechanisms have also been identified.

Involvement of DNA polymerase beta in repairing oxidative damages induced by antitumor drug adriamycin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu Shukun; Wu Mei; Zhang Zunzhen, E-mail: zhangzunzhen@163.co

2010-08-01

Adriamycin (ADM) is a widely used antineoplastic drug. However, the increasing cellular resistance has become a serious limitation to ADM clinical application. The most important mechanism related to ADM-induced cell death is oxidative DNA damage mediated by reactive oxygen species (ROS). Base excision repair (BER) is a major pathway in the repair of DNA single strand break (SSB) and oxidized base. In this study, we firstly applied the murine embryo fibroblasts wild-type (pol {beta} +/+) and homozygous pol {beta} null cell (pol {beta} -/-) as a model to investigate ADM DNA-damaging effects and the molecular basis underlying these effects. Here,more » cellular sensitivity to ADM was examined using colorimetric assay and colony forming assay. ADM-induced cellular ROS level and the alteration of superoxide dismutase (SOD) activity were measured by commercial kits. Further, DNA strand break, chromosomal damage and gene mutation were assessed by comet assay, micronucleus test and hprt gene mutation assay, respectively. The results showed that pol {beta} -/- cells were more sensitive to ADM compared with pol {beta} +/+ cells and more severe SSB and chromosomal damage as well as higher hprt gene mutation frequency were observed in pol {beta} -/- cells. ROS level in pol {beta} -/- cells increased along with decreased activity of SOD. These results demonstrated that pol {beta} deficiency could enable ROS accumulation with SOD activity decrease, further elevate oxidative DNA damage, and subsequently result in SSB, chromosome cleavage as well as gene mutation, which may be partly responsible for the cytotoxicity of ADM and the hypersensitivity of pol {beta} -/- cells to ADM. These findings suggested that pol {beta} is vital for repairing oxidative damage induced by ADM.« less

Ultrasonic Assessment of Impact-Induced Damage and Microcracking in Polymer Matrix Composites

NASA Technical Reports Server (NTRS)

Liaw, Benjamin; Zeichner, Glenn; Liu, Yanxiong; Bowles, Kenneth J. (Technical Monitor)

2000-01-01

The main objective of this NASA FAR project is to conduct ultrasonic assessment of impact-induced damage and microcracking in polymer matrix composites at various temperatures. It is believed that the proposed study of impact damage assessment on polymer matrix composites will benefit several NASA's missions and current interests, such as ballistic impact testing of composite fan containment and high strain rate deformation modeling of polymer matrix composites. Currently, impact-induced delamination and fracture in 6061-T6 aluminum/cast acrylic sandwich plates adhered by epoxy were generated in an instrumented drop-weight impact machine. Although only a small dent was produced on the aluminum side when a hemispherical penetrator tup was dropped onto it from a couple of inches, a large ring of delamination at the interface was observed. The delamination damage was often accompanied by severe shattering in the acrylic substratum. Damage patterns in the acrylic layer include radial and ring cracks and, together with delamination at the interface, may cause peeling-off of acrylic material from the sandwich plate. Theory of stress-wave propagation can be used to explain these damage patterns. The impact tests were conducted at various temperatures. The results also show clearly that temperature effect is very important in impact damage. For pure cast acrylic nil-ductile transition (NDT) occurs between 185-195 F Excessive impact energy was dissipated into fracture energy when tested at temperature below this range or through plastic deformation when tested at temperature above the NDT temperature. Results from this study will be used as baseline data for studying fiber-metal laminates, such as GLARE and ARALL for advanced aeronautical and astronautical applications.

Effects of ozone oxidative preconditioning on radiation-induced organ damage in rats

PubMed Central

Gultekin, Fatma Ayca; Bakkal, Bekir Hakan; Guven, Berrak; Tasdoven, Ilhan; Bektas, Sibel; Can, Murat; Comert, Mustafa

2013-01-01

Because radiation-induced cellular damage is attributed primarily to harmful effects of free radicals, molecules with direct free radical scavenging properties are particularly promising as radioprotectors. It has been demonstrated that controlled ozone administration may promote an adaptation to oxidative stress, preventing the damage induced by reactive oxygen species. Thus, we hypothesized that ozone would ameliorate oxidative damage caused by total body irradiation (TBI) with a single dose of 6 Gy in rat liver and ileum tissues. Rats were randomly divided into groups as follows: control group; saline-treated and irradiated (IR) groups; and ozone oxidative preconditioning (OOP) and IR groups. Animals were exposed to TBI after a 5-day intraperitoneal pretreatment with either saline or ozone (1 mg/kg/day). They were decapitated at either 6 h or 72 h after TBI. Plasma, liver and ileum samples were obtained. Serum AST, ALT and TNF-α levels were elevated in the IR groups compared with the control group and were decreased after treatment with OOP. TBI resulted in a significant increase in the levels of MDA in the liver and ileal tissues and a decrease of SOD activities. The results demonstrated that the levels of MDA liver and ileal tissues in irradiated rats that were pretreated with ozone were significantly decreased, while SOD activities were significantly increased. OOP reversed all histopathological alterations induced by irradiation. In conclusion, data obtained from this study indicated that ozone could increase the endogenous antioxidant defense mechanism in rats and there by protect the animals from radiation-induced organ toxicity. PMID:22915786

Calpain-mediated breakdown of cytoskeletal proteins contributes to cholecystokinin-induced damage of rat pancreatic acini.

PubMed

Weber, Heike; Hühns, Saskia; Lüthen, Frank; Jonas, Ludwig

2009-08-01

The cytosolic cysteine protease calpain is implicated in a multitude of cellular functions but also plays a role in cell damage. Our previous results suggest that an activation of calpain accompanied by a decrease in its endogenous inhibitor calpastatin may contribute to pancreatic damage during cerulein-induced acute pancreatitis. The present study aimed at the time course of secretagogue-induced calpain activation and cellular substrates of the protease. Isolated rat pancreatic acini were incubated with a supramaximal concentration of cholecystokinin (0.1 microM CCK) for 30 min in the presence or absence of the calpain inhibitor Z-Val-Phe methyl ester (100 microM ZVP). The activation of calpain and the expression of calpastatin and the actin cytoskeleton-associated proteins alphaII-spectrin, E-cadherin and vinculin were studied by immunoblotting. The cell damage was assessed by lactate dehydrogenase release and ultrastructural analysis including fluorescence-labelled actin filaments. Immediately after administration, CCK led to activation of both calpain isoforms, mu- and m-calpain. The protease activation was accompanied by a decrease in the E-cadherin level and formation of calpain-specific breakdown products of alphaII-spectrin. A calpain-specific cleavage product of vinculin appeared concomitantly with changes in the actin filament organization. No effect of CCK on calpastatin was found. Inhibition of calpain by ZVP reduced CCK-induced damage of the actin-associated proteins and the cellular ultrastructure including the actin cytoskeleton. The results suggest that CCK-induced acinar cell damage requires activation of calpain and that the actin cytoskeleton belongs to the cellular targets of the protease.

Cardiac c-Kit Biology Revealed by Inducible Transgenesis.

PubMed

Gude, Natalie A; Firouzi, Fareheh; Broughton, Kathleen M; Ilves, Kelli; Nguyen, Kristine P; Payne, Christina R; Sacchi, Veronica; Monsanto, Megan M; Casillas, Alexandria R; Khalafalla, Farid G; Wang, Bingyan J; Ebeid, David E; Alvarez, Roberto; Dembitsky, Walter P; Bailey, Barbara A; van Berlo, Jop; Sussman, Mark A

2018-06-22

Biological significance of c-Kit as a cardiac stem cell marker and role(s) of c-Kit+ cells in myocardial development or response to pathological injury remain unresolved because of varied and discrepant findings. Alternative experimental models are required to contextualize and reconcile discordant published observations of cardiac c-Kit myocardial biology and provide meaningful insights regarding clinical relevance of c-Kit signaling for translational cell therapy. The main objectives of this study are as follows: demonstrating c-Kit myocardial biology through combined studies of both human and murine cardiac cells; advancing understanding of c-Kit myocardial biology through creation and characterization of a novel, inducible transgenic c-Kit reporter mouse model that overcomes limitations inherent to knock-in reporter models; and providing perspective to reconcile disparate viewpoints on c-Kit biology in the myocardium. In vitro studies confirm a critical role for c-Kit signaling in both cardiomyocytes and cardiac stem cells. Activation of c-Kit receptor promotes cell survival and proliferation in stem cells and cardiomyocytes of either human or murine origin. For creation of the mouse model, the cloned mouse c-Kit promoter drives Histone2B-EGFP (enhanced green fluorescent protein; H2BEGFP) expression in a doxycycline-inducible transgenic reporter line. The combination of c-Kit transgenesis coupled to H2BEGFP readout provides sensitive, specific, inducible, and persistent tracking of c-Kit promoter activation. Tagging efficiency for EGFP+/c-Kit+ cells is similar between our transgenic versus a c-Kit knock-in mouse line, but frequency of c-Kit+ cells in cardiac tissue from the knock-in model is 55% lower than that from our transgenic line. The c-Kit transgenic reporter model reveals intimate association of c-Kit expression with adult myocardial biology. Both cardiac stem cells and a subpopulation of cardiomyocytes express c-Kit in uninjured adult heart

Ultrasonic Assessment of Impact-Induced Damage and Microcracking in Polymer Matrix Composites

NASA Technical Reports Server (NTRS)

Gyekanyesi, John (Technical Monitor); Liaw, Benjamin; Villars, Esther; Delmont, Frantz

2003-01-01

The main objective of this NASA Faculty Awards for Research (FAR) project is to conduct ultrasonic assessment of impact-induced damage and microcracking in fiber-metal laminated (FML) composites at various temperatures. It is believed that the proposed study of impact damage assessment on FML composites will benefit several NASA's missions and current interests, such as ballistic impact testing of composite fan containment and high strain rate deformation modeling of polymer matrix composites. Impact-induced damage mechanisms in GLARE and ARALL fiber-metal laminates subject to instrumented drop-weight impacts at various temperatures were studied. GLARE and ARALL are hybrid composites made of alternating layers of aluminum and glass- (for GLARE) and aramid- (for ARALL) fiber reinforced epoxy. Damage in pure aluminum panels impacted by foreign objects was mainly characterized by large plastic deformation surrounding a deep penetration dent. On the other hand, plastic deformation in fiber-metal laminates was often not as severe although the penetration dent was still produced. The more stiff fiber-reinforced epoxy layers provided better bending rigidity; thus, enhancing impact damage tolerance. Severe cracking, however, occurred due to the use of these more brittle fiber-reinforced epoxy layers. Fracture patterns, e.g., crack length and delamination size, were greatly affected by the lay-up configuration rather than by the number of layers, which implies that thickness effect was not significant for the panels tested in this study. Immersion ultrasound techniques were then used to assess damages generated by instrumented drop-weight impacts onto these fiber-metal laminate panels as well as 2024-T3 aluminum/cast acrylic sandwich plates adhered by epoxy. Depending on several parameters, such as impact velocity, mass, temperature, laminate configuration, sandwich construction, etc., various types of impact damage were observed, including plastic deformation, radiating

Quantitative Profiling of DNA Damage and Apoptotic Pathways in UV Damaged Cells Using PTMScan Direct

PubMed Central

Stokes, Matthew P.; Silva, Jeffrey C.; Jia, Xiaoying; Lee, Kimberly A.; Polakiewicz, Roberto D.; Comb, Michael J.

2013-01-01

Traditional methods for analysis of peptides using liquid chromatography and tandem mass spectrometry (LC-MS/MS) lack the specificity to comprehensively monitor specific biological processes due to the inherent duty cycle limitations of the MS instrument and the stochastic nature of the analytical platform. PTMScan Direct is a novel, antibody-based method that allows quantitative LC-MS/MS profiling of specific peptides from proteins that reside in the same signaling pathway. New PTMScan Direct reagents have been produced that target peptides from proteins involved in DNA Damage/Cell Cycle and Apoptosis/Autophagy pathways. Together, the reagents provide access to 438 sites on 237 proteins in these signaling cascades. These reagents have been used to profile the response to UV damage of DNA in human cell lines. UV damage was shown to activate canonical DNA damage response pathways through ATM/ATR-dependent signaling, stress response pathways and induce the initiation of apoptosis, as assessed by an increase in the abundance of peptides corresponding to cleaved, activated caspases. These data demonstrate the utility of PTMScan Direct as a multiplexed assay for profiling specific cellular responses to various stimuli, such as UV damage of DNA. PMID:23344034

Reduction of hydrogen peroxide-induced erythrocyte damage by Carica papaya leaf extract

PubMed Central

Okoko, Tebekeme; Ere, Diepreye

2012-01-01

Objective To investigate the in vitro antioxidant potential of Carica papaya (C. papaya) leaf extract and its effect on hydrogen peroxide-induced erythrocyte damage assessed by haemolysis and lipid peroxidation. Methods Hydroxyl radical scavenging activities, hydrogen ion scavenging activity, metal chelating activity, and the ferrous ion reducing ability were assessed as antioxidant indices. In the other experiment, human erythrocytes were treated with hydrogen peroxide to induce erythrocyte damage. The extract (at various concentrations) was subsequently incubated with the erythrocytes and later analysed for haemolysis and lipid peroxidation as indices for erythrocyte damage. Results Preliminary investigation of the extract showed that the leaf possessed significant antioxidant and free radical scavenging abilities using in vitro models in a concentration dependent manner (P<0.05). The extract also reduced hydrogen peroxide induced erythrocyte haemolysis and lipid peroxidation significantly when compared with ascorbic acid (P<0.05). The IC50 values were 7.33 mg/mL and 1.58 mg/mL for inhibition of haemolysis and lipid peroxidation, respectively. In all cases, ascorbic acid (the reference antioxidant) possessed higher activity than the extract. Conclusions The findings show that C. papaya leaves possess significant bioactive potential which is attributed to the phytochemicals which act in synergy. Thus, the leaves can be exploited for pharmaceutical and nutritional purposes. PMID:23569948

Bamboo salt attenuates CCl4-induced hepatic damage in Sprague-Dawley rats

PubMed Central

Zhao, Xin; Song, Jia-Le; Kil, Jeung-Ha

2013-01-01

Bamboo salt, a Korean folk medicine, is prepared with solar salt (sea salt) and baked several times at high temperatures in a bamboo case. In this study, we compared the preventive effects of bamboo salt and purified and solar salts on hepatic damage induced by carbon tetrachloride in Sprague-Dawley rats. Compared with purified and solar salts, bamboo salts prevented hepatic damage in rats, as evidenced by significantly reduced serum levels of aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase (P < 0.05). Bamboo salt (baked 9×) triggered the greatest reduction in these enzyme levels. In addition, it also reduced the levels of the proinflammatory cytokines interleukin (IL)-6, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α. Histopathological sections of liver tissue demonstrated the protective effect of bamboo salt, whereas sections from animals treated with the other salt groups showed a greater degree of necrosis. We also performed reverse transcription-polymerase chain reaction and western blot analyses of the inflammation-related genes iNOS, COX-2, TNF-α, and IL-1β in rat liver tissues. Bamboo salt induced a significant decrease (~80%) in mRNA and protein expression levels of COX-2, iNOS, TNF-α, and IL-1β, compared with the other salts. Thus, we found that baked bamboo salt preparations could prevent CCl4-induced hepatic damage in vivo. PMID:23964314

Targeting neddylation induces DNA damage and checkpoint activation and sensitizes chronic lymphocytic leukemia B cells to alkylating agents.

PubMed

Paiva, C; Godbersen, J C; Berger, A; Brown, J R; Danilov, A V

2015-07-09

Microenvironment-mediated upregulation of the B-cell receptor (BCR) and nuclear factor-κB (NF-κB) signaling in CLL cells resident in the lymph node and bone marrow promotes apoptosis evasion and clonal expansion. We recently reported that MLN4924 (pevonedistat), an investigational agent that inhibits the NEDD8-activating enzyme (NAE), abrogates stromal-mediated NF-κB pathway activity and CLL cell survival. However, the NAE pathway also assists degradation of multiple other substrates. MLN4924 has been shown to induce DNA damage and cell cycle arrest, but the importance of this mechanism in primary neoplastic B cells has not been studied. Here we mimicked the lymph node microenvironment using CD40 ligand (CD40L)-expressing stroma and interleukin-21 (IL-21) to find that inducing proliferation of the primary CLL cells conferred enhanced sensitivity to NAE inhibition. Treatment of the CD40-stimulated CLL cells with MLN4924 resulted in deregulation of Cdt1, a DNA replication licensing factor, and cell cycle inhibitors p21 and p27. This led to DNA damage, checkpoint activation and G2 arrest. Alkylating agents bendamustine and chlorambucil enhanced MLN4924-mediated DNA damage and apoptosis. These events were more prominent in cells stimulated with IL-21 compared with CD40L alone, indicating that, following NAE inhibition, the culture conditions were able to direct CLL cell fate from an NF-κB inhibition to a Cdt1 induction program. Our data provide insight into the biological consequences of targeting NAE in CLL and serves as further rationale for studying the clinical activity of MLN4924 in CLL, particularly in combination with alkylating agents.

Targeting neddylation induces DNA damage and checkpoint activation and sensitizes chronic lymphocytic leukemia B cells to alkylating agents

PubMed Central

Paiva, C; Godbersen, J C; Berger, A; Brown, J R; Danilov, A V

2015-01-01

Microenvironment-mediated upregulation of the B-cell receptor (BCR) and nuclear factor-κB (NF-κB) signaling in CLL cells resident in the lymph node and bone marrow promotes apoptosis evasion and clonal expansion. We recently reported that MLN4924 (pevonedistat), an investigational agent that inhibits the NEDD8-activating enzyme (NAE), abrogates stromal-mediated NF-κB pathway activity and CLL cell survival. However, the NAE pathway also assists degradation of multiple other substrates. MLN4924 has been shown to induce DNA damage and cell cycle arrest, but the importance of this mechanism in primary neoplastic B cells has not been studied. Here we mimicked the lymph node microenvironment using CD40 ligand (CD40L)-expressing stroma and interleukin-21 (IL-21) to find that inducing proliferation of the primary CLL cells conferred enhanced sensitivity to NAE inhibition. Treatment of the CD40-stimulated CLL cells with MLN4924 resulted in deregulation of Cdt1, a DNA replication licensing factor, and cell cycle inhibitors p21 and p27. This led to DNA damage, checkpoint activation and G2 arrest. Alkylating agents bendamustine and chlorambucil enhanced MLN4924-mediated DNA damage and apoptosis. These events were more prominent in cells stimulated with IL-21 compared with CD40L alone, indicating that, following NAE inhibition, the culture conditions were able to direct CLL cell fate from an NF-κB inhibition to a Cdt1 induction program. Our data provide insight into the biological consequences of targeting NAE in CLL and serves as further rationale for studying the clinical activity of MLN4924 in CLL, particularly in combination with alkylating agents. PMID:26158513

Effects of wet etch processing on laser-induced damage of fused silica surfaces

DOE Office of Scientific and Technical Information (OSTI.GOV)

Battersby, C.L.; Kozlowski, M.R.; Sheehan, L.M.

1998-12-22

Laser-induced damage of transparent fused silica optical components by 355 nm illumination occurs primarily at surface defects produced during the grinding and polishing processes. These defects can either be surface defects or sub-surface damage.Wet etch processing in a buffered hydrogen fluoride (HF) solution has been examined as a tool for characterizing such defects. A study was conducted to understand the effects of etch depth on the damage threshold of fused silica substrates. The study used a 355 nm, 7.5 ns, 10 Hz Nd:YAG laser to damage test fused silica optics through various wet etch processing steps. Inspection of the surfacemore » quality was performed with Nomarski microscopy and Total Internal Reflection Microscopy. The damage test data and inspection results were correlated with polishing process specifics. The results show that a wet etch exposes subsurface damage while maintaining or improving the laser damage performance. The benefits of a wet etch must be evaluated for each polishing process.« less

Paraquat-induced ultrastructural changes and DNA damage in the nervous system is mediated via oxidative-stress-induced cytotoxicity in Drosophila melanogaster.

PubMed

Mehdi, Syed Hassan; Qamar, Ayesha

2013-08-01

Paraquat (PQ), a quaternary nitrogen herbicide, is commonly used as a pesticide despite of its high toxicity. Our study evaluated the effect of subchronic PQ exposure on the neuropathology, genotoxicity, and antioxidant activity on the nervous tissue of Drosophila melanogaster. We also explored the behavioral effect of PQ on D. melanogaster. Furthermore, we attempted to validate the mechanism by evaluating PQ-induced cytotoxicity on the D-Mel2 cell lines. The fruit fly D. melanogaster serves as a feasible model to understand the mechanism of neurodegenerative diseases. Our study shows a dose-dependent PQ-induced neuropathology in the brain tissue of D. melanogaster as evidenced by hematoxylin and eosin staining, silver nitrate staining, and transmission electron microscopy. Electron microscopic study of D. melanogaster brain tissue exhibited vacuolar degeneration and significant neuronal damage across the nervous tissue structure in comparison with control. Our findings also indicate a dose-dependent locomotor impairment and decreased superoxide dismutase (SOD) specific activity in PQ-treated D. melanogaster. These PQ-induced neuroanatomical changes and decreased SOD specific activity showed a significant association with oxidative DNA damage as observed by alkaline comet assay. Additionally, we show, for the first time, a dose-dependent PQ-induced cytotoxicity in the D-Mel2 cells suggesting loss of neuronal cell viability via cytotoxic damage. Our data suggest that PQ exposure results in neurodegeneration in D. melanogaster and that fruit fly is a suitable in vivo model for correlating the neuroanatomical changes with neurotoxic damages to nervous system.

Oleuropein Prevents Azoxymethane-Induced Colon Crypt Dysplasia and Leukocytes DNA Damage in A/J Mice.

PubMed

Sepporta, Maria Vittoria; Fuccelli, Raffaela; Rosignoli, Patrizia; Ricci, Giovanni; Servili, Maurizio; Fabiani, Roberto

2016-08-19

Previous studies have shown that the precursor of olive oil secoiridoids, Oleuropein (OL) has several in vitro chemopreventive properties. OL inhibits proliferation and induces apoptosis in breast, thyroid, prostate, and colorectal cancer (CRC) cells. Much less is known about the effects of OL on animal models of carcinogenesis. In this study, we investigated the ability of OL to prevent the azoxymethane (AOM)-induced colon cancer upset and DNA damage in mice. Animals, fed with a basal diet either enriched or not with OL (125 mg/kg), were injected with AOM (10 mg/kg, once a week for 6 weeks) and sacrificed after either 7 weeks for histological analysis of colon crypt dysplasia and evaluation of DNA damage in leukocytes or 17 weeks for counting the macroscopically observable colon tumors. An OL-enriched diet prevented the AOM-induced preneoplastic lesions in different colon segments, reducing the severity of crypt dysplasia and DNA damage in peripheral leukocytes. In addition, OL significantly reduced the AOM-induced tumor incidence from 57% to 14% (P < .05, chi-square test) in the medial colon segment. This study shows that OL is able to prevent CRC and DNA damage in mice treated with the carcinogen AOM. These results stimulate further human cancer prevention studies with OL-enriched food supplements that are actually available on the market.

Angiotensin-(1-7) protects from brain damage induced by shiga toxin 2-producing enterohemorrhagic Escherichia coli.

PubMed

Goldstein, Jorge; Carden, Tomás R; Perez, María J; Taira, Carlos A; Höcht, Christian; Gironacci, Mariela M

2016-12-01

Shiga toxin 2 (Stx2)-producing enterohemorrhagic induced brain damage. Since a cerebroprotective action was reported for angiotensin (Ang)-(1-7), our aim was to investigate whether Ang-(1-7) protects from brain damage induced by Stx2-producing enterohemorrhagic Escherichia coli The anterior hypothalamic area of adult male Wistar rats was injected with saline solution or Stx2 or Stx2 plus Ang-(1-7) or Stx2 plus Ang-(1-7) plus A779. Rats received a single injection of Stx2 at the beginning of the experiment, and Ang-(1-7), A779, or saline was administered daily in a single injection for 8 days. Cellular ultrastructural changes were analyzed by transmission electron microscopy. Stx2 induced neurodegeneration, axonal demyelination, alterations in synapse, and oligodendrocyte and astrocyte damage, accompanied by edema. Ang-(1-7) prevented neuronal damage triggered by the toxin in 55.6 ± 9.5% of the neurons and the Stx2-induced synapse dysfunction was reversed. In addition, Ang-(1-7) blocked Stx2-induced demyelination in 92 ± 4% of the axons. Oligodendrocyte damage caused by Stx2 was prevented by Ang-(1-7) but astrocytes were only partially protected by the peptide (38 ± 5% of astrocytes were preserved). Ang-(1-7) treatment resulted in 50% reduction in the number of activated microglial cells induced by Stx2, suggesting an anti-inflammatory action. All these beneficial effects elicited by Ang-(1-7) were blocked by the Mas receptor antagonist and thus it was concluded that Ang-(1-7) protects mainly neurons and oligodendrocytes, and partially astrocytes, in the central nervous system through Mas receptor stimulation. Copyright © 2016 the American Physiological Society.

Analysis of nicotine-induced DNA damage in cells of the human respiratory tract.

PubMed

Ginzkey, Christian; Stueber, Thomas; Friehs, Gudrun; Koehler, Christian; Hackenberg, Stephan; Richter, Elmar; Hagen, Rudolf; Kleinsasser, Norbert H

2012-01-05

Epithelium of the upper and lower airways is a common origin of tobacco-related cancer. The main tobacco alkaloid nicotine may be associated with tumor progression. The potential of nicotine in inducing DNA mutations as a step towards cancer initiation is still controversially discussed. Different subtypes of nicotinic acetylcholine receptors (nAChR) are expressed in human nasal mucosa and a human bronchial cell line representing respiratory mucosa as a possible target for receptor-mediated pathways. In the present study, both cell systems were investigated with respect to DNA damage induced by nicotine and its mechanisms. Specimens of human nasal mucosa were harvested during surgery of the nasal air passage. After enzymatic digestion over night, single cells were exposed to an increasing nicotine concentration between 0.001 mM and 4.0mM. In a second step co-incubation was performed using the antioxidant N-acetylcysteine (NAC) and the nAChR antagonist mecamylamine. DNA damage was assessed using the alkali version of the comet assay. Dose finding experiments for mecamylamine to evaluate the maximal inhibitory effect were performed in the human bronchial cell line BEAS-2B with an increasing mecamylamine concentration and a constant nicotine concentration. The influence of nicotine in the apoptotic pathway was evaluated in BEAS-2B cells with the TUNEL assay combined with flow cytometry. After 1h of nicotine exposure with 0.001, 0.01, 0.1, 1.0 and 4.0mM, significant DNA damage was determined at 1.0mM. Further co-incubation experiments with mecamylamine and NAC were performed using 1.0mM of nicotine. The strongest inhibitory effect was measured at 1.0mM mecamylamine and this concentration was used for co-incubation. Both, the antioxidant NAC at a concentration of 1.0mM, based on the literature, as well as the receptor antagonist were capable of complete inhibition of the nicotine-induced DNA migration in the comet assay. A nicotine-induced increase or decrease in

In situ TEM observation of alpha-particle induced annealing of radiation damage in Durango apatite.

PubMed

Li, Weixing; Shen, Yahui; Zhou, Yueqing; Nan, Shuai; Chen, Chien-Hung; Ewing, Rodney C

2017-10-26

A major issue in thermochronology and U-Th-Pb dating is the effect of radiation damage, created by α-recoils from α-decay events, on the diffusion of radiogenic elements (e.g., He and Pb) in host mineral. Up until now, thermal events have been considered as the only source of energy for the recovery of radiation-damage. However, irradiation, such as from the α-particle of the α-decay event, can itself induce damage recovery. Quantification of radiation-induced recovery caused by α-particles during α-decay events has not been possible, as the recovery process at the atomic-scale has been difficult to observe. Here we present details of the dynamics of the amorphous-to-crystalline transition process during α-particle irradiations using in situ transmission electron microscopy (TEM) and consecutive ion-irradiations: 1 MeV Kr 2+ (simulating α-recoil damage), followed by 400 keV He + (simulating α-particle annealing). Upon the He + irradiation, partial recrystallization of the original, fully-amorphous Durango apatite was clearly evident and quantified based on the gradual appearance of new crystalline domains in TEM images and new diffraction maxima in selected area electron diffraction patterns. Thus, α-particle induced annealing occurs and must be considered in models of α-decay event damage and its effect on the diffusion of radiogenic elements in geochronology and thermochronology.

Effects of a Strength Training Session After an Exercise Inducing Muscle Damage on Recovery Kinetics.

PubMed

Abaïdia, Abd-Elbasset; Delecroix, Barthélémy; Leduc, Cédric; Lamblin, Julien; McCall, Alan; Baquet, Georges; Dupont, Grégory

2017-01-01

Abaïdia, A-E, Delecroix, B, Leduc, C, Lamblin, J, McCall, A, Baquet, G, and Dupont, G. Effects of a strength training session after an exercise inducing muscle damage on recovery kinetics. J Strength Cond Res 31(1): 115-125, 2017-The purpose of this study was to investigate the effects of an upper-limb strength training session the day after an exercise inducing muscle damage on recovery of performance. In a randomized crossover design, subjects performed the day after the exercise, on 2 separate occasions (passive vs. active recovery conditions) a single-leg exercise (dominant in one condition and nondominant in the other condition) consisting of 5 sets of 15 eccentric contractions of the knee flexors. Active recovery consisted of performing an upper-body strength training session the day after the exercise. Creatine kinase, hamstring strength, and muscle soreness were assessed immediately and 20, 24, and 48 hours after exercise-induced muscle damage. The upper-body strength session, after muscle-damaging exercise accelerated the recovery of slow concentric force (effect size = 0.65; 90% confidence interval = -0.06 to 1.32), but did not affect the recovery kinetics for the other outcomes. The addition of an upper-body strength training session the day after muscle-damaging activity does not negatively affect the recovery kinetics. Upper-body strength training may be programmed the day after a competition.

Dietary spices protect against hydrogen peroxide-induced DNA damage and inhibit nicotine-induced cancer cell migration.

PubMed

Jayakumar, R; Kanthimathi, M S

2012-10-01

Spices are rich sources of antioxidants due to the presence of phenols and flavonoids. In this study, the DNA protecting activity and inhibition of nicotine-induced cancer cell migration of 9 spices were analysed. Murine fibroblasts (3T3-L1) and human breast cancer (MCF-7) cells were pre-treated with spice extracts and then exposed to H₂O₂ and nicotine. The comet assay was used to analyse the DNA damage. Among the 9 spices, ginger, at 50 μg/ml protected against 68% of DNA damage in 3T3-L1 cells. Caraway, cumin and fennel showed statistically significant (p<0.05) DNA protecting activity. Treatment of MCF-7 cells with nicotine induced cell migration, whereas pre-treatment with spices reduced this migration. Pepper, long pepper and ginger exhibited a high rate of inhibition of cell migration. The results of this study prove that spices protect DNA and inhibit cancer cell migration. Copyright © 2012 Elsevier Ltd. All rights reserved.

Antioxidant Protective Effect of Honey in Cigarette Smoke-Induced Testicular Damage in Rats

PubMed Central

Mohamed, Mahaneem; Sulaiman, Siti Amrah; Jaafar, Hasnan; Sirajudeen, Kuttulebbai Nainamohamed Salam

2011-01-01

Cigarette smoke (CS) can cause testicular damage and we investigated the possible protective effect of honey against CS-induced testicular damage and oxidative stress in rats. CS exposure (8 min, 3 times daily) and honey supplementation (1.2 g/kg daily) were given for 13 weeks. Rats exposed to CS significantly had smaller seminiferous tubules diameter and epithelial height, lower Leydig cell count and increased percentage of tubules with germ cell loss. CS also produced increased lipid peroxidation (TBARS) and glutathione peroxidase (GPx) activity, as well as reduced total antioxidant status (TAS) and activities of superoxide dismutase (SOD) and catalase (CAT). However, supplementation of honey significantly reduced histological changes and TBARS level, increased TAS level, as well as significantly restored activities of GPx, SOD and CAT in rat testis. These findings may suggest that honey has a protective effect against damage and oxidative stress induced by CS in rat testis. PMID:22016605

Gc-protein-derived macrophage activating factor counteracts the neuronal damage induced by oxaliplatin.

PubMed

Morucci, Gabriele; Branca, Jacopo J V; Gulisano, Massimo; Ruggiero, Marco; Paternostro, Ferdinando; Pacini, Alessandra; Di Cesare Mannelli, Lorenzo; Pacini, Stefania

2015-02-01

Oxaliplatin-based regimens are effective in metastasized advanced cancers. However, a major limitation to their widespread use is represented by neurotoxicity that leads to peripheral neuropathy. In this study we evaluated the roles of a proven immunotherapeutic agent [Gc-protein-derived macrophage activating factor (GcMAF)] in preventing or decreasing oxaliplatin-induced neuronal damage and in modulating microglia activation following oxaliplatin-induced damage. The effects of oxaliplatin and of a commercially available formula of GcMAF [oleic acid-GcMAF (OA-GcMAF)] were studied in human neurons (SH-SY5Y cells) and in human microglial cells (C13NJ). Cell density, morphology and viability, as well as production of cAMP and expression of vascular endothelial growth factor (VEGF), markers of neuron regeneration [neuromodulin or growth associated protein-43 (Gap-43)] and markers of microglia activation [ionized calcium binding adaptor molecule 1 (Iba1) and B7-2], were determined. OA-GcMAF reverted the damage inflicted by oxaliplatin on human neurons and preserved their viability. The neuroprotective effect was accompanied by increased intracellular cAMP production, as well as by increased expression of VEGF and neuromodulin. OA-GcMAF did not revert the effects of oxaliplatin on microglial cell viability. However, it increased microglial activation following oxaliplatin-induced damage, resulting in an increased expression of the markers Iba1 and B7-2 without any concomitant increase in cell number. When neurons and microglial cells were co-cultured, the presence of OA-GcMAF significantly counteracted the toxic effects of oxaliplatin. Our results demonstrate that OA-GcMAF, already used in the immunotherapy of advanced cancers, may significantly contribute to neutralizing the neurotoxicity induced by oxaliplatin, at the same time possibly concurring to an integrated anticancer effect. The association between these two powerful anticancer molecules would probably produce

A spatial-dynamic value transfer model of economic losses from a biological invasion

Treesearch

Thomas P. Holmes; Andrew M. Liebhold; Kent F. Kovacs; Betsy Von Holle

2010-01-01

Rigorous assessments of the economic impacts of introduced species at broad spatial scales are required to provide credible information to policy makers. We propose that economic models of aggregate damages induced by biological invasions need to link microeconomic analyses of site-specific economic damages with spatial-dynamic models of value change associated with...

Nrf2 deficiency potentiates methamphetamine-induced dopaminergic axonal damage and gliosis in the striatum.

PubMed

Granado, Noelia; Lastres-Becker, Isabel; Ares-Santos, Sara; Oliva, Idaira; Martin, Eduardo; Cuadrado, Antonio; Moratalla, Rosario

2011-12-01

Oxidative stress that correlates with damage to nigrostriatal dopaminergic neurons and reactive gliosis in the basal ganglia is a hallmark of methamphetamine (METH) toxicity. In this study, we analyzed the protective role of the transcription factor Nrf2 (nuclear factor-erythroid 2-related factor 2), a master regulator of redox homeostasis, in METH-induced neurotoxicity. We found that Nrf2 deficiency exacerbated METH-induced damage to dopamine neurons, shown by an increase in loss of tyrosine hydroxylase (TH)- and dopamine transporter (DAT)-containing fibers in striatum. Consistent with these effects, Nrf2 deficiency potentiated glial activation, indicated by increased striatal expression of markers for microglia (Mac-1 and Iba-1) and astroglia (GFAP) one day after METH administration. At the same time, Nrf2 inactivation dramatically potentiated the increase in TNFα mRNA and IL-15 protein expression in GFAP+ cells in the striatum. In sharp contrast to the potentiation of striatal damage, Nrf2 deficiency did not affect METH-induced dopaminergic neuron death or expression of glial markers or proinflammatory molecules in the substantia nigra. This study uncovers a new role for Nrf2 in protection against METH-induced inflammatory and oxidative stress and striatal degeneration. Copyright © 2011 Wiley‐Liss, Inc.

The role of defects in laser-induced modifications of silica coatings and fused silica using picosecond pulses at 1053 nm: I Damage morphology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Laurence, T. A.; Ly, S.; Shen, N.

Laser-induced damage with ps pulse widths straddles the transition from intrinsic, multi-photon ionization and avalanche ionization-based ablation with fs pulses to defect-dominated, thermal-based damage with ns pulses. We investigated the morphology of damage for fused silica and silica coatings between 1 ps and 60 ps at 1053 nm. Using calibrated laser-induced damage experiments, in situ imaging, and high-resolution optical microscopy, atomic force microscopy, and scanning electron microscopy, we show that defects play an important role in laser-induced damage down to 1 ps. Three types of damage are observed: ablation craters, ultra-high density pits, and smooth, circular depressions with central pits.more » For 10 ps and longer, the smooth, circular depressions limit the damage performance of fused silica and silica coatings. The observed high-density pits and material removal down to 3 ps indicate that variations in surface properties limit the laser-induced damage onset to a greater extent than expected below 60 ps. Below 3 ps, damage craters are smoother although there is still evidence as seen by AFM of inhomogeneous laser-induced damage response very near the damage onset. These results show that modeling the damage onset only as a function of pulse width does not capture the convoluted processes leading to laser induced damage with ps pulses. It is necessary to account for the effects of defects on the processes leading to laser-induced damage. In conclusion, the effects of isolated defects or inhomogeneities are most pronounced above 3 ps but are still discernible and possibly important down to the shortest pulse width investigated here.« less

The role of defects in laser-induced modifications of silica coatings and fused silica using picosecond pulses at 1053 nm: I Damage morphology

DOE PAGES

Laurence, T. A.; Ly, S.; Shen, N.; ...

2017-06-22

Laser-induced damage with ps pulse widths straddles the transition from intrinsic, multi-photon ionization and avalanche ionization-based ablation with fs pulses to defect-dominated, thermal-based damage with ns pulses. We investigated the morphology of damage for fused silica and silica coatings between 1 ps and 60 ps at 1053 nm. Using calibrated laser-induced damage experiments, in situ imaging, and high-resolution optical microscopy, atomic force microscopy, and scanning electron microscopy, we show that defects play an important role in laser-induced damage down to 1 ps. Three types of damage are observed: ablation craters, ultra-high density pits, and smooth, circular depressions with central pits.more » For 10 ps and longer, the smooth, circular depressions limit the damage performance of fused silica and silica coatings. The observed high-density pits and material removal down to 3 ps indicate that variations in surface properties limit the laser-induced damage onset to a greater extent than expected below 60 ps. Below 3 ps, damage craters are smoother although there is still evidence as seen by AFM of inhomogeneous laser-induced damage response very near the damage onset. These results show that modeling the damage onset only as a function of pulse width does not capture the convoluted processes leading to laser induced damage with ps pulses. It is necessary to account for the effects of defects on the processes leading to laser-induced damage. In conclusion, the effects of isolated defects or inhomogeneities are most pronounced above 3 ps but are still discernible and possibly important down to the shortest pulse width investigated here.« less

Estrogens and progression of diabetic kidney damage.

PubMed

Doublier, Sophie; Lupia, Enrico; Catanuto, Paola; Elliot, Sharon J

2011-01-01

It is generally accepted that estrogens affect and modulate the development and progression of chronic kidney diseases (CKD) not related to diabetes. Clinical studies have indeed demonstrated that the severity and rate of progression of renal damage tends to be greater among men, compared with women. Experimental studies also support the notion that female sex is protective and male sex permissive, for the development of CKD in non-diabetics, through the opposing actions of estrogens and testosterone. However, when we consider diabetes-induced kidney damage, in the setting of either type 1 or type 2 diabetes, the contribution of gender to the progression of renal disease is somewhat uncertain. Previous studies on the effects of estrogens in the pathogenesis of progressive kidney damage have primarily focused on mesangial cells. More recently, data on the effects of estrogens on podocytes, the cell type whose role may include initiation of progressive diabetic renal disease, became available. The aim of this review will be to summarize the main clinical and experimental data on the effects of estrogens on the progression of diabetes-induced kidney injury. In particular, we will highlight the possible biological effects of estrogens on podocytes, especially considering those critical for the pathogenesis of diabetic kidney damage.

The Extract of D. dasycarpus Ameliorates Oxazolone-Induced Skin Damage in Mice by Anti-Inflammatory and Antioxidant Mechanisms.

PubMed

Chang, Tsong-Min; Yang, Ting-Ya; Niu, Yu-Lin; Huang, Huey-Chun

2018-06-15

Dictamni dasycarpus is a type of Chinese medicine made from the root bark of D. dasycarpus . It has been reported to show a wide spectrum of biological and pharmacological effects, for example, it has been used widely for the treatment of rheumatism, nettle rash, itching, jaundice, chronic hepatitis and skin diseases. In the current study, D. dasycarpus extract was investigated for its antioxidant and anti-inflammatory effects, as well as its capability to alleviate oxazolone-induced skin damage in mice. The possible anti-inflammatory mechanism of D. dasycarpus extract against oxidative challenge was elucidated by measuring the levels of reactive oxygen species (ROS) production, interleukin-6, Tumor necrosis factor-α, NLRP3 (NACHT, LRR and PYD domains-containing protein 3 (NALP3)) inflammasome and interleukin-1β in HaCaT cells. D. dasycarpus extract did not affect cell viability in basal conditions. The extract significantly reduced oxazolone-induced epidermal swelling compared to untreated animal in the hairless albino mice (ICR mice) model. At the molecular level, Western blot assays indicated that the D. dasycarpus extract attenuated oxazolone-induced activation of apoptosis-associated speck-like protein containing CARD (ASC), procaspase-1, NF-κB and mitogen-activated protein kinase (MAPKs) such as c-Jun N-terminal protein kinase (JNK) and p38. This study demonstrates that D. dasycarpus extract could protect skin cells against oxidative and inflammatory insult by modulating the intracellular levels of ROS, TNF-α, interleukin-1, interleukin-6, NLR family pyrin domain containing 3 (NLRP3) inflammasome generation, antioxidant enzyme activity and cell signaling pathways. D. dasycarpus extract also attenuated the expression of NF-κB in HaCaT keratinocytes and thereby effectively downregulated inflammatory responses in the skin. Furthermore, D. dasycarpus extract alleviated oxazolone-induced damage in mice. Our results suggest the

Alpha-phellandrene-induced DNA damage and affect DNA repair protein expression in WEHI-3 murine leukemia cells in vitro.

PubMed

Lin, Jen-Jyh; Wu, Chih-Chung; Hsu, Shu-Chun; Weng, Shu-Wen; Ma, Yi-Shih; Huang, Yi-Ping; Lin, Jaung-Geng; Chung, Jing-Gung

2015-11-01

Although there are few reports regarding α-phellandrene (α-PA), a natural compound from Schinus molle L. essential oil, there is no report to show that α-PA induced DNA damage and affected DNA repair associated protein expression. Herein, we investigated the effects of α-PA on DNA damage and repair associated protein expression in murine leukemia cells. Flow cytometric assay was used to measure the effects of α-PA on total cell viability and the results indicated that α-PA induced cell death. Comet assay and 4,6-diamidino-2-phenylindole dihydrochloride staining were used for measuring DNA damage and condensation, respectively, and the results indicated that α-PA induced DNA damage and condensation in a concentration-dependent manner. DNA gel electrophoresis was used to examine the DNA damage and the results showed that α-PA induced DNA damage in WEHI-3 cells. Western blotting assay was used to measure the changes of DNA damage and repair associated protein expression and the results indicated that α-PA increased p-p53, p-H2A.X, 14-3-3-σ, and MDC1 protein expression but inhibited the protein of p53, MGMT, DNA-PK, and BRCA-1. © 2014 Wiley Periodicals, Inc.

KM-34, a Novel Antioxidant Compound, Protects against 6-Hydroxydopamine-Induced Mitochondrial Damage and Neurotoxicity.

PubMed

Fonseca-Fonseca, Luis Arturo; Nuñez-Figueredo, Yanier; Sánchez, Jeney Ramírez; Guerra, Maylin Wong; Ochoa-Rodríguez, Estael; Verdecia-Reyes, Yamila; Hernádez, René Delgado; Menezes-Filho, Noelio J; Costa, Teresa Cristina Silva; de Santana, Wagno Alcântara; Oliveira, Joana L; Segura-Aguilar, Juan; da Silva, Victor Diogenes Amaral; Costa, Silva Lima

2018-01-02

The etiology of Parkinson's disease is not completely understood and is believed to be multifactorial. Neuronal disorders associated to oxidative stress and mitochondrial dysfunction are widely considered major consequences. The aim of this study was to investigate the effect of the synthetic arylidenmalonate derivative 5-(3,4-dihydroxybenzylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione (KM-34), in oxidative stress and mitochondrial dysfunction induced by 6-hydroxydopamine (6-OHDA). Pretreatment (2 h) with KM-34 (1 and 10 μM) markedly attenuated 6-OHDA-induced PC12 cell death in a concentration-dependent manner. KM-34 also inhibited H 2 O 2 generation, mitochondrial swelling, and membrane potential dissipation after 6-OHDA-induced mitochondrial damage. In vivo, KM-34 treatment (1 and 2 mg/Kg) reduced percentage of asymmetry (cylinder test) and increased the vertical exploration (open field) with respect to untreated injured animals; KM-34 also reduced glial fibrillary acidic protein overexpression and increased tyrosine hydroxylase-positive cell number, both in substantia nigra pars compacta. These results demonstrate that KM-34 present biological effects associated to mitoprotection and neuroprotection in vitro, moreover, glial response and neuroprotection in SNpc in vivo. We suggest that KM-34 could be a putative neuroprotective agent for inhibiting the progressive neurodegenerative disease associated to oxidative stress and mitochondrial dysfunction.

Longitudinal diffusion tensor magnetic resonance imaging study of radiation-induced white matter damage in a rat model.

PubMed

Wang, Silun; Wu, Ed X; Qiu, Deqiang; Leung, Lucullus H T; Lau, Ho-Fai; Khong, Pek-Lan

2009-02-01

Radiation-induced white matter (WM) damage is a major side effect of whole brain irradiation among childhood cancer survivors. We evaluate longitudinally the diffusion characteristics of the late radiation-induced WM damage in a rat model after 25 and 30 Gy irradiation to the hemibrain at 8 time points from 2 to 48 weeks postradiation. We hypothesize that diffusion tensor magnetic resonance imaging (DTI) indices including fractional anisotropy (FA), trace, axial diffusivity (lambda(//)), and radial diffusivity (lambda( perpendicular)) can accurately detect and monitor the histopathologic changes of radiation-induced WM damage, measured at the EC, and that these changes are dose and time dependent. Results showed a progressive reduction of FA, which was driven by reduction in lambda(//) from 4 to 40 weeks postradiation, and an increase in lambda( perpendicular) with return to baseline in lambda(//) at 48 weeks postradiation. Histologic evaluation of irradiated WM showed reactive astrogliosis from 4 weeks postradiation with reversal at 36 weeks, and demyelination, axonal degeneration, and necrosis at 48 weeks postradiation. Moreover, changes in lambda(//) correlated with reactive astrogliosis (P < 0.01) and lambda( perpendicular) correlated with demyelination (P < 0.01). Higher radiation dose (30 Gy) induced earlier and more severe histologic changes than lower radiation dose (25 Gy), and these differences were reflected by the magnitude of changes in lambda(//) and lambda( perpendicular). DTI indices reflected the histopathologic changes of WM damage and our results support the use of DTI as a biomarker to noninvasively monitor radiation-induced WM damage.

The organophosphate insecticide chlorpyrifos confers its genotoxic effects by inducing DNA damage and cell apoptosis.

PubMed

Li, Diqiu; Huang, Qingchun; Lu, Miaoqing; Zhang, Lei; Yang, Zhichuan; Zong, Mimi; Tao, Liming

2015-09-01

The organophosphate insecticide chlorpyrifos (CPF) is known to induce neurological effects, malformation and micronucleus formation, persistent developmental disorders, and maternal toxicity in rats and mice. The binding of chlorpyrifos with DNA to produce DNA adducts leads to an increasing social concern about the genotoxic risk of CPF in human, but CPF-induced cytotoxicity through DNA damage and cell apoptosis is not well understood. Here, we quantified the cytotoxicity and potential genotoxicity of CPF using the alkaline comet assay, γH2AX foci formation, and the DNA laddering assay in order to detect DNA damage and apoptosis in human HeLa and HEK293 cells in vitro. Drosophila S2 cells were used as a positive control. The alkaline comet assay showed that sublethal concentrations of CPF induced significant concentration-dependent increases in single-strand DNA breaks in the treated cells compared with the control. The percentage of γH2AX-positive HeLa cells revealed that CPF also causes DNA double-strand breaks in a time-dependent manner. Moreover, DNA fragmentation analysis demonstrated that exposure to CPF induced a significant concentration- and time-dependent increase in cell apoptosis. We conclude that CPF is a strongly genotoxic agent that induces DNA damage and cell apoptosis. Copyright © 2015 Elsevier Ltd. All rights reserved.

Laser induced damage thresholds and laser safety levels. Do the units of measurement matter?

NASA Astrophysics Data System (ADS)

Wood, R. M.

1998-04-01

The commonly used units of measurement for laser induced damage are those of peak energy or power density. However, the laser induced damage thresholds, LIDT, of all materials are well known to be absorption, wavelength, spot size and pulse length dependent. As workers using these values become divorced from the theory it becomes increasingly important to use the correct units and to understand the correct scaling factors. This paper summarizes the theory and highlights the danger of using the wrong LIDT units in the context of potentially hazardous materials, laser safety eyewear and laser safety screens.

Is UV-induced DNA damage greater at higher elevation?

PubMed

Wang, Qing-Wei; Hidema, Jun; Hikosaka, Kouki

2014-05-01

• Although ultraviolet radiation (UV) is known to have negative effects on plant growth, there has been no direct evidence that plants growing at higher elevations are more severely affected by ultraviolet-B (UV-B) radiation, which is known to increase with elevation. We examined damage to DNA, a primary target of UV-B, in the widespread species Polygonum sachalinense (Fallopia sachalinensis) and Plantago asiatica at two elevations.• We sampled leaves of both species at 300 and 1700 m above sea level every 2 h for 11 d across the growing season and determined the level of cyclobutane pyrimidine dimer (CPD), a major product of UV damage to DNA.• The CPD level was significantly influenced by the time of day, date, elevation, and their interactions in both species. The CPD level tended to be higher at noon or on sunny days. DNA damage was more severe at 1700 m than at 300 m: on average, 8.7% greater at high elevation in P. asiatica and 7.8% greater in P. sachalinense Stepwise multiple regression analysis indicated that the CPD level was explained mainly by UV-B and had no significant relationship with other environmental factors such as temperature and photosynthetically active radiation.• UV-induced DNA damage in plants is greater at higher elevations. © 2014 Botanical Society of America, Inc.

Classification of climate-change-induced stresses on biological diversity.

PubMed

Geyer, Juliane; Kiefer, Iris; Kreft, Stefan; Chavez, Veronica; Salafsky, Nick; Jeltsch, Florian; Ibisch, Pierre L

2011-08-01

Conservation actions need to account for and be adapted to address changes that will occur under global climate change. The identification of stresses on biological diversity (as defined in the Convention on Biological Diversity) is key in the process of adaptive conservation management. We considered any impact of climate change on biological diversity a stress because such an effect represents a change (negative or positive) in key ecological attributes of an ecosystem or parts of it. We applied a systemic approach and a hierarchical framework in a comprehensive classification of stresses to biological diversity that are caused directly by global climate change. Through analyses of 20 conservation sites in 7 countries and a review of the literature, we identified climate-change-induced stresses. We grouped the identified stresses according to 3 levels of biological diversity: stresses that affect individuals and populations, stresses that affect biological communities, and stresses that affect ecosystem structure and function. For each stress category, we differentiated 3 hierarchical levels of stress: stress class (thematic grouping with the coarsest resolution, 8); general stresses (thematic groups of specific stresses, 21); and specific stresses (most detailed definition of stresses, 90). We also compiled an overview of effects of climate change on ecosystem services using the categories of the Millennium Ecosystem Assessment and 2 additional categories. Our classification may be used to identify key climate-change-related stresses to biological diversity and may assist in the development of appropriate conservation strategies. The classification is in list format, but it accounts for relations among climate-change-induced stresses. © 2011 Society for Conservation Biology.

Oxidative damage and cell-programmed death induced in Zea mays L. by allelochemical stress.

PubMed

Ciniglia, Claudia; Mastrobuoni, Francesco; Scortichini, Marco; Petriccione, Milena

2015-05-01

The allelochemical stress on Zea mays was analyzed by using walnut husk washing waters (WHWW), a by-product of Juglans regia post-harvest process, which possesses strong allelopathic potential and phytotoxic effects. Oxidative damage and cell-programmed death were induced by WHWW in roots of maize seedlings. Treatment induced ROS burst, with excess of H2O2 content. Enzymatic activities of catalase were strongly increased during the first hours of exposure. The excess in malonildialdehyde following exposure to WHWW confirmed that oxidative stress severely damaged maize roots. Membrane alteration caused a decrease in NADPH oxidase activity along with DNA damage as confirmed by DNA laddering. The DNA instability was also assessed through sequence-related amplified polymorphism assay, thus suggesting the danger of walnut processing by-product and focusing the attention on the necessity of an efficient treatment of WHWW.

Hypertonic stress induces rapid and widespread protein damage in C. elegans

PubMed Central

Burkewitz, Kris; Choe, Keith

2011-01-01

Proteostasis is defined as the homeostatic mechanisms that maintain the function of all cytoplasmic proteins. We recently demonstrated that the capacity of the proteostasis network is a critical factor that defines the limits of cellular and organismal survival in hypertonic environments. The current studies were performed to determine the extent of protein damage induced by cellular water loss. Using worm strains expressing fluorescently tagged foreign and endogenous proteins and proteins with temperature-sensitive point mutations, we demonstrate that hypertonic stress causes aggregation and misfolding of diverse proteins in multiple cell types. Protein damage is rapid. Aggregation of a polyglutamine yellow fluorescent protein reporter is observable with <1 h of hypertonic stress, and aggregate volume doubles approximately every 10 min. Aggregate formation is irreversible and occurs after as little as 10 min of exposure to hypertonic conditions. To determine whether endogenous proteins are aggregated by hypertonic stress, we quantified the relative amount of total cellular protein present in detergent-insoluble extracts. Exposure for 4 h to 400 mM or 500 mM NaCl induced a 55–120% increase in endogenous protein aggregation. Inhibition of insulin signaling or acclimation to mild hypertonic stress increased survival under extreme hypertonic conditions and prevented aggregation of endogenous proteins. Our results demonstrate that hypertonic stress causes widespread and dramatic protein damage and that cells have a significant capacity to remodel the network of proteins that function to maintain proteostasis. These findings have important implications for understanding how cells cope with hypertonic stress and other protein-damaging stressors. PMID:21613604

A new thermo-mechanical coupled DEM model with non-spherical grains for thermally induced damage of rocks

NASA Astrophysics Data System (ADS)

Chen, Zhiqiang; Jin, Xu; Wang, Moran

2018-07-01

Thermally induced damage often occurs in rocks in geophysical systems. Discrete element method (DEM) is a useful tool to model this thermo-mechanical coupled process owing to its explicit representation of fracture initiation and propagation. However, the previous DEM models for this are mostly based on spherical discrete elements, which are not able to capture all consequences (e.g. high ratio of compressive to tensile strength) of real rocks (e.g. granite) composed of complex-geometry grains. In order to overcome this intrinsic limitation, we present a new model allowing to mimick thermally induced damage of brittle rock with non-spherical grains. After validations, the new model is used to study thermal gradient cracking with a special emphasis on the effects from rock heterogeneity. The obtained fracture initiation and propagation are consistent with experimental observations, which demonstrates the ability of current model to reproduce the thermally induced damage of rocks. Meanwhile, the results show that rock heterogeneity influences thermal gradient cracking significantly, and more micro cracks uniformly scattering around the borehole are induced in the heterogeneous sample, which is not good for applications such as nuclear waste disposal. The present model provides a promising approach at micro-scale to explore mechanisms of thermally induced damage of rocks in geological engineering.

REC-2006-A Fractionated Extract of Podophyllum hexandrum Protects Cellular DNA from Radiation-Induced Damage by Reducing the Initial Damage and Enhancing Its Repair In Vivo.

PubMed

Chaudhary, Pankaj; Shukla, Sandeep Kumar; Sharma, Rakesh Kumar

2011-01-01

Podophyllum hexandrum, a perennial herb commonly known as the Himalayan May Apple, is well known in Indian and Chinese traditional systems of medicine. P. hexandrum has been widely used for the treatment of venereal warts, skin infections, bacterial and viral infections, and different cancers of the brain, lung and bladder. This study aimed at elucidating the effect of REC-2006, a bioactive fractionated extract from the rhizome of P. hexandrum, on the kinetics of induction and repair of radiation-induced DNA damage in murine thymocytes in vivo. We evaluated its effect on non-specific radiation-induced DNA damage by the alkaline halo assay in terms of relative nuclear spreading factor (RNSF) and gene-specific radiation-induced DNA damage via semi-quantitative polymerase chain reaction. Whole body exposure of animals with gamma rays (10 Gy) caused a significant amount of DNA damage in thymocytes (RNSF values 17.7 ± 0.47, 12.96 ± 1.64 and 3.3 ± 0.014) and a reduction in the amplification of β-globin gene to 0, 28 and 43% at 0, 15 and 60 min, respectively. Administrating REC-2006 at a radioprotective concentration (15 mg kg(-1) body weight) 1 h before irradiation resulted in time-dependent reduction of DNA damage evident as a decrease in RNSF values 6.156 ± 0.576, 1.647 ± 0.534 and 0.496 ± 0.012, and an increase in β-globin gene amplification 36, 95 and 99%, at 0, 15 and 60 min, respectively. REC-2006 scavenged radiation-induced hydroxyl radicals in a dose-dependent manner stabilized DPPH free radicals and also inhibited superoxide anions. Various polyphenols and flavonoides present in REC-2006 might contribute to scavenging of radiation-induced free radicals, thereby preventing DNA damage and stimulating its repair.

Effects of conventional and hydrogen sulfide-releasing non-steroidal anti-inflammatory drugs in rats with stress-induced and epinephrine-induced gastric damage.

PubMed

Fomenko, Iryna; Sklyarov, Alexander; Bondarchuk, Tetyana; Biletska, Lilya; Panasyuk, Natalia; Wallace, John L

2014-12-01

Mechanisms of gastric defence under conditions of combined influence of acute stress and non-steroidal anti-inflammatory drugs (NSAIDs) are still poorly studied. The aim of this study was to explore the effects of different types of NSAIDs (naproxen, celecoxib and ATB-346) in producing experimental gastric lesions (induced by water-restraint stress (WRS) or by epinephrine (EPN) injection) and to determine the role of lipid peroxidation and the nitric oxide (NO) system in the pathogenesis of the damage. Male rats were used (eight per group) in this work. The NSAIDs were all administered at a dose 10 mg kg(-1) 30 min prior to WRS or EPN injection. Administration of naproxen to the control rats caused development of gastric lesions, whereas administration of a hydrogen sulfide (H2S)-releasing NSAID (ATB-346) or a selective cyclooxygenase-2 inhibitor (celecoxib) did not cause gastric damage. In contrast, lipid peroxidation processes were enhanced in all groups as was the activity of NO synthase (NOS). Pretreatment with naproxen in the WRS model caused an increase in severity of damage and a decrease in NOS activity. ATB-346 displayed beneficial effects, manifested by a decrease in the area of gastric damage, but parameters of lipid peroxidation and the NOS system did not differ substantially from those in the group treated with naproxen. Administration of different NSAIDs under conditions of EPN-induced gastric damage resulted in the decrease in NOS activity and lipid peroxidation. None of the tested NSAIDs exacerbated EPN-induced gastric mucosal injury; indeed, they all reduced the extent of damage.

The possible DNA damage induced by environmental organic compounds: The case of Nonylphenol.

PubMed

Noorimotlagh, Zahra; Mirzaee, Seyyed Abbas; Ahmadi, Mehdi; Jaafarzadeh, Neemat; Rahim, Fakher

2018-08-30

Human impact on the environment leads to the release of many pollutants that produce artificial compounds, which can have harmful effects on the body's endocrine system; these are known as endocrine disruptors (EDs). Nonylphenol (NP) is a chemical compound with a nonyl group that is attached to a phenol ring. NP-induced H 2 AX is a sensitive genotoxic biomarker for detecting possible DNA damage; it also causes male infertility and carcinogenesis. We attempt to comprehensively review all the available evidence about the different ways with descriptive mechanisms for explaining the possible DNA damage that is induced by NP. We systematically searched several databases, including PubMed, Scopus, Web of Science, and gray literature, such as Google Scholar by using medical subheading (MeSH) terms and various combinations of selected keywords from January 1970 to August 2017. The initial search identified 62,737 potentially eligible studies; of these studies, 33 were included according to the established inclusion criteria. Thirty-three selected studies, include the topics of animal model (n = 21), cell line (n = 6), human model (n = 4), microorganisms (n = 1), solid DNA (n = 1), infertility (n = 4), apoptosis (n = 6), and carcinogenesis (n = 3). This review highlighted the possible deleterious effects of NP on DNA damage through the ability to produce ROS/RNS. Finally, it is significant to observe caution at this stage with the continued use of environmental pollutants such as NP, which may induce DNA damage and apoptosis. Copyright © 2018 Elsevier Inc. All rights reserved.

Effect of Pelargonium reniforme roots on alcohol-induced liver damage and oxidative stress.

PubMed

Adewusi, Emmanuel Adekanmi; Afolayan, Anthony Jide

2010-09-01

Ethnobotanical surveys conducted on Pelargonium reniforme Curtis (Geraniaceae) have shown that the aqueous root extracts are used to treat alcohol-induced liver damage. We evaluated the antioxidant properties of the extract and its effects on alcohol-induced hepatotoxicity using Wistar rats. Alcohol-induced hepatotoxicity studies were carried out by observing the effect of the aqueous root extract on some liver marker enzymes, bilirubin, and total protein after liver damage. The levels of some phenolic compounds were determined by standard methods. Also, the reducing power of the plant extract and its ability to scavenge 1,1-diphenyl-2-picrylhydrazyl (DPPH*) and 2,2'-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS*+) radicals were determined to evaluate its antioxidant activity. The results obtained show that the plant extract possessed significant antioxidant activity. It had a significant level of phenolic compounds, scavenged DPPH* and ABTS*+ radicals effectively, and demonstrated good reducing power. This may indicate that the plant contained compounds which can remove toxic metabolites following alcohol abuse. Serum analysis of animals treated with only ethanol showed a significant increase in the levels of liver marker enzymes and total and unconjugated bilirubin, while a significant decrease was observed in the levels of conjugated bilirubin and total proteins. Administration of the plant extract restored the levels of these markers to normal levels, and this indicates the ability of the plant extract to restore normal functioning of a damaged liver. The study shows that P. reniforme is a potential source of antioxidants and compounds which are useful in treating alcoholic liver damage.

Protective roles of single-wall carbon nanotubes in ultrasonication-induced DNA base damage.

PubMed

Petersen, Elijah J; Tu, Xiaomin; Dizdaroglu, Miral; Zheng, Ming; Nelson, Bryant C

2013-01-28

The overall level of ultrasonication-induced DNA damage is reduced in the presence of single-wall carbon nanotubes (SWCNTs), particularly for DNA lesions formed by one-electron reduction of intermediate radicals. The protective role of SWCNTs observed in this work suggests a contrary view to the general idea that carbon nanotubes have damaging effects on biomolecules. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

DNA Replication Arrest and DNA Damage Responses Induced by Alkylating Minor Groove Binders

DTIC Science & Technology

2001-05-01

We are interested in the molecular mechanisms involved in DNA replication arrest by the S phase DNA damage checkpoints. Using in vitro simian virus...40 DNA replication assays, we have found three factors that directly contribute to DNA damage-induced DNA replication arrest: Replication Protein A...trans-acting inhibitors. RPA is the major eukaryotic single-stranded DNA binding protein required for DNA replication , repair and recombination. Upon DNA

Characteristics and mechanism of laser-induced surface damage initiated by metal contaminants

NASA Astrophysics Data System (ADS)

Shi, Shuang; Sun, Mingying; Shi, Shuaixu; Li, Zhaoyan; Zhang, Ya-nan; Liu, Zhigang

2015-08-01

In high power laser facility, contaminants on optics surfaces reduce damage resistance of optical elements and then decrease their lifetime. By damage test experiments, laser damage induced by typical metal particles such as stainless steel 304 is studied. Optics samples with metal particles of different sizes on surfaces are prepared artificially based on the file and sieve. Damage test is implemented in air using a 1-on-1 mode. Results show that damage morphology and mechanism caused by particulate contamination on the incident and exit surfaces are quite different. Contaminants on the incident surface absorb laser energy and generate high temperature plasma during laser irradiation which can ablate optical surface. Metal particles melt and then the molten nano-particles redeposit around the initial particles. Central region of the damaged area bears the same outline as the initial particle because of the shielding effect. However, particles on the exit surface absorb a mass of energy, generate plasma and splash lots of smaller particles, only a few of them redeposit at the particle coverage area on the exit surface. Most of the laser energy is deposited at the interface of the metal particle and the sample surface, and thus damage size on the exit surface is larger than that on the incident surface. The areas covered by the metal particle are strongly damaged. And the damage sites are more serious than that on the incident surface. Besides damage phenomenon also depends on coating and substrate materials.

Quantitative Evaluation of Hard X-ray Damage to Biological Samples using EUV Ptychography

NASA Astrophysics Data System (ADS)

Baksh, Peter; Odstrcil, Michal; Parsons, Aaron; Bailey, Jo; Deinhardt, Katrin; Chad, John E.; Brocklesby, William S.; Frey, Jeremy G.

2017-06-01

Coherent diffractive imaging (CDI) has become a standard method on a variety of synchrotron beam lines. The high brilliance short wavelength radiation from these sources can be used to reconstruct attenuation and relative phase of a sample with nanometre resolution via CDI methods. However, the interaction between the sample and high energy ionising radiation can cause degradation to sample structure. We demonstrate, using a laboratory based high harmonic generation (HHG) based extreme ultraviolet (EUV) source, imaging a sample of hippocampal neurons using the ptychography method. The significant increase in contrast of the sample in the EUV light allows identification of damage induced from exposure to 7.3 keV photons, without causing any damage to the sample itself.

RNA protects a nucleoprotein complex against radiation damage

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bury, Charles S.; McGeehan, John E.; Antson, Alfred A.

Radiation damage during macromolecular X-ray crystallographic data collection is still the main impediment for many macromolecular structure determinations. Even when an eventual model results from the crystallographic pipeline, the manifestations of radiation-induced structural and conformation changes, the so-called specific damage, within crystalline macromolecules can lead to false interpretations of biological mechanisms. Although this has been well characterized within protein crystals, far less is known about specific damage effects within the larger class of nucleoprotein complexes. We developed a methodology whereby per-atom density changes could be quantified with increasing dose over a wide (1.3–25.0 MGy) range and at higher resolution (1.98more » Å) than the previous systematic specific damage study on a protein–DNA complex. Specific damage manifestations were determined within the largetrpRNA-binding attenuation protein (TRAP) bound to a single-stranded RNA that forms a belt around the protein. Over a large dose range, the RNA was found to be far less susceptible to radiation-induced chemical changes than the protein. The availability of two TRAP molecules in the asymmetric unit, of which only one contained bound RNA, allowed a controlled investigation into the exact role of RNA binding in protein specific damage susceptibility. The 11-fold symmetry within each TRAP ring permitted statistically significant analysis of the Glu and Asp damage patterns, with RNA binding unexpectedly being observed to protect these otherwise highly sensitive residues within the 11 RNA-binding pockets distributed around the outside of the protein molecule. In addition, the method enabled a quantification of the reduction in radiation-induced Lys and Phe disordering upon RNA binding directly from the electron density.« less

RNA protects a nucleoprotein complex against radiation damage

DOE PAGES

Bury, Charles S.; McGeehan, John E.; Antson, Alfred A.; ...

2016-04-26

Radiation damage during macromolecular X-ray crystallographic data collection is still the main impediment for many macromolecular structure determinations. Even when an eventual model results from the crystallographic pipeline, the manifestations of radiation-induced structural and conformation changes, the so-called specific damage, within crystalline macromolecules can lead to false interpretations of biological mechanisms. Although this has been well characterized within protein crystals, far less is known about specific damage effects within the larger class of nucleoprotein complexes. We developed a methodology whereby per-atom density changes could be quantified with increasing dose over a wide (1.3–25.0 MGy) range and at higher resolution (1.98more » Å) than the previous systematic specific damage study on a protein–DNA complex. Specific damage manifestations were determined within the largetrpRNA-binding attenuation protein (TRAP) bound to a single-stranded RNA that forms a belt around the protein. Over a large dose range, the RNA was found to be far less susceptible to radiation-induced chemical changes than the protein. The availability of two TRAP molecules in the asymmetric unit, of which only one contained bound RNA, allowed a controlled investigation into the exact role of RNA binding in protein specific damage susceptibility. The 11-fold symmetry within each TRAP ring permitted statistically significant analysis of the Glu and Asp damage patterns, with RNA binding unexpectedly being observed to protect these otherwise highly sensitive residues within the 11 RNA-binding pockets distributed around the outside of the protein molecule. In addition, the method enabled a quantification of the reduction in radiation-induced Lys and Phe disordering upon RNA binding directly from the electron density.« less

On the relationship between indentation hardness and modulus, and the damage resistance of biological materials.

PubMed

Labonte, David; Lenz, Anne-Kristin; Oyen, Michelle L

2017-07-15

The remarkable mechanical performance of biological materials is based on intricate structure-function relationships. Nanoindentation has become the primary tool for characterising biological materials, as it allows to relate structural changes to variations in mechanical properties on small scales. However, the respective theoretical background and associated interpretation of the parameters measured via indentation derives largely from research on 'traditional' engineering materials such as metals or ceramics. Here, we discuss the functional relevance of indentation hardness in biological materials by presenting a meta-analysis of its relationship with indentation modulus. Across seven orders of magnitude, indentation hardness was directly proportional to indentation modulus. Using a lumped parameter model to deconvolute indentation hardness into components arising from reversible and irreversible deformation, we establish criteria which allow to interpret differences in indentation hardness across or within biological materials. The ratio between hardness and modulus arises as a key parameter, which is related to the ratio between irreversible and reversible deformation during indentation, the material's yield strength, and the resistance to irreversible deformation, a material property which represents the energy required to create a unit volume of purely irreversible deformation. Indentation hardness generally increases upon material dehydration, however to a larger extent than expected from accompanying changes in indentation modulus, indicating that water acts as a 'plasticiser'. A detailed discussion of the role of indentation hardness, modulus and toughness in damage control during sharp or blunt indentation yields comprehensive guidelines for a performance-based ranking of biological materials, and suggests that quasi-plastic deformation is a frequent yet poorly understood damage mode, highlighting an important area of future research. Instrumented

Prophylaxis with Bacopa monnieri attenuates acrylamide induced neurotoxicity and oxidative damage via elevated antioxidant function.

PubMed

Shinomol, George Kunnel; Raghunath, Narayanareddy; Bharath, Muchukunte Mukunda Srinivas; Muralidhara

2013-03-01

Acrylamide (ACR) is a water-soluble, vinyl monomer that has multiple chemical and industrial applications. Exposure to ACR causes neuropathy and associated neurological defects including gait abnormalities and skeletal muscle weakness, due to impaired neurotransmitter release and eventual neurodegeneration. Using in vivo and in vitro models, we examined whether oxidative events are involved in ACR-mediated neurotoxicity and whether these could be prevented by natural plant extracts. Administration (i.p.) of ACR in mice (40 mg/kg bw/ d for 5d) induced significant oxidative damage in the brain cortex and liver as evidenced by elevated lipid peroxidation, reactive oxygen species and protein carbonyls. This was associated with lowered antioxidant activities including antioxidant enzymes (catalase, glutathione-s-transferase) and reduced glutathione (GSH) compared to untreated controls. Similarly, exposure of N27 neuronal cells in culture to ACR (1-5 mM) caused dose-dependent neuronal death and lowered GSH. Interestingly, dietary supplementation with the leaf powder of Bacopa monnieri (BM) (which possesses neuroprotective properties and nootropic activity) in mice for 30 days offered significant protection against ACR toxicity and oxidative damage in vivo. Similarly, pretreatment with BM protected the N27 cells against ACR-induced cell death and associated oxidative damage. Co-treatment and pre-treatment of Drosophila melanogaster with BM extract protected against ACR-induced locomotor dysfunction and GSH depletion. We infer that BM displays prophylactic effects against ACR induced oxidative damage and neurotoxicity with potential therapeutic application in human pathology associated with neuropathy.

Protective Effect of Pyruvate Against Radiation-Induced Damage in Collagenized Tissues

NASA Technical Reports Server (NTRS)

Griko, Y. V.; Yan, Xiaoli

2016-01-01

Exposure to high doses of ionizing radiation produces both acute and late effects on the collagenized tissues and have profound effects on wound healing. Because of the crucial practical importance for new radioprotective agents, our study has been focused on evaluation of the efficacy of non-toxic naturally occurring compounds to protect tissue integrity against high-dose gamma radiation. Here, we demonstrate that molecular integrity of collagen may serve as a sensitive biological marker for quantitative evaluation of molecular damage to collagenized tissue and efficacy of radioprotective agents. Increasing doses of gamma radiation (0-50kGy) result in progressive destruction of the native collagen fibrils, which provide a structural framework, strength, and proper milieu for the regenerating tissue. The strategy used in this study involved the thermodynamic specification of all structural changes in collagenized matrix of skin, aortic heart valve, and bone tissue induced by different doses and conditions of g-irradiation. This study describes a simple biophysical approach utilizing the Differential Scanning Calorimetry (DSC) to characterize the structural resistance of the aortic valve matrix exposed to different doses of g-irradiation. It allows us to identify the specific response of each constituent as well as to determine the influence of the different treatments on the characteristic parameters of protein structure. We found that pyruvate, a substance that naturally occurs in the body, provide significant protection (up to 80%) from biochemical and biomechanical damage to the collagenized tissue through the effective targeting of reactive oxygen species. The recently discovered role of pyruvate in the cell antioxidant defense to O2 oxidation, and its essential constituency in the daily human diet, indicate that the administration of pyruvate-based radioprotective formulations may provide safe and effective protection from deleterious effects of ionizing

Gravity-induced rock mass damage related to large en masse rockslides: Evidence from Vajont

NASA Astrophysics Data System (ADS)

Paronuzzi, Paolo; Bolla, Alberto

2015-04-01

The Vajont landslide is a well-known, reservoir-induced slope failure that occurred on 9 October 1963 and was characterized by an 'en masse' sliding motion that triggered various large waves, determining catastrophic consequences for the nearby territory and adjacent villages. During the Vajont dam construction, and especially after the disaster, some researchers identified widespread field evidence of heavy rock mass damage involving the presumed prehistoric rockslide and/or the 1963 failed mass. This paper describes evidence of heavy gravitational damage, including (i) folding, (ii) fracturing, (iii) faulting, and (iv) intact rock disintegration. The gravity-induced rock mass damage (GRMD) characterizes the remnants of the basal shear zone, still resting on the large detachment surface, and the 1963 failed rock mass. The comprehensive geological study of the 1963 Vajont landslide, based on the recently performed geomechanical survey (2006-present) and on the critical analysis of the past photographic documentation (1959-1964), allows us to recognize that most GRMD evidence is related to the prehistoric multistage Mt. Toc rockslide. The 1963 catastrophic en masse remobilization induced an increase to the prehistoric damage, reworking preexisting structures and creating additional gravity-driven features (folds, fractures, faults, and rock fragmentation). The gravity-induced damage was formed during the slope instability phases that preceded the collapse (static or quasi-static GRMD) and also as a consequence of the sliding motion and of the devastating impact between the failed blocks (dynamic GRMD). Gravitational damage originated various types of small drag folds such as flexures, concentric folds, chevron, and kink-box folds, all having a radius of 1-5 m. Large buckle folds (radius of 10-50 m) are related to the dynamic damage and were formed during the en masse motion as a consequence of deceleration and impact processes that involved the sliding mass. Prior

Yields of biologically significant damage produced in mammalian DNA by irradiation associated with radon decay. Final progress report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ward, J.F.

1994-03-01

The objective of this project was to characterize the difference between damage to DNA caused by alpha particles and by low LET radiation. Estimation of the risk posed by exposure to high LET radiation (such as that from radon) relies at present on epidemiological data, and is therefore largely empirical. This empiricism is evident from the concepts of quality factor or RBE that find use for describing the biological effects of high LET radiation. The author argues that some effort should be made to address the mechanisms of DNA damage by high and low LET forms of radiation, and howmore » these mechanisms might relate to the biological endpoints. This report summarizes the results of the author`s investigations and the current understanding of these mechanisms.« less

Effective protection of biological membranes against photo-oxidative damage: Polymeric antioxidant forming a protecting shield over the membrane.

PubMed

Mertins, Omar; Mathews, Patrick D; Gomide, Andreza B; Baptista, Mauricio S; Itri, Rosangela

2015-10-01

We have prepared a chitosan polymer modified with gallic acid in order to develop an efficient protection strategy biological membranes against photodamage. Lipid bilayers were challenged with photoinduced damage by photosensitization with methylene blue, which usually causes formation of hydroperoxides, increasing area per lipid, and afterwards allowing leakage of internal materials. The damage was delayed by a solution of gallic acid in a concentration dependent manner, but further suppressed by the polymer at very low concentrations. The membrane of giant unilamellar vesicles was covered with this modified macromolecule leading to a powerful shield against singlet oxygen and thus effectively protecting the lipid membrane from oxidative stress. The results have proven the discovery of a promising strategy for photo protection of biological membranes. Copyright © 2015 Elsevier B.V. All rights reserved.

(WASHINGTON, DC) A FLUORESCENCE BASED ASSAY FOR DNA DAMAGE INDUCED BY TOXIC INDUSTRIAL CHEMICALS

EPA Science Inventory

Numerous natural and man-made agents are continuously released into the environment due to human activity. Many of these agents cause irreversible damage to the normal biological functions leading to morbidity and mortality in the exposed organisms. The possibility of deliberat...

Hepatoprotective effect of electrolyzed reduced water against carbon tetrachloride-induced liver damage in mice.

PubMed

Tsai, Chia-Fang; Hsu, Yu-Wen; Chen, Wen-Kang; Chang, Wen-Huei; Yen, Cheng-Chieh; Ho, Yung-Chyuan; Lu, Fung-Jou

2009-08-01

The study investigated the protective effect of electrolyzed reduced water (ERW) against carbon tetrachloride (CCl(4))-induced liver damage. Male ICR mice were randomly divided into control, CCl(4), CCl(4)+silymarin, and CCl(4)+ERW groups. CCl(4)-induced liver lesions include leukocytes infiltration, hepatocyte necrosis, ballooning degeneration, mitosis, calcification, fibrosis and an increase of serum alanine aminotransferase (ALT), and aminotransferase (AST) activity. In addition, CCl(4) also significantly decreased the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). By contrast, ERW or silymarin supplement significantly ameliorated the CCl(4)-induced liver lesions, lowered the serum levels of hepatic enzyme markers (ALT and AST) and increased the activities of SOD, catalase, and GSH-Px in liver. Therefore, the results of this study show that ERW can be proposed to protect the liver against CCl(4)-induced oxidative damage in mice, and the hepatoprotective effect might be correlated with its antioxidant and free radical scavenging effect.

Walnut polyphenols prevent liver damage induced by carbon tetrachloride and d-galactosamine: hepatoprotective hydrolyzable tannins in the kernel pellicles of walnut.

PubMed

Shimoda, Hiroshi; Tanaka, Junji; Kikuchi, Mitsunori; Fukuda, Toshiyuji; Ito, Hideyuki; Hatano, Tsutomu; Yoshida, Takashi

2008-06-25

The polyphenol-rich fraction (WP, 45% polyphenol) prepared from the kernel pellicles of walnuts was assessed for its hepatoprotective effect in mice. A single oral administration of WP (200 mg/kg) significantly suppressed serum glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) elevation in liver injury induced by carbon tetrachloride (CCl 4), while it did not suppress d-galactosamine (GalN)-induced liver injury. In order to identify the active principles in WP, we examined individual constituents for the protective effect on cell damage induced by CCl 4 and d-GalN in primary cultured rat hepatocytes. WP was effective against both CCl 4- and d-GalN-induced hepatocyte damages. Among the constituents, only ellagitannins with a galloylated glucopyranose core, such as tellimagrandins I, II, and rugosin C, suppressed CCl 4-induced hepatocyte damage significantly. Most of the ellagitannins including tellimagrandin I and 2,3- O-hexahydroxydiphenoylglucose exhibited remarkable inhibitory effect against d-GalN-induced damage. Telliamgrandin I especially completely suppressed both CCl 4- and d-GalN-induced cell damage, and thus is likely the principal constituent for the hepatoprotective effect of WP.

Hypothermia can reverse hepatic oxidative stress damage induced by hypoxia in rats.

PubMed

Garnacho-Castaño, Manuel Vicente; Alva, Norma; Sánchez-Nuño, Sergio; Bardallo, Raquel G; Palomeque, Jesús; Carbonell, Teresa

2016-12-01

Our previous findings demonstrated that hypothermia enhances the reduction potential in the liver and helps to maintain the plasmatic antioxidant pool. Here, we aimed to elucidate if hypothermia protects against hypoxia-induced oxidative stress damage in rat liver. Several hepatic markers of oxidative stress were compared in three groups of animals (n = 8 in each group): control normothermic group ventilated with room air and two groups under extreme hypoxia (breathing 10 % O 2 ), one kept at normothermia (HN) (37 °C) and the other under deep hypothermia (HH) (central body temperature of 21-22 °C). Hypoxia in normothermia significantly increased the levels of hepatic nitric oxide, inducible nitric oxide synthase expression, protein oxidation, Carbonilated proteins, advanced oxidation protein products, 4-hydroxynonenal (HNE) protein adducts, and lipid peroxidation when compared to the control group (p < 0.05). However, when hypoxia was induced under hypothermia, results from the oxidative stress biomarker analyses did not differ significantly from those found in the control group. Indeed, 4-HNE protein adduct amounts were significantly lower in the HH versus HN group (p < 0.05). Therefore, hypothermia can mitigate hypoxia-induced oxidative stress damage in rat liver. These effects could help clarify the mechanisms of action of therapeutic hypothermia.

Differential effects of experimental and cold-induced hyperthyroidism on factors inducing rat liver oxidative damage.

PubMed

Venditti, P; Pamplona, R; Ayala, V; De Rosa, R; Caldarone, G; Di Meo, S

2006-03-01

Thyroid hormone-induced increase in metabolic rates is often associated with increased oxidative stress. The aim of the present study was to investigate the contribution of iodothyronines to liver oxidative stress in the functional hyperthyroidism elicited by cold, using as models cold-exposed and 3,5,3'-triiodothyronine (T3)- or thyroxine (T4)-treated rats. The hyperthyroid state was always associated with increases in both oxidative capacity and oxidative damage of the tissue. The most extensive damage to lipids and proteins was found in T3-treated and cold-exposed rats, respectively. Increase in oxygen reactive species released by mitochondria and microsomes was found to contribute to tissue oxidative damage, whereas the determination of single antioxidants did not provide information about the possible contribution of a reduced effectiveness of the antioxidant defence system. Indeed, liver oxidative damage in hyperthyroid rats was scarcely related to levels of the liposoluble antioxidants and activities of antioxidant enzymes. Conversely, other biochemical changes, such as the degree of fatty acid unsaturation and hemoprotein content, appeared to predispose hepatic tissue to oxidative damage associated with oxidative challenge elicited by hyperthyroid state. As a whole, our results confirm the idea that T3 plays a key role in metabolic changes and oxidative damage found in cold liver. However, only data concerning changes in glutathione peroxidase activity and mitochondrial protein content favour the idea that dissimilarities in effects of cold exposure and T3 treatment could depend on differences in serum levels of T4.

Predictive analysis of thermal distribution and damage in thermotherapy on biological tissue

NASA Astrophysics Data System (ADS)

Fanjul-Vélez, Félix; Arce-Diego, José Luis

2007-05-01

The use of optical techniques is increasing the possibilities and success of medical praxis in certain cases, either in tissue characterization or treatment. Photodynamic therapy (PDT) or low intensity laser treatment (LILT) are two examples of the latter. Another very interesting implementation is thermotherapy, which consists of controlling temperature increase in a pathological biological tissue. With this method it is possible to provoke an improvement on specific diseases, but a previous analysis of treatment is needed in order for the patient not to suffer any collateral damage, an essential point due to security margins in medical procedures. In this work, a predictive analysis of thermal distribution in a biological tissue irradiated by an optical source is presented. Optical propagation is based on a RTT (Radiation Transport Theory) model solved via a numerical Monte Carlo method, in a multi-layered tissue. Data obtained are included in a bio-heat equation that models heat transference, taking into account conduction, convection, radiation, blood perfusion and vaporization depending on the specific problem. Spatial-temporal differential bio-heat equation is solved via a numerical finite difference approach. Experimental temperature distributions on animal tissue irradiated by laser radiation are shown. From thermal distribution in tissue, thermal damage is studied, based on an Arrhenius analysis, as a way of predicting harmful effects. The complete model can be used for concrete treatment proposals, as a way of predicting treatment effects and consequently decide which optical source parameters are appropriate for the specific disease, mainly wavelength and optical power, with reasonable security margins in the process.

Melatonin Protects Human Cells from Clustered DNA Damages, Killing and Acquisition of Soft Agar Growth Induced by X-rays or 970 MeV/n Fe ions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Das, B.; Sutherland, B.; Bennett, P. V.

We tested the ability of melatonin (N-acetyl-5 methoxytryptamine), a highly effective radical scavenger and human hormone, to protect DNA in solution and in human cells against induction of complex DNA clusters and biological damage induced by low or high linear energy transfer radiation (100 kVp X-rays, 970 MeV/nucleon Fe ions). Plasmid DNA in solution was treated with increasing concentrations of melatonin (0.0-3.5 mM) and were irradiated with X-rays. Human cells (28SC monocytes) were also irradiated with X-rays and Fe ions with and without 2 mM melatonin. Agarose plugs containing genomic DNA were subjected to Contour Clamped Homogeneous Electrophoretic Field (CHEF)more » followed by imaging and clustered DNA damages were measured by using Number Average length analysis. Transformation experiments on human primary fibroblast cells using soft agar colony assay were carried out which were irradiated with Fe ions with or without 2 mM melatonin. In plasmid DNA in solution, melatonin reduced the induction of single- and double-strand breaks. Pretreatment of human 28SC cells for 24 h before irradiation with 2 mM melatonin reduced the level of X-ray induced double-strand breaks by {approx}50%, of abasic clustered damages about 40%, and of Fe ion-induced double-strand breaks (41% reduction) and abasic clusters (34% reduction). It decreased transformation to soft agar growth of human primary cells by a factor of 10, but reduced killing by Fe ions only by 20-40%. Melatonin's effective reduction of radiation-induced critical DNA damages, cell killing, and striking decrease of transformation suggest that it is an excellent candidate as a countermeasure against radiation exposure, including radiation exposure to astronaut crews in space travel.« less

Evaluation of Cassia tora Linn. against Oxidative Stress-induced DNA and Cell Membrane Damage

PubMed Central

Kumar, R Sunil; Narasingappa, Ramesh Balenahalli; Joshi, Chandrashekar G; Girish, Talakatta K; Prasada Rao, Ummiti JS; Danagoudar, Ananda

2017-01-01

Objective: The present study aims to evaluate antioxidants and protective role of Cassia tora Linn. against oxidative stress-induced DNA and cell membrane damage. Materials and Methods: The total and profiles of flavonoids were identified and quantified through reversed-phase high-performance liquid chromatography. In vitro antioxidant activity was determined using standard antioxidant assays. The protective role of C. tora extracts against oxidative stress-induced DNA and cell membrane damage was examined by electrophoretic and scanning electron microscopic studies, respectively. Results: The total flavonoid content of CtEA was 106.8 ± 2.8 mg/g d.w.QE, CtME was 72.4 ± 1.12 mg/g d.w.QE, and CtWE was 30.4 ± 0.8 mg/g d.w.QE. The concentration of flavonoids present in CtEA in decreasing order: quercetin >kaempferol >epicatechin; in CtME: quercetin >rutin >kaempferol; whereas, in CtWE: quercetin >rutin >kaempferol. The CtEA inhibited free radical-induced red blood cell hemolysis and cell membrane morphology better than CtME as confirmed by a scanning electron micrograph. CtEA also showed better protection than CtME and CtWE against free radical-induced DNA damage as confirmed by electrophoresis. Conclusion: C. tora contains flavonoids and inhibits oxidative stress and can be used for many health benefits and pharmacotherapy. PMID:28584491

Investigation of Laser-Induced Retinal Damage: Wavelength and Pulsewidth Dependent Mechanisms

DTIC Science & Technology

1994-08-31

transformation. Biochim Biophys Acta 1991; 1072:129-57. 2. Artuc M, Ramshad M, Kappus H. Studies on acute toxic effects to keratinocytes induced by...hematoporphyrin derivatives and laser light Arch Dermatol Res 1989;281:491-4. 3. Artuc M, Ramshad M, Reinhold C, Kappus H. DNA damage caused by laser light

Effects of substrate on the femtosecond laser-induced damage properties of gold films

NASA Astrophysics Data System (ADS)

Huang, Haopeng; Wang, Leilei; Kong, Fanyu; Xia, Zhilin; Jin, Yunxia; Xu, Jiao; Chen, Junming; Cui, Yun; Shao, Jianda

2018-07-01

In this work, gold films on two different types of substrates were fabricated by electron beam (e-beam) evaporation, and the femtosecond laser-induced damage properties were evaluated. The first sample was gold film deposited on fused silica, whereas the second was gold deposited on photoresist. 1-on-1 damage tests were implemented by an 800 ± 30 nm laser with pulse duration of 30 fs. Different damage thresholds and morphologies were obtained for the two samples. The damage threshold of the gold film on fused silica was 0.64 J/cm2, with the typical damage morphology of thermal ablation and melting; the damage threshold of the gold film on photoresist was 0.30 J/cm2, with the typical damage morphology of blisters or peeling off. In order to better understand the impact of the substrate on the properties of the whole sample, the normalized electric field intensity, temperature, and thermal stress distributions were calculated. The adhesion between the gold film and substrate were measured and the experimental results well agreed with the theoretical analysis. The results indicate that gold films deposited onto grating-structured fused silica will have more powerful laser damage resistance performance.

Day and night variations in the repair of ionizing-radiation-induced DNA damage in mouse splenocytes.

PubMed

Palombo, Philipp; Moreno-Villanueva, Maria; Mangerich, Aswin

2015-04-01

In mammals, biological rhythms synchronize physiological and behavioral processes to the 24-h light-dark (LD) cycle. At the molecular level, self-sustaining processes, such as oscillations of transcription-translation feedback loops, control the circadian clock, which in turn regulates a wide variety of cellular processes, including gene expression and cell cycle progression. Furthermore, previous studies reported circadian oscillations in the repair capacity of DNA lesions specifically repaired by nucleotide excision repair (NER). However, it is so far only poorly understood if DNA repair pathways other than NER are under circadian control, in particular base excision and DNA strand break repair. In the present study, we analyzed potential day and night variations in the repair of DNA lesions induced by ionizing radiation (i.e., mainly oxidative damage and DNA strand breaks) in living mouse splenocytes using a modified protocol of the automated FADU assay. Our results reveal that splenocytes isolated from mice during the light phase (ZT06) displayed higher DNA repair activity than those of the dark phase (ZT18). As analyzed by highly sensitive and accurate qPCR arrays, these alterations were accompanied by significant differences in expression profiles of genes involved in the circadian clock and DNA repair. Notably, the majority of the DNA repair genes were expressed at higher levels during the light phase (ZT06). This included genes of all major DNA repair pathways with the strongest differences observed for genes of base excision and DNA double strand break repair. In conclusion, here we provide novel evidence that mouse splenocytes exhibit significant differences in the repair of IR-induced DNA damage during the LD cycle, both on a functional and on a gene expression level. It will be interesting to test if these findings could be exploited for therapeutic purposes, e.g. time-of-the-day-specific application of DNA-damaging treatments used against blood

Delayed repair of radiation induced clustered DNA damage: Friend or foe?

PubMed Central

Eccles, Laura J.; O’Neill, Peter; Lomax, Martine E.

2011-01-01

A signature of ionizing radiation exposure is the induction of DNA clustered damaged sites, defined as two or more lesions within one to two helical turns of DNA by passage of a single radiation track. Clustered damage is made up of double strand breaks (DSB) with associated base lesions or abasic (AP) sites, and non-DSB clusters comprised of base lesions, AP sites and single strand breaks. This review will concentrate on the experimental findings of the processing of non-DSB clustered damaged sites. It has been shown that non-DSB clustered damaged sites compromise the base excision repair pathway leading to the lifetime extension of the lesions within the cluster, compared to isolated lesions, thus the likelihood that the lesions persist to replication and induce mutation is increased. In addition certain non-DSB clustered damaged sites are processed within the cell to form additional DSB. The use of E. coli to demonstrate that clustering of DNA lesions is the major cause of the detrimental consequences of ionizing radiation is also discussed. The delayed repair of non-DSB clustered damaged sites in humans can be seen as a “friend”, leading to cell killing in tumour cells or as a “foe”, resulting in the formation of mutations and genetic instability in normal tissue. PMID:21130102

Nuclear aggregates of polyamines in a radiation-induced DNA damage model.

PubMed

Iacomino, Giuseppe; Picariello, Gianluca; Stillitano, Ilaria; D'Agostino, Luciano

2014-02-01

Polyamines (PA) are believed to protect DNA minimizing the effect of radiation damage either by inducing DNA compaction and aggregation or acting as scavengers of free radicals. Using an in vitro pDNA double strand breakage assay based on gel electrophoretic mobility, we compared the protective capability of PA against γ-radiation with that of compounds generated by the supramolecular self-assembly of nuclear polyamines and phosphates, named Nuclear Aggregates of Polyamines (NAPs). Both unassembled PA and in vitro produced NAPs (ivNAPs) were ineffective in conferring pDNA protection at the sub-mM concentration. Single PA showed an appreciable protective effect only at high (mM) concentrations. However, concentrations of spermine (4+) within a critical range (0.481 mM) induced pDNA precipitation, an event that was not observed with NAPs-pDNA interaction. We conclude that the interaction of individual PA is ineffective to assure DNA protection, simultaneously preserving the flexibility and charge density of the double strand. Furthermore, data obtained by testing polyamine and ivNAPS with the current radiation-induced DNA damage model support the concept that PA-phosphate aggregates are the only forms through which PA interact with DNA. Copyright © 2013 Elsevier Ltd. All rights reserved.

Predicting moisture-induced damage to asphaltic concrete : field evaluation phase, interim report.

DOT National Transportation Integrated Search

1977-01-01

Virginia is one of seven state and federal agencies participating in a field evaluation of a stripping test method developed under NCHRP Project 4-8 (3), "Predicting Moisture- Induced Damage to Asphaltic Concrete." The test method is being used to ev...

Molecular mechanisms of phoxim-induced silk gland damage and TiO2 nanoparticle-attenuated damage in Bombyx mori.

PubMed

Li, Bing; Yu, Xiaohong; Gui, Suxin; Xie, Yi; Zhao, Xiaoyang; Hong, Jie; Sun, Qingqing; Sang, Xuezi; Sheng, Lei; Cheng, Zhe; Cheng, Jie; Hu, Rengping; Wang, Ling; Shen, Weide; Hong, Fashui

2014-06-01

Phoxim is a useful organophosphate (OP) pesticide used in agriculture in China, however, exposure to this pesticide can result in a significant reduction in cocooning in Bombyx mori (B. mori). Titanium dioxide nanoparticles (TiO2 NPs) have been shown to decrease phoxim-induced toxicity in B. mori; however, very little is known about the molecular mechanisms of silk gland damage due to OP exposure and repair of gland damage by TiO2 NP pretreatment. In the present study, exposure to phoxim resulted in a significant reduction in cocooning rate in addition to silk gland damage, whereas TiO2 NP attenuated phoxim-induced gland damage, increased the antioxidant capacity of the gland, and increased cocooning rate in B. mori. Furthermore, digital gene expression data suggested that phoxim exposure led to significant alterations in the expression of 833 genes. In particular, phoxim exposure caused significant down-regulation of Fib-L, Ser2, Ser3, and P25 genes involved in silk protein synthesis, and up-regulation of SFGH, UCH3, and Salhh genes involved in silk protein hydrolysis. A combination of both phoxim and TiO2 NP treatment resulted in marked changes in the expression of 754 genes, while treatment with TiO2 NPs led to significant alterations in the expression of 308 genes. Importantly, pretreatment with TiO2 NPs increased Fib-L, Ser2, Ser3, and P25 expression, and decreased SFGH, UCH3, and Salhh expression in silk protein in the silk gland under phoxim stress. Therefore, Fib-L, Ser2, Ser3, P25, SFGH, UCH3, and Salhh may be potential biomarkers of silk gland toxicity in B. mori caused by phoxim exposure. Copyright © 2013 Elsevier Ltd. All rights reserved.

Chemotherapy-induced bystander effect in response to several chloroethylnitrosoureas: an origin independent of DNA damage?

PubMed

Merle, Patrick; Morvan, Daniel; Caillaud, Denis; Demidem, Aicha

2008-01-01

Chloroethylnitrosourea (CENU) chemotherapy is used for the treatment of melanoma tumors. The main mechanism of action of this anticancer agent is via DNA damage. We recently showed in murine experiments using a parental double B16 melanoma tumor model that, after treatment of primary tumors with cystemustine (CENU agent), untreated secondary tumors exhibited growth inhibition and metabolism disorders. The response of secondary untreated tumor was called the chemotherapy-induced bystander effect. To see whether chemotherapy-induced bystander effects were induced with other members of the CENU family, we compared three CENU(s) used in melanoma treatment: cystemustine, carmustine and fotemustine. Our results demonstrate that fotemustine, like cystemustine, but not carmustine induced a protective effect against secondary untreated tumors including alterations in phospholipid derivative and glutathione which are the metabolic signature of the bystander effect. From these data we may conclude that DNA damage to the primary tumor is not sufficient to explain chemotherapy-induced bystander effects.

Environmental-Induced Damage in Tin (Sn) and Aluminum (Al) Alloys

NASA Astrophysics Data System (ADS)

Vallabhaneni, Venkata Sathya Sai Renuka

Sn and Al alloys are widely used in various industries. Environmental-induced damage resulting in whiskering in Sn and corrosion in Al account for numerous failures globally every year. Therefore, for designing materials that can better withstand these failures, a comprehensive study on the characterization of the damage is necessary. This research implements advanced characterization techniques to study the above-mentioned environmental-induced damage in Sn and Al alloys. Tin based films are known to be susceptible to whisker growth resulting in numerous failures. While the mechanisms and factors affecting whisker growth have been studied extensively, not much has been reported on the mechanical properties of tin whiskers themselves. This study focuses on the tensile behavior of tin whiskers. Tensile tests of whiskers were conducted in situ a dual beam focused ion beam (FIB) with a scanning electron microscope (SEM) using a micro electro-mechanical system (MEMS) tensile testing stage. The deformation mechanisms of whiskers were analyzed using transmission electron microscopy (TEM). Due to the heterogenous nature of the microstructure of Al 7075, it is susceptible to corrosion forming corrosion products and pits. These can be sites for cracks nucleation and propagation resulting in stress corrosion cracking (SCC). Therefore, complete understanding of the corrosion damaged region and its effect on the strength of the alloy is necessary. Several studies have been performed to visualize pits and understand their effect on the mechanical performance of Al alloys using two-dimensional (2D) approaches which are often inadequate. To get a thorough understanding of the pits, it is necessary for three-dimensional (3D) studies. In this study, Al 7075 alloys were corroded in 3.5 wt.% NaCl solution and X-ray tomography was used to obtain the 3D microstructure of pits enabling the quantification of their dimensions accurately. Furthermore, microstructure and mechanical property

New method for measuring the laser-induced damage threshold of optical thin film

NASA Astrophysics Data System (ADS)

Su, Jun-hong; Wang, Hong; Xi, Ying-xue

2012-10-01

The laser-induced damage threshold (LIDT) of thin film means that the thin film can withstand a maximum intensity of laser radiation. The film will be damaged when the irradiation under high laser intensity is greater than the value of LIDT. In this paper, an experimental platform with measurement operator interfaces and control procedures in the VB circumstance is built according to ISO11254-1. In order to obtain more accurate results than that with manual measurement, in the software system, a hardware device can be controlled by control widget on the operator interfaces. According to the sample characteristic, critical parameters of the LIDT measurement system such as spot diameter, damage threshold region, and critical damage pixel number are set up on the man-machine conversation interface, which could realize intelligent measurements of the LIDT. According to experimental data, the LIDT is obtained by fitting damage curve automatically.

Acute hydrodynamic damage induced by SPLITT fractionation and centrifugation in red blood cells.

PubMed

Urbina, Adriana; Godoy-Silva, Ruben; Hoyos, Mauricio; Camacho, Marcela

2016-05-01

Though blood bank processing traditionally employs centrifugation, new separation techniques may be appealing for large scale processes. Split-flow fractionation (SPLITT) is a family of techniques that separates in absence of labelling and uses very low flow rates and force fields, and is therefore expected to minimize cell damage. However, the hydrodynamic stress and possible consequent damaging effects of SPLITT fractionation have not been yet examined. The aim of this study was to investigate the hydrodynamic damage of SPLITT fractionation to human red blood cells, and to compare these effects with those induced by centrifugation. Peripheral whole blood samples were collected from healthy volunteers. Samples were diluted in a buffered saline solution, and were exposed to SPLITT fractionation (flow rates 1-10 ml/min) or centrifugation (100-1500 g) for 10 min. Cell viability, shape, diameter, mean corpuscular hemoglobin, and membrane potential were measured. Under the operating conditions employed, both SPLITT and centrifugation maintained cell viability above 98%, but resulted in significant sublethal damage, including echinocyte formation, decreased cell diameter, decreased mean corpuscular hemoglobin, and membrane hyperpolarization which was inhibited by EGTA. Wall shear stress and maximum energy dissipation rate showed significant correlation with lethal and sublethal damage. Our data do not support the assumption that SPLITT fractionation induces very low shear stress and is innocuous to cell function. Some changes in SPLITT channel design are suggested to minimize cell damage. Measurement of membrane potential and cell diameter could provide a new, reliable and convenient basis for evaluation of hydrodynamic effects on different cell models, allowing identification of optimal operating conditions on different scales. Copyright © 2016 Elsevier B.V. All rights reserved.

Laser-induced bulk damage of silica glass at 355nm and 266nm

NASA Astrophysics Data System (ADS)

Kashiwagi, R.; Aramomi, S.

2016-12-01

Laser processing machines using Nd:YAG 3rd harmonic wave (355 nm) and 4th harmonic wave (266 nm) have been developed and put into practical use lately. Due to this, optical elements with high laser durability to 355 nm and 266 nm are required. Silica glass is the optical element which has high UV transmission and high laser durability. Laser-induced surface damage of the silica glass has been studied in detail, but we hardly have the significant knowledge of laserinduced bulk damage. This knowledge is required in order to evaluate the silica glass itself. That is because cracks and scratches on the surface give rise to a higher possibility of damage. Therefore, we studied the laser durability of a variety of the silica glass samples by 1-on-1 and S-on-1 laser-induced bulk damage threshold (LIDT) at 355 nm and 266 nm. In this study, we gained knowledge in three areas about bulk damage to the silica glass. First, the LIDT became lower as shot counts increased. Second, the LIDT decreased as the hydroxyl content in the silica glass increased. Last, the LIDT became higher as the hydrogen concentration in the silica glass increased. Under the UV irradiation, impurities are generated and the silica glass absorbs more light. Therefore, the LIDT decreased as shot counts increased. Also, the hydroxyl in particular generates more impurities, so damage easily occurs. On the other hand, the hydrogen reacts with impurities and absorption is suppressed. Based on these results, we can improve laser durability at 355 nm and 266 nm by reducing the hydroxyl content and increasing the hydrogen concentration in the silica glass.

DNA damage-induced nuclear translocation of Apaf-1 is mediated by nucleoporin Nup107

PubMed Central

Jagot-Lacoussiere, Léonard; Faye, Audrey; Bruzzoni-Giovanelli, Heriberto; Villoutreix, Bruno O; Rain, Jean-Christophe; Poyet, Jean-Luc

2015-01-01

Beside its central role in the mitochondria-dependent cell death pathway, the apoptotic protease activating factor 1 (Apaf-1) is involved in the DNA damage response through cell-cycle arrest induced by genotoxic stress. This non-apoptotic function requires a nuclear translocation of Apaf-1 during the G1-to-S transition. However, the mechanisms that trigger the nuclear accumulation of Apaf-1 upon DNA damage remain to be investigated. Here we show that the main 4 isoforms of Apaf-1 can undergo nuclear translocation and restore Apaf-1 deficient MEFs cell cycle arrest in the S phase following genotoxic stress through activation of Chk-1. Interestingly, DNA damage-dependent nuclear accumulation of Apaf-1 occurs independently of p53 and the retinoblastoma (pRb) pathway. We demonstrated that Apaf-1 associates with the nucleoporin Nup107 and this association is necessary for Apaf-1 nuclear import. The CED-4 domain of Apaf-1 directly binds to the central domain of Nup107 in an ATR-regulated, phosphorylation-dependent manner. Interestingly, expression of the Apaf-1-interacting domain of Nup107 interfered with Apaf-1 nuclear translocation upon genotoxic stress, resulting in a marked reduction of Chk-1 activation and cell cycle arrest. Thus, our results confirm the crucial role of Apaf-1 nuclear relocalization in mediating cell-cycle arrest induced by genotoxic stress and implicate Nup107 as a critical regulator of the DNA damage-induced intra-S phase checkpoint response. PMID:25695197

REC-2006—A Fractionated Extract of Podophyllum hexandrum Protects Cellular DNA from Radiation-Induced Damage by Reducing the Initial Damage and Enhancing Its Repair In Vivo

PubMed Central

Chaudhary, Pankaj; Shukla, Sandeep Kumar; Sharma, Rakesh Kumar

2011-01-01

Podophyllum hexandrum, a perennial herb commonly known as the Himalayan May Apple, is well known in Indian and Chinese traditional systems of medicine. P. hexandrum has been widely used for the treatment of venereal warts, skin infections, bacterial and viral infections, and different cancers of the brain, lung and bladder. This study aimed at elucidating the effect of REC-2006, a bioactive fractionated extract from the rhizome of P. hexandrum, on the kinetics of induction and repair of radiation-induced DNA damage in murine thymocytes in vivo. We evaluated its effect on non-specific radiation-induced DNA damage by the alkaline halo assay in terms of relative nuclear spreading factor (RNSF) and gene-specific radiation-induced DNA damage via semi-quantitative polymerase chain reaction. Whole body exposure of animals with gamma rays (10 Gy) caused a significant amount of DNA damage in thymocytes (RNSF values 17.7 ± 0.47, 12.96 ± 1.64 and 3.3 ± 0.014) and a reduction in the amplification of β-globin gene to 0, 28 and 43% at 0, 15 and 60 min, respectively. Administrating REC-2006 at a radioprotective concentration (15 mg kg−1 body weight) 1 h before irradiation resulted in time-dependent reduction of DNA damage evident as a decrease in RNSF values 6.156 ± 0.576, 1.647 ± 0.534 and 0.496 ± 0.012, and an increase in β-globin gene amplification 36, 95 and 99%, at 0, 15 and 60 min, respectively. REC-2006 scavenged radiation-induced hydroxyl radicals in a dose-dependent manner stabilized DPPH free radicals and also inhibited superoxide anions. Various polyphenols and flavonoides present in REC-2006 might contribute to scavenging of radiation-induced free radicals, thereby preventing DNA damage and stimulating its repair. PMID:20008078

Coptidis Rhizoma Prevents Heat Stress-Induced Brain Damage and Cognitive Impairment in Mice

PubMed Central

Moon, Minho; Huh, Eugene; Song, Eun Ji; Hwang, Deok-Sang; Lee, Tae Hee; Oh, Myung Sook

2017-01-01

Heat stress conditions lead to neuroinflammation, neuronal death, and memory loss in animals. Coptidis Rhizoma (CR) exhibits potent fever-reducing effects and has been used as an important traditional medicinal herb for treating fever. However, to date, the effects of antipyretic CR on heat-induced brain damages have not been investigated. In this study, CR significantly reduced the elevation of ear and rectal temperatures after exposure to heat in mice. Additionally, CR attenuated hyperthermia-induced stress responses, such as release of cortisol into the blood, and upregulation of heat shock protein and c-Fos in the hypothalamus and hippocampus of mice. The administration of CR inhibited gliosis and neuronal loss induced by thermal stress in the hippocampal CA3 region. Treatment with CR also reduced the heat stress-induced expression of nuclear factor kappa β, tumor necrosis factor-α, and interleukin-1β (IL-1β) in the hippocampus. Moreover, CR significantly decreased proinflammatory mediators such as IL-9 and IL-13 in the heat-stressed hypothalamus. Furthermore, CR attenuated cognitive dysfunction triggered by thermal stress. These results indicate that CR protects the brain against heat stress-mediated brain damage via amelioration of hyperthermia and neuroinflammation in mice, suggesting that fever-reducing CR can attenuate thermal stress-induced neuropathology. PMID:28946610

Effects of melatonin on spinal cord injury-induced oxidative damage in mice testis.

PubMed

Yuan, X-C; Wang, P; Li, H-W; Wu, Q-B; Zhang, X-Y; Li, B-W; Xiu, R-J

2017-09-01

This study evaluated the effects of melatonin on spinal cord injury (SCI)-induced oxidative damage in testes. Adult male C57BL/6 mice were randomly divided into sham-, SCI- or melatonin (10 mg/kg, i.p.)-treated SCI groups. To induce SCI, a standard weight-drop method that induced a contusion injury at T10 was used. After 1 week, testicular blood flow velocity was measured using the Laser Doppler Line Scanner. Malondialdehyde (MDA), glutathione (GSH), oxidised glutathione (GSSG) and myeloperoxidase (MPO) were measured in testis homogenates. Microvascular permeability of the testes to Evan's Blue was examined by spectrophotometric and fluorescence microscopic quantitation. The tight junction protein zonula occludens-1 (ZO-1) and occludin in testes were assessed by immunoblot analysis. Melatonin increased the reduced blood flow and decreased SCI-induced permeability of capillaries. MDA levels and MPO activity were elevated in the SCI group compared with shams, which was reversed by melatonin. In contrast, SCI-induced reductions in GSH/GSSG ratio were restored by melatonin. Decreased expression of ZO-1 and occludin was observed, which was attenuated by melatonin. Overall, melatonin treatment protects the testes against oxidative stress damage caused by SCI. © 2016 Blackwell Verlag GmbH.

Optical control of filamentation-induced damage to DNA by intense, ultrashort, near-infrared laser pulses

PubMed Central

Dharmadhikari, J. A.; Dharmadhikari, A. K.; Kasuba, K. C.; Bharambe, H.; D’Souza, J. S.; Rathod, K. D.; Mathur, D.

2016-01-01

We report on damage to DNA in an aqueous medium induced by ultrashort pulses of intense laser light of 800 nm wavelength. Focusing of such pulses, using lenses of various focal lengths, induces plasma formation within the aqueous medium. Such plasma can have a spatial extent that is far in excess of the Rayleigh range. In the case of water, the resulting ionization and dissociation gives rise to in situ generation of low-energy electrons and OH-radicals. Interactions of these with plasmid DNA produce nicks in the DNA backbone: single strand breaks (SSBs) are induced as are, at higher laser intensities, double strand breaks (DSBs). Under physiological conditions, the latter are not readily amenable to repair. Systematic quantification of SSBs and DSBs at different values of incident laser energy and under different external focusing conditions reveals that damage occurs in two distinct regimes. Numerical aperture is the experimental handle that delineates the two regimes, permitting simple optical control over the extent of DNA damage. PMID:27279565

Effects of Traumeel (Tr14) on Exercise-Induced Muscle Damage Response in Healthy Subjects: A Double-Blind RCT

PubMed Central

Deuster, Vanessa; Frech, Torsten; Pons-Kühnemann, Jörn; Mooren, Frank-Christoph

2016-01-01

The present double-blind, randomized, placebo-controlled clinical trial intended to test whether ingestion of a natural combination medicine (Tr14 tablets) affects serum muscle damage and inflammatory immune response after downhill running. 96 male subjects received Tr14 tablets, which consist of 14 diluted biological and mineral components, or a placebo for 72 h after the exercise test, respectively. Changes in postexercise levels of various serum muscle damage and immunological markers were investigated. The area under the curve with respect to the increase (AUCi) of perceived pain score and creatine kinase (CK) were defined as primary outcome measures. While for CK the p value of the difference between the two groups is borderline, the pain score and muscle strength were not statistically significant. However, a trend towards lower levels of muscle damage (CK, p = 0.05; LDH, p = 0.06) in the Tr14 group was shown. Less pronounced lymphopenia (p = 0.02), a trend towards a lower expression of CD69 count (p = 0.07), and antigen-stimulated ICAM-1 (p = 0.01) were found in the verum group. The Tr14 group showed a tendentially lower increase of neutrophils (p = 0.10), BDNF (p = 0.03), stem cell factor (p = 0.09), and GM-CSF (p = 0.09) to higher levels. The results of the current study indicate that Tr14 seems to limit exercise-induced muscle damage most likely via attenuation of both innate and adaptive immune responses. This study was registered with ClinicalTrials.gov (NCT01912469). PMID:27478305

Effects of Traumeel (Tr14) on Exercise-Induced Muscle Damage Response in Healthy Subjects: A Double-Blind RCT.

PubMed

Muders, Kerstin; Pilat, Christian; Deuster, Vanessa; Frech, Torsten; Krüger, Karsten; Pons-Kühnemann, Jörn; Mooren, Frank-Christoph

2016-01-01

The present double-blind, randomized, placebo-controlled clinical trial intended to test whether ingestion of a natural combination medicine (Tr14 tablets) affects serum muscle damage and inflammatory immune response after downhill running. 96 male subjects received Tr14 tablets, which consist of 14 diluted biological and mineral components, or a placebo for 72 h after the exercise test, respectively. Changes in postexercise levels of various serum muscle damage and immunological markers were investigated. The area under the curve with respect to the increase (AUCi) of perceived pain score and creatine kinase (CK) were defined as primary outcome measures. While for CK the p value of the difference between the two groups is borderline, the pain score and muscle strength were not statistically significant. However, a trend towards lower levels of muscle damage (CK, p = 0.05; LDH, p = 0.06) in the Tr14 group was shown. Less pronounced lymphopenia (p = 0.02), a trend towards a lower expression of CD69 count (p = 0.07), and antigen-stimulated ICAM-1 (p = 0.01) were found in the verum group. The Tr14 group showed a tendentially lower increase of neutrophils (p = 0.10), BDNF (p = 0.03), stem cell factor (p = 0.09), and GM-CSF (p = 0.09) to higher levels. The results of the current study indicate that Tr14 seems to limit exercise-induced muscle damage most likely via attenuation of both innate and adaptive immune responses. This study was registered with ClinicalTrials.gov (NCT01912469).

MHY1485 ameliorates UV-induced skin cell damages via activating mTOR-Nrf2 signaling.

PubMed

Yang, Bo; Xu, Qiu-Yun; Guo, Chun-Yan; Huang, Jin-Wen; Wang, Shu-Mei; Li, Yong-Mei; Tu, Ying; He, Li; Bi, Zhi-Gang; Ji, Chao; Cheng, Bo

2017-02-21

Ultra Violet (UV)-caused skin cell damage is a main cause of skin cancer. Here, we studied the activity of MHY1485, a mTOR activator, in UV-treated skin cells. In primary human skin keratinocytes, HaCaT keratinocytes and human skin fibroblasts, MHY1485 ameliorated UV-induced cell death and apoptosis. mTOR activation is required for MHY1485-induced above cytoprotective actions. mTOR kinase inhibitors (OSI-027, AZD-8055 and AZD-2014) or mTOR shRNA knockdown almost abolished MHY1485-induced cytoprotection. Further, MHY1485 treatment in skin cells activated mTOR downstream NF-E2-related factor 2 (Nrf2) signaling, causing Nrf2 Ser-40 phosphorylation, stabilization/upregulation and nuclear translocation, as well as mRNA expression of Nrf2-dictated genes. Contrarily, Nrf2 knockdown or S40T mutation almost nullified MHY1485-induced cytoprotection. MHY1485 suppressed UV-induced reactive oxygen species production and DNA single strand breaks in skin keratinocytes and fibroblasts. Together, we conclude that MHY1485 inhibits UV-induced skin cell damages via activating mTOR-Nrf2 signaling.

Agmatine protects against cell damage induced by NMDA and glutamate in cultured hippocampal neurons

PubMed Central

Wang, Wei-Ping; Iyo, Abiye H.; Miguel-Hidalgo, Javier; Regunathan, Soundar; Zhu, Meng-Yang

2010-01-01

Agmatine is a polyamine and has been considered as a novel neurotransmitter or neuromodulator in the central nervous system. In the present study, the neuroprotective effect of agmatine against cell damage caused by N-methyl-d-aspartate (NMDA) and glutamate was investigated in cultured rat hippocampal neurons. Lactate dehydrogenase (LDH) activity assay, β-tubulin III immunocytochemical staining and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP) nick end-labeling (TUNEL) assay were conducted to detect cell damage. Exposure of 12-day neuronal cultures of rat hippocampus to NMDA or glutamate for 1 h caused a concentration-dependent neurotoxicity, as indicated by the significant increase in released LDH activities. Addition of 100 µM agmatine into media ablated the neurotoxicity induced by NMDA or glutamate, an effect also produced by the specific NMDA receptor antagonist dizocilpine hydrogen maleate (MK801). Arcaine, an analog of agmatine with similar structure as agmatine, fully prevented the NMDA- or glutamate-induced neuronal damage. Spermine and putrescine, the endogenous polyamine and metabolic products of agmatine without the guanidine moiety of agmatine, failed to show this effect, indicating a structural relevance for this neuroprotection. Immunocytochemical staining and TUNEL assay confirmed the findings in the LDH measurement. That is, agmatine and MK801 markedly attenuated NMDA-induced neuronal death and significantly reduced TUNEL-positive cell numbers induced by exposure of cultured hippocampal neurons to NMDA. Taken together, these results demonstrate that agmatine can protect cultured hippocampal neurons from NMDA- or glutamate-induced excitotoxicity, through a possible blockade of the NMDA receptor channels or a potential anti-apoptotic property. PMID:16546145

Induction and repair of HZE induced cytogenetic damage

NASA Technical Reports Server (NTRS)

Brooks, A. L.; Bao, S.; Rithidech, K.; Chrisler, W. B.; Couch, L. A.; Braby, L. A.

2001-01-01

Wistar rats were exposed to high-mass, high energy (HZE) 56Fe particles (1000 GeV/AMU) using the Alternating Gradient Synchrotron (AGS). The animals were sacrificed at 1-5 hours or after a 30-day recovery period. The frequency of micronuclei in the tracheal and the deep lung epithelial cells were evaluated. The relative effectiveness of 56Fe, for the induction of initial chromosome damage in the form of micronuclei, was compared to damage produced in the same biological system exposed to other types of high and low-LET radiation. It was demonstrated that for animals sacrificed at short times after exposure, the tracheal and lung epithelial cells, the 56Fe particles were 3.3 and 1.3 times as effective as 60Co in production of micronuclei, respectively. The effectiveness was also compared to that for exposure to inhaled radon. With this comparison, the 56Fe exposure of the tracheal epithelial cells and the lung epithelial cells were only 0.18 and 0.20 times as effective as radon in the production of the initial cytogenetic damage. It was suggested that the low relative effectiveness was related to potential for 'wasted energy' from the core of the 56Fe particles. When the animals were sacrificed after 30 days, the slopes of the dose-response relationships, which reflect the remaining level of damage, decreased by a factor of 10 for both the tracheal and lung epithelial cells. In both cases, the slope of the dose-response lines were no longer significantly different from zero, and the r2 values were very high. Lung epithelial cells, isolated from the animals sacrificed hours after exposure, were maintained in culture, and the micronuclei frequency evaluated after 4 and 6 subcultures. These cells were harvested at 24 and 36 days after the exposure. There was no dose-response detected in these cultures and no signs of genomic instability at either sample time.