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V Vallyathan

Publications and source records attributed to V Vallyathan.

At least 73 records · Page 4Linked to original sources
PubMed1999

Effects of pirfenidone on the generation of reactive oxygen species in vitro.

Pirfenidone is a newly developed antifibrotic drug that has been reported to retard the progression of pulmonary fibrosis induced by bleomycin and cyclophosphamide in animal models of lung fibrosis. The present in vitro studies using noncellular and cellular systems evaluated the antioxidant and cytotoxic properties of this drug. The Fenton reaction [Fe(II) + H2O2 --> Fe(III) + *OH + OH-] and the xanthine/xanthine oxidase system were used as sources of hydroxyl (*OH) and superoxide anion (O2*-) radicals, respectively. Electron spin resonance spin trapping was used for free radical detection and measurement. The reaction rate of pirfenidone with *OH was found to be 1.63 x 10(10) M(-1) s(-1), which is comparable to several well-established antioxidants, such as ascorbate, glutathione, cysteine, azide, and lipoic acid. Compared to *OH radicals, the O2*- scavenging was less efficient 42.36 M(-1) s(-1) with pirfenidone. Pirfenidone was also effective in inhibiting zymosan-stimulated chemiluminescence. In a noncellular model of lipid peroxidation, pirfenidone inhibited crystalline silica-induced lipid peroxidation. The inhibition of crystalline silica-induced cytotoxic reactions and lipid peroxidation combined with the efficient antioxidant properties of pirfenidone indicate that this agent may express its antifibrotic effects partly through its ability to scavenge reactive oxygen species.

Animals↗
PubMed1998

Scavenging of reactive oxygen species by melatonin.

The direct effects of the neurohormone melatonin on reactive oxygen species (ROS) were investigated. Melatonin was found to inhibit DMPO-O-2 formation in a dose-dependent manner. At the level of 1. 7+/-0.07 mM, melatonin caused 50% inhibition of EPR signal intensity of DMPO-O-2 during the reaction of xanthine and xanthine oxidase. The reaction rate constant of melatonin with O2- was found to be 1.25+/-0.07x103 M-1 s-1. However, melatonin (up to 1.2 mM) did not exhibit significant effect toward OH radical, produced by the Fenton reaction. In addition, we found no evidence for the formation of the melatonin indolyl cation radical that presumably precedes conversion of melatonin to its stable N1-acetyl-N2-5-methoxykynuramine (AMK) metabolite following sequential reactions of melatonin with O2- and OH. On the other hand, melatonin was capable of scavenging H2O2 in a dose-dependent manner with an IC50=0.5+/-0.02 mM. The reaction rate constant of melatonin with H2O2 was found to be 2.52+/-0.19x105 M-1 s-1. Furthermore, melatonin was also found to inhibit 1O2-dependent 2,2,6,6-tetramethylpiperidine oxide (TEMPO) radical formation during rose bengal photodynamic reaction. The results suggest that melatonin's antioxidant properties, in part, may involve a direct effect on scavenging of ROS.

Antioxidants↗
PubMed1998

Antioxidant activity of lazaroid (U-75412E) and its protective effects against crystalline silica-induced cytotoxicity.

Lazaroids (21-amino steroids) are believed to be powerful scavengers of reactive oxygen species (ROS) and inhibitors of lipid peroxidation. Crystalline silica, a potent cytotoxic agent, causes pulmonary fibrosis in experimental animals and humans. ROS have been previously shown to be involved in crystalline silica-induced pulmonary injury and inflammation. In the present study, the reaction rate of lazaroid (U-75412E) with hydroxyl radical (.OH) generated by Fenton reaction (Fe(II) + H2O2 --> Fe(III) + OH- + .OH) was investigated using ESR spin-trapping competition reactions. The reaction rate constant was found to be 1.0 x 10(10) M(-1)s(-1), which was comparable with those of other efficient .OH radical scavengers. As indicators of crystalline silica-induced cytotoxicity and its protection by this antioxidant lazaroid (U-75412E) we measured lactate dehydrogenase, N-acetyl-beta-glucosaminidase, superoxide dismutase, glutathione peroxidase, and hydrogen peroxide released from rat alveolar macrophages. Lipid peroxidation, a prominent manifestation of .OH radical-induced cell injury, was also measured to evaluate the protective value of lazaroid. Alveolar macrophages treated with lazaroid (U-75412E) before crystalline silica exposure were protected against cell injury and lipid peroxidation as demonstrated by those indicators. Lazaroid (U-75412E) scavenges .OH radicals generated by crystalline silica-mediated reaction from H2O2 and inhibits lipid peroxidation in macrophages induced by these particles.

Animals↗
PubMed1998

Cobalt-mediated generation of reactive oxygen species and its possible mechanism.

Electron spin resonance spin trapping was utilized to investigate free radical generation from cobalt (Co) mediated reactions using 5,5-dimethyl-1-pyrroline (DMPO) as a spin trap. A mixture of Co with water in the presence of DMPO generated 5,5-dimethylpyrroline-(2)-oxy(1) DMPOX, indicating the production of strong oxidants. Addition of superoxide dismutase (SOD) to the mixture produced hydroxyl radical (.OH). Catalase eliminated the generation of this radical and metal chelators, such as desferoxamine, diethylenetriaminepentaacetic acid or 1,10-phenanthroline, decreased it. Addition of Fe(II) resulted in a several fold increase in the .OH generation. UV and O2 consumption measurements showed that the reaction of Co with water consumed molecular oxygen and generated Co(II). Since reaction of Co(II) with H2O2 did not generate any significant amount of .OH radicals, a Co(I) mediated Fenton-like reaction [Co(I) + H2O2-->Co(II) + .OH + OH-] seems responsible for .OH generation. H2O2 is produced from O2.- via dismutation, O2.- is produced by one-electron reduction of molecular oxygen catalyzed by Co. Chelation of Co(II) by biological chelators, such as glutathione or beta-ananyl-3-methyl-L-histidine alters, its oxidation-reduction potential and makes Co(II) capable of generating .OH via a Co(II)-mediated Fenton-like reaction [Co(II) + H2O2-->Co(III) + .OH + OH-]. Thus, the reaction of Co with water, especially in the presence of biological chelators, glutathione, glycylglycylhistidine and beta-ananyl-3-methyl-L-histidine, is capable of generating a whole spectrum of reactive oxygen species, which may be responsible for Co-induced cell injury.

Catalase↗
PubMed1998

Reactive oxygen species: their relation to pneumoconiosis and carcinogenesis.

Occupational exposures to mineral particles cause pneumoconiosis and other diseases, including cancer. Recent studies have suggested that reactive oxygen species (ROS) may play a key role in the mechanisms of disease initiation and progression following exposure to these particles. ROS-induced primary stimuli result in the increased secretion of proinflammatory cytokines and other mediators, promoting events that appear to be important in the progression of cell injury and pulmonary disease. We have provided evidence supporting the hypothesis that inhalation of insoluble particles such as asbestos, agricultural dusts, coal, crystalline silica, and inorganic dust can be involved in facilitating multiple pathways for persistent generation of ROS, which may lead to a continuum of inflammation leading to progression of disease. This article briefly summarizes some of the recent findings from our laboratories with emphasis on the molecular events by which ROS are involved in promoting pneumoconiosis and carcinogenesis.

Animals↗
PubMed1997

Oxidative stress in silicosis: evidence for the enhanced clearance of free radicals from whole lungs.

We hypothesized that reactive oxygen species (ROS) may be involved in the pathogenesis of silicosis. To investigate ROS' dependent pathophysiological processes during silicosis we studied the kinetic clearance of instilled stable nitroxide radicals (TEMPO). Antioxidant enzymes' superoxide dismutase (SOD) and glutathione peroxidase (GPx), and lipid peroxidation were also studied in whole lungs of rats exposed to crystalline silica (quartz) and sham exposed controls. Low frequency L-band electron spin resonance spectroscopy was used to measure the clearance of TEMPO in whole-rat lungs directly. The clearance of TEMPO followed first order kinetics showing significant differences in the rate for clearance between the diseased and sham exposed control lungs. Comparison of TEMPO clearance rates in the sham exposed controls and silicotic rats showed an oxidative stress in the rats exposed to quartz. Studies on the antioxidant enzymes SOD and GPx in the lungs of silicotic and sham exposed animals supported the oxidative stress and accelerated clearance of TEMPO by up regulated levels of enzymes in quartz exposed animals. Increased lipid peroxidation potential in the silicotics also supported a role for enhanced generation of ROS in the pathogenesis of silica-induced lung injury. These in vivo experiments directly demonstrate, for the first time, that silicotic lungs are in a state of oxidative stress and that increased generation of ROS is associated with enhanced levels of oxidative enzymes and lipid peroxidation. This technique offers great promise for the elucidation of ROS induced lung injury and development of therapeutic strategies for the prevention of damage.

Animals↗
PubMed1997

Exposure and mineralogical correlates of pulmonary fibrosis in chrysotile asbestos workers.

OBJECTIVES: The relation between lifetime cumulative exposure to asbestos, pathological grade of pulmonary fibrosis, and lung burden of asbestos at death, was explored in a necropsy population of former workers in a chrysotile asbestos textile plant in South Carolina. METHODS: Estimates of cumulative, mean, and peak exposures to asbestos were available for 54 workers. Necropsy records and lung tissue samples were obtained from hospital files. Matched control cases were selected from consecutive necropsies performed at the same hospitals. The extent and severity of pulmonary fibrosis was graded on tissue sections. Mineral fibres in lung tissue were characterised by transmission electron microscopy combined with x ray spectroscopy. RESULTS: A significant positive correlation (r = 0.67, P < 0.0001) was found between lifetime cumulative exposure to asbestos and total lung burden of asbestos fibres. This relation was also found for the individual types of asbestos associated with the exposure: chrysotile and tremolite. Pulmonary fibrosis was correlated with both cumulative exposure to asbestos (r = 0.60, P < 0.01) and the concentration of asbestos fibres in the lung (r = 0.62, P < 0.0001). The concentration of tremolite fibres in the lung provided a better estimate of lung fibrosis than did the concentration of chrysotile. Asbestosis was usually present in asbestos textile workers with more than 20 fibre-years cumulative exposure. The lengths and aspect ratios of chrysotile asbestos, but not amphibole asbestos, were greater in the lungs of asbestos fibre workers than in the control population. Textile workers with lung cancer had significantly greater cumulative exposures and fibrosis scores than workers without lung cancer. CONCLUSIONS: Both cumulative exposure to asbestos and lung fibre burden are strongly correlated with severity of asbestosis. The data also support the hypothesis that the high prevalence of asbestosis and lung cancer in this population resulted from exposure to long fibres of chrysotile asbestos in the workplace.

Asbestos, Serpentine↗
PubMed1997

The role of oxygen free radicals in occupational and environmental lung diseases.

Oxygen free radicals and their metabolites, collectively described as reactive oxygen species (ROS), have been implicated in the pathogenesis of many diseases. The pulmonary system is particularly vulnerable to ROS-induced injury because of its continuous exposure to toxic pollutants from a wide variety of sources in the ambient air. Additionally, lungs are exposed systemically to ROS generated from xenobiotic compounds and endogenous sources. This review describes the sources of endogenous and exogenous ROS generation in the lung. Special emphasis is given to major sources of ROS in occupational and environmental exposures to asbestos, crystalline silica, coal, chromium, herbicides, bleomycin, and cigarette smoke. ROS-induced lung injury at different target levels may contribute to similar patterns of cell injury and alterations at the molecular level by initiation, propagation, and autocatalytic chain reactions. Intracellular signalling, activation and inactivation of enzymes, stimulation, secretion, and release of proinflammatory cytokines, chemokines, and nuclear factor activation and alterations are also common events. Understanding the interactions of these intricate mechanistic events is important in the prevention and amelioration of lung injury that results from acute and chronic exposures to toxins in ambient air.

Environmental Exposure↗
PubMed1997

Augmentation of pulmonary reactions to quartz inhalation by trace amounts of iron-containing particles.

Fracturing quartz produces silica-based radicals on the fracture planes and generates hydroxyl radicals (.OH) in aqueous media. .OH production has been shown to be directly associated with quartz-induced cell damage and phagocyte activation in vitro. This .OH production in vitro is inhibited by desferrioxamine mesylate, an Fe chelator, indicating involvement of a Fenton-like reaction. Our objective was to determine if Fe contamination increased the ability of inhaled quartz to cause inflammation and lung injury. Male Fischer 344 rats were exposed 5 hr/day for 10 days to filtered air, 20 mg/m3 freshly milled quartz (57 ppm Fe), or 20 mg/m3 freshly milled quartz contaminated with Fe (430 ppm Fe). High Fe contamination of quartz produced approximately 57% more reactive species in water than quartz with low Fe contamination. Compared to inhalation of quartz with low Fe contamination, high Fe contamination of quartz resulted in increases in the following responses: leukocyte recruitment (537%), lavageable red blood cells (157%), macrophage production of oxygen radicals measured by electron spin resonance or chemiluminescence (32 or 90%, respectively), nitric oxide production by macrophages (71%), and lipid peroxidation of lung tissue (38%). These results suggest that inhalation of freshly fractured quartz contaminated with trace levels of Fe may be more pathogenic than inhalation of quartz alone.

Administration, Inhalation↗
PubMed1996

Reduction of lung dust burden in pneumoconiosis by whole-lung lavage.

Pneumoconioses are characterized as irreversible, progressive respiratory diseases. No effective therapy exists to prevent progression of these diseases. Whole-lung lavage (WLL) might limit the rate of disease progression through the removal of dust, inflammatory cells, and cytokines. We performed WLL on a 54-year-old underground miner employed as a motorman and roof bolter and a 55-year-old driller at a surface coal mine. Both demonstrated normal lung function and chest radiographs showing ILO profusion category 2 nodular interstitial changes. From Subject 1, we recovered 5.24 x 10(8) cells (90% macrophages) from the right lung and 3.45 x 10(8) cells (94% macrophages) from the left lung. WLL removed 1.82 g of mineral dust (non-coal) on the right and 1.64 g on the left. From Subject 2, we recovered 7.49 x 10(8) cells (46% macrophages) from the right and 9.78 x 10(8) cells (69% macrophages) from the left lung. WLL removed 0.40 g of mineral dust on the right and 0.53 g on the left. Proinflammatory cytokines, growth factors, and cellular enzymes were also recovered. In cases of pneumoconiosis, WLL is capable of removing relatively large quantities of dust, cells, and soluble materials from the lungs. Only long-term follow-ups of individuals with progressive dust-induced disease who receive WLL therapy in the context of a clinical trial will provide information regarding the importance of removing mineral dust and inflammatory cells from the lung.

Bronchoalveolar Lavage↗
PubMed1996

Radiographic and pathologic correlation of coal workers' pneumoconiosis.

The relationships between chest radiographs (CXR) and corresponding pathology were investigated in 430 autopsied coal miners from West Virginia. Whole-lung sections were reviewed and graded on four-point severity scales for the following lesions of coal workers' pneumoconiosis (CWP): macules, micro- and macronodules (small and large fibrotic nodules), and progressive massive fibrosis (PMF). Antemortem CXR were classified by three B readers using the 1971 International Labor Office (ILO) U/C classification (6). On pathologic examination, 96% of miners had macules, 70% micronodules, 45% macronodules, 15% silicosis, and 28% PMF. By CXR, 69% of the miners had small, rounded opacity profusions of category > or = 0/1. Data analysis revealed increasing odds that small opacities of category > or = 0/1 would be detected with increasing grade of nodules. Profusion category 0/0 was often reported for cases with macules of mild to moderate grade and mild levels of micronodules. Overall, q-type opacities were associated with macules and micronodules, whereas the large r-type opacities were associated with macronodules. By CXR, large opacities showed good correlation with pathologic PMF. However, about one-third of cases identified as having large opacities by CXR were not substantiated as PMF by pathology. One-fourth of these cases could be explained by lung lesions such as Caplan's nodules, tuberculosis scars, and tumors. Similarly, 22% of cases classified as PMF on pathology had no large opacities by CXR. In half of these cases, the radiologists had noted other abnormalities (cancer, tuberculosis) by CXR as large opacities. Overall, the study showed good agreement (Somer's d = 0.64) between the predicted probabilities and observed responses of a profusion category > or = 0/1 for pathologic CWP lesions. However, the study also showed that CXR were insensitive for detecting minimal CWP lesions, and were unreliable indicators in the presence of concomitant pulmonary pathology.

Adult↗
PubMed1995

Hydroxyl radical generation by coal mine dust: possible implication to coal workers' pneumoconiosis (CWP).

Occupational exposure to coal mine dust causes coal workers' pneumoconiosis (CWP) and other pulmonary diseases by mechanisms that remain unclear. Because the hydroxyl radicals (.OH) may play an important role in the pathogenesis of CWP, we studied the potential role of bituminous coal mine dust samples for catalyzing the generation of .OH from hydrogen peroxide (H2O2). These coal mine dusts evaluated represented two geographic areas with diversity in CWP prevalence. Electron spin resonance (ESR), with the aid of spin trapping techniques, was used to measure the .OH radical generation. Bituminous coal mine dusts representing the Pittsburgh seam in the eastern United States and Blind Canyon seam in the mid-western United States were used together with a standard coal dust obtained from the National Institute of Standards and Technology, Gaithersburg, MD. All the coal mine dust samples generated varying levels of .OH radicals from H2O2 in the presence of a .OH spin trap 5,5-dimethyl-l-pyrroline-N-oxide (DMPO). .OH radical generation by the coal from H2O2 was effectively inhibited by deferoxamine and catalase, but only partially inhibited by superoxide dismutase. Metal chelators DETAPAC and EDTA enhanced the radical generation. These results indicated that the Fenton reaction is predominantly involved in the generation of .OH radicals from H2O2. The .OH-generating potential of all the coal dusts showed a positive correlation with the surface iron content of coal mine dusts. In addition, the potential to induce lipid peroxidation by the coal samples exhibited a good correlation with the available surface iron. Based on the results presented here, we propose that higher concentrations of surface iron in coal mine dust may be involved in the generation of increased levels of .OH radicals and may play an important role in the development of CWP in different coal mining areas.

Chelating Agents↗
PubMed1995

Antioxidant activity of tetrandrine and its inhibition of quartz-induced lipid peroxidation.

Tetrandrine is a benzylisoquinoline alkaloid that has been used in China as an antifibrotic drug to treat the lesions of silicosis. Its mechanism in the treatment of silicosis is unclear. Electron spin resonance (ESR) spin trapping was employed to investigate the antioxidant properties of tetrandrine. The spin trap used was 5,5-dimethyl-1-pyrroline N-oxide (DMPO). Tetrandine efficiently reacted with hydroxyl (.OH) radicals with a reaction rate of approximately 1.4 x 10(10) M-1 s-1. The .OH radicals were generated by the Fenton reaction [Fe(II) + H2O2) as well as by reaction of chromium(V) with H2O2. Similar results were obtained using .OH radicals generated by reaction of freshly fractured quartz particles with aqueous medium. Tetrandrine also scavenged superoxide (O2-) radicals produced from xanthine/xanthine oxidase. The effect of tetrandrine on lipid peroxidation induced by freshly fractured quartz particles was evaluated using linoleic acid as a model lipid. The results showed that tetrandrine caused a significant inhibition on freshly fractured quartz-induced lipid peroxidation.

Alkaloids↗
PubMed1995

Freshly fractured quartz inhalation leads to enhanced lung injury and inflammation. Potential role of free radicals.

Silicosis is a devastating pulmonary disease that continues to occur in industrial workplaces. Its pathogenesis is under critical evaluation, and this report provides new concepts on the possible early events that occur in lungs resulting from the inhalation of freshly fractured versus aged quartz in the development of two diverse disease entities. In this study, we evaluated the biochemical and pathologic changes in the lavagate and lungs of rats exposed to freshly fractured quartz (generated by jet milling), aged quartz (milled then aged for 2 mo prior to use), or clean air 5 h a day for 10 d over a 2-wk period. The concentration of crystalline quartz in the chambers averaged 20 mg/m3. Particle concentrations and particle size were similar for the freshly milled and aged quartz exposures. However, free radical concentrations associated with the freshly milled quartz samples were significantly higher than those for aged quartz. After a 2-wk exposure, animals were killed and studied by bronchoalveolar lavage and pulmonary histopathology. Inhalation of aged quartz increased the number of bronchoalveolar lavage cells, demonstrated histopathologic evidence of increased pulmonary infiltrates, showed enhanced concentrations of biochemical markers of lung injury, increased lipid peroxidation, and the ability of pulmonary phagocytes to produce more oxygen radicals. In general, all these pulmonary responses were significantly more pronounced after inhalation of freshly fractured quartz compared with aged quartz. In contrast, antioxidant enzymes showed decreased concentrations in the freshly fractured quartz-exposed group compared with the aged quartz-exposed animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Changes in alveolar lavage materials and lung microsomal xenobiotic metabolism following exposures to HCl-washed or unwashed crystalline silica.

Intratracheal exposures of rats to crystalline silica washed with HCl to remove iron contaminants have previously been shown to increase lung surfactant phospholipids (PL) and proteins and to alter the pulmonary microsomal cytochrome P450 system. We compared these effects of HCl-washed silica with those produced by exposures to unwashed silica and alumina. Both silica preparations produce increases in lung weights and alveolar lavage PL and proteins, but to different degrees. The increases produced by HCl-washed vs unwashed silica are lung weights, 2.2- vs 1.3-fold; lavage PL, 25.9- vs 3.7-fold; and lavage proteins, 11.1- vs 3.2-fold, respectively. Although the two silica particles increase lung microsomal protein concentrations (expressed per gram lung) by 50-60%, their effects on cytochrome P-450-mediated xenobiotic metabolism are quite different. Exposure to HCl-washed silica leads to a 2.3-fold increase in 7-ethoxyresorufin O-deethylation, a reaction catalyzed by cytochrome P4501A1, and a 0.5- to 0.6-fold reduction in 7-ethoxycoumarin O-deethylation, a reaction which may be catalyzed by cytochrome P-4502B1. Unwashed silica does not alter the metabolism of either xenobiotic when results are expressed per milligram microsomal protein. Administration of alumina produces only minor increases in lung weight and lavage PL and no effect on microsomal xenobiotic metabolism. These results show that the increases in alveolar lavage PL and proteins induced by administration of unwashed silica are exaggerated by 3- to 7-fold if the silica is treated with HCl. Furthermore, exposure to HCl-washed silica results in significant alterations of the lung microsomal cytochrome P450 system, but the unwashed silica has little effect. Although the reason(s) for these different effects is not known, measurements of iron levels and formation of hydroxyl radicals using ESR demonstrate that there is more iron associated with the unwashed than with the HCl-washed silica.

Animals↗
PubMed1994

Generation of oxygen radicals by minerals and its correlation to cytotoxicity.

Occupational exposure to mineral dust causes pneumoconiosis and other diseases. A cytotoxicity assay to predict the potential of minerals to cause disease would be of great value as a prevention strategy. This study compares the ability of several minerals to generate the more potent oxidizing agent, hydroxyl radical (.OH), and their cytotoxicity and lipid peroxidation potentials. Crystalline silica, the most potent cytotoxic and pathogenic mineral studied, showed the least ability to generate .OH radicals while inducing the maximal lipid peroxidation. Coal mine dust, showing the maximal ability to generate .OH radicals, was the least cytotoxic in bioassays of toxicity and induction of lipid peroxidation. Based on these results, it would appear that the ability of minerals to induce lipid peroxidation provides a better correlation with known cytotoxicity and pathogenicity of minerals than does their ability to generate oxygen radicals.

Animals↗
PubMed1994

Silica radical-induced DNA damage and lipid peroxidation.

In recent years, more attention has been given to the mechanism of disease induction caused by the surface properties of minerals. In this respect, specific research needs to be focused on the biologic interactions of oxygen radicals generated by mineral particles resulting in cell injury and DNA damage leading to fibrogenesis and carcinogenesis. In this investigation, we used electron spin resonance (ESR) and spin trapping to study oxygen radical generation from aqueous suspensions of freshly fractured crystalline silica. Hydroxyl radical (.OH), superoxide radical (O2.-) and singlet oxygen (1O2) were all detected. Superoxide dismutase (SOD) partially inhibited .OH yield, whereas catalase abolished .OH generation. H2O2 enhanced .OH generation while deferoxamine inhibited it, indicating that .OH is generated via a Haber-Weiss type reaction. These spin trapping measurements provide the first evidence that aqueous suspensions of silica particles generate O2.- and 1O2. Oxygen consumption measurements indicate that freshly fractured silica uses molecular oxygen to generate O2.- and 1O2. Electrophoretic assays of in vitro DNA strand breakages showed that freshly fractured silica induced DNA strand breakage, which was inhibited by catalase and enhanced by H2O2. In an argon atmosphere, DNA damage was suppressed, showing that molecular oxygen is required for the silica-induced DNA damage. Incubation of freshly fractured silica with linoleic acid generated linoleic acid-derived free radicals and caused dose-dependent lipid peroxidation as measured by ESR spin trapping and malondialdehyde formation. SOD, catalase, and sodium benzoate inhibited lipid peroxidation by 49, 52, and 75%, respectively, again showing the role of oxygen radicals in silica-induced lipid peroxidation.(ABSTRACT TRUNCATED AT 250 WORDS)

DNA Damage↗