GLUTATHIONE-DEPENDENT TOXICITY
GLUTATHIONE-DEPENDENT TOXICITY
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DOI：
10.3109/00498259209051867
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发表时间：
1992-09-01
期刊：
影响因子：
1.8
通讯作者：
VAMVAKAS, S
中科院分区：
文献类型：
--
作者：
ANDERS, MW;DEKANT, W;VAMVAKAS, S
1.最近的研究表明，谷胱甘肽结合物的形成是一个重要的生物激活机制，为几组化合物的器官选择性毒性和致癌性的影响.邻位二卤代烷，如1，2-二卤代乙烷，产生S-（2-卤代烷基）谷胱甘肽共轭物，产生高度亲电的表锍离子，参与1，2-二卤代乙烷的细胞毒性和致突变性。3.肾毒性卤代烯烃代谢为S-（卤代烯基）-或S-（卤代烷基）-谷胱甘肽缀合物，其在代谢为相应的半胱氨酸缀合物后，被肾半胱氨酸缀合物β-裂解酶生物活化，产生细胞毒性或致突变代谢物。最后，肝谷胱甘肽与氢醌和氨基酚形成缀合物，产生针对富含γ-谷氨酰转移酶的组织（如肾脏）的缀合物，在那里它们经历烷基化或氧化还原循环反应，或两者，引起器官选择性损伤。
1. Recent studies show that glutathione conjugate formation is an important bioactivation mechanism for several groups of compounds with implications for organ-selective toxicity and carcinogenicity.2. Vicinal dihaloalkanes, such as 1,2-dihaloethanes, yield S-(2-haloalkyl)glutathione conjugates that give rise to highly electrophilic episulphonium ions, which are involved in the cytotoxicity and mutagenicity of 1,2-dihaloethanes.3. Nephrotoxic haloalkenes are metabolized to S-(haloalkenyl)- or S-(haloalkyl)-glutathione conjugates which, after metabolism to the corresponding cysteine conjugates, are bioactivated by renal cysteine conjugate beta-lyase to yield cytotoxic or mutagenic metabolites.4. Finally, hepatic glutathione conjugate formation with hydroquinones and aminophenols yields conjugates that are directed to gamma-glutamyltransferase-rich tissues, such as the kidney, where they undergo alkylation or redox cycling reactions, or both, that cause organ-selective damage.