Mattagajasingh S N, Misra H P
Department of Biomedical Sciences, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg 24061-0442, USA.
Mol Cell Biochem. 1995 Jan 12;142(1):61-70. doi: 10.1007/BF00928914.
The involvement of reactive oxygen species in chromate-induced genotoxicity has been postulated. Because intracellular antioxidants help in eliminating the reactive species of oxygen, we have investigated both the prooxidant and antioxidant status of human leukemic T-lymphocyte MOLT4 cells exposed to nontoxic levels of chromium(VI) in culture. The cells treated with 0-->200 microM potassium chromate in a salts/glucose medium for 2 h were found to contain significantly lower levels of both small molecular weight and macromolecular antioxidants. In particular, the levels of glutathione and ascorbate were found to decrease with increased doses of chromate exposure in a dose-dependent manner. As little as 10 microM chromate was found to decrease these small molecular weight antioxidants significantly (p < 0.01). The macromolecular antioxidants, such as glutathione peroxidase, catalase, glutathione reductase, glucose-6-phosphate dehydrogenase and superoxide dismutase were also significantly (p < 0.01) decreased by exposing the cells to as little as 10 microM chromate. Concomitantly, there was a dose-dependent increase in intracellular H2O2 accumulation in cells exposed to chromium(VI). These results indicate that chromate-induced genotoxicity may be due, at least in part, to decreased levels of intracellular antioxidants in conjunction with an increased production of the reactive oxygen species.
活性氧物种参与铬酸盐诱导的遗传毒性这一观点已被提出。由于细胞内抗氧化剂有助于清除活性氧物种,我们研究了在培养中暴露于无毒水平六价铬的人白血病T淋巴细胞MOLT4细胞的促氧化剂和抗氧化剂状态。发现在盐/葡萄糖培养基中用0至200微摩尔铬酸钾处理2小时的细胞,其小分子和大分子抗氧化剂水平均显著降低。特别是,谷胱甘肽和抗坏血酸的水平被发现随着铬酸盐暴露剂量的增加而呈剂量依赖性降低。仅10微摩尔的铬酸盐就被发现能显著降低这些小分子抗氧化剂的水平(p < 0.01)。将细胞暴露于仅10微摩尔的铬酸盐时,大分子抗氧化剂,如谷胱甘肽过氧化物酶、过氧化氢酶、谷胱甘肽还原酶、葡萄糖-6-磷酸脱氢酶和超氧化物歧化酶也显著(p < 0.01)降低。与此同时,暴露于六价铬的细胞内过氧化氢积累呈剂量依赖性增加。这些结果表明,铬酸盐诱导的遗传毒性可能至少部分归因于细胞内抗氧化剂水平的降低以及活性氧物种产生的增加。