DNA damage by bromate: Mechanism and consequences
DNA damage by bromate: Mechanism and consequences
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DOI：
10.1016/j.tox.2006.01.009
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发表时间：
2006-04-17
期刊：
影响因子：
4.5
通讯作者：
Epe, B
中科院分区：
文献类型：
--
作者：
Ballmaier, D;Epe, B
哺乳动物细胞暴露于溴酸盐（BrO 3-）会产生氧化性DNA修饰，特别是7，8-二氢-8-氧代鸟嘌呤（8-oxoG）。破坏机制是非常独特的，因为谷胱甘肽，这是对大多数氧化剂和烷化剂的保护，介导的代谢活化，而溴酸盐本身不直接与DNA反应。在活化中不需要酶或过渡金属作为催化剂。最终的DNA破坏物质尚未确定，但在无细胞条件下的实验表明，既不涉及分子溴，也不涉及活性氧物质，如超氧化物，过氧化氢或单线态氧。相反，溴自由基（Br-中心点）或氧化物（BrO中心点，BrO 2中心点）可能是负责的。与次氯酸盐（ClO-）相比，溴酸盐的细胞毒性要小得多，这可能是因为前者能有效地与蛋白质和其他至关重要的细胞成分反应。因此，在溴酸盐的非细胞毒性浓度下，很容易检测到氧化性DNA损伤以及突变和微核的诱导，而次氯酸盐的DNA损伤仅在细胞毒性浓度下观察到，并遵循非线性（曲棍球棒样）剂量反应。(c)2006年Aww研究基金会。由Elsevier爱尔兰有限公司出版。保留所有权利。
Exposure of mammalian cells to bromate (BrO3-) generates oxidative DNA modifications, in particular 7,8-dihydro-8-oxoguanine (8-oxoG). The damaging mechanism is quite unique, since glutathione, which is protective against most oxidants and alkylating agents, mediates a metabolic activation, while bromate itself does not react directly with DNA. Neither enzymes nor transition metals are required as catalysts in the activation. The ultimate DNA damaging species has not yet been established, but experiments under cell-free conditions suggest that neither molecular bromine nor reactive oxygen species such as superoxide, hydrogen peroxide or singlet oxygen are involved. Rather bromine radicals (Br-center dot) or oxides (BrO center dot, BrO2 center dot) might be responsible. Compared to hypochlorite (ClO-), bromate is much less cytotoxic, probably because the former halite efficiently reacts with proteins and other vitally important cellular constituents. In consequence, oxidative DNA damage and the induction of mutations and micronuclei is easily detectable at non-cytotoxic concentrations of bromate, while DNA damage by hypochlorite is observed only at cytotoxic concentrations and follows a non-linear (hockey-stick-like) dose response. (c) 2006 Aww Research Foundation. Published by Elsevier Ireland Ltd. All rights reserved.