MUTAGENESIS BY FREE RADICALS FROM BISULFITE AND THIOLS

亚硫酸氢盐和硫醇的自由基引起的诱变

• 批准号: 3918636
• 负责人: E ZEIGER
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3918636
• 关键词: cysteine; dipeptides; esters; free radicals; glutathione; glycine; hydrogen peroxide; mutagens; oxidation; penicillamine; thiols

The mutagenicities of sodium bisulfite and glutathione, reported earlier, appear to be mediated through the formation of oxygen- containing free radicals. The mutagenicity of bisulfite to bacteria is related to its autoxidation rate in solution, and this value varies with pH, temperature, and presence of other substances in solution with sodium bisulfite. The autoxidation rate changes with pH and temperature (pH 7/37C more than pH 7/27C more than pH 5/37C more than pH 5/27C) and the mutagenic response increases as the rate decreases. The data suggest that for mutagenicity to occur, unoxidized bisulfite must be available to be taken up by the cells. The addition of ethanol, mannitol liver homogenate (S9), or oxoid broth enhanced the responses but did not change the directions of the trends. These data suggest a role for sulfur and radicals in the toxicity and mutagenicity of bisulfite. Glutathione is mutagenic to bacteria via its autoxidation which leads to the formation of hydrogen peroxide, which is a bacterial mutagen. The Salmonella strains that are most responsive to glutathione mutagenicity are also the most responsive to hydrogen peroxide. Other thiols (cysteine, penicillamine, cysteine ethyl ester, and cysteinylglycine) were mutagenic without exogenous metabolic activation and their mutagenicity was a function of the pH of the medium and the pKa of the thiol group. This supports the hypothesis that the spontaneous oxidation of these thiols, with the eventual formation of hydrogen peroxide, requires the initial formation of a thiolate anion.

据报道，亚硫酸氢钠和谷胱甘肽的致突变性 早些时候，似乎是通过氧的形成介导的 含有自由基。 亚硫酸氢盐的致突变性 细菌的存在与其在溶液中的自氧化速率有关，这 值随 pH、温度和其他物质的存在而变化 与亚硫酸氢钠溶液。 自氧化速率变化 与 pH 值和温度（pH 7/37C 大于 pH 7/27C 大于 pH 5/37C 高于 pH 5/27C)，诱变反应随着 率下降。 数据表明，致突变性 发生时，未氧化的亚硫酸氢盐必须能够被 细胞。 添加乙醇、甘露醇肝匀浆(S9)， 或 oxoid 肉汤增强了反应，但没有改变 趋势的方向。 这些数据表明硫的作用 以及亚硫酸氢盐的毒性和致突变性中的自由基。 谷胱甘肽通过其自动氧化作用对细菌产生诱变作用， 导致过氧化氢的形成，这是一种细菌 诱变剂。 最敏感的沙门氏菌菌株 谷胱甘肽致突变性也是对氢最敏感的 过氧化物。 其他硫醇（半胱氨酸、青霉胺、半胱氨酸乙基 酯和半胱氨酰甘氨酸）在没有外源的情况下具有诱变性 代谢激活及其致突变性是 介质的 pH 值和硫醇基团的 pKa。 这支持 假设这些硫醇会自发氧化 最终形成过氧化氢，需要初始 硫醇盐阴离子的形成。