摘要
呼吸道是人体暴露于有毒外源化学物的主要途径之一。肺组织存在多种生物酶类如细胞色素P450、前列腺素H合酶、脂氧合酶和谷胱甘肽-S-转移酶等,可对吸入的化学物进行代谢活化或解毒,产生相应的生物学效应,引起机体的结构和功能改变,产生毒性作用。本文从以下几个方面进行综述:(1)黄曲霉毒素B1在肺内代谢为黄曲霉毒素B1-8,9-环氧化物;(2)碳链化合物在各酶类作用下生成的环氧化物、氢氧化物、重氮化物等活性中间产物;(3)芳香族化合物在肺内代谢为醌类、环氧化物和酯类等活性物质;(4)无机化合物在肺内甲基转移酶和还原剂的作用下生成甲基化代谢物及金属离子;此外,还对这些活性中间产物或终致癌物对肺产生的细胞毒性和基因毒性进行总结,以阐明外源化学物在肺内原位代谢与其致癌、致畸和致突变机制的关系。
Inhalation is one of the main routes of human exposure to hazardous exogenous chemicals.These exogenous chemicals can be activated or detoxicated by various enzymes existing in the lungs,such as cytochrome P450, prostaglandin H synthase, lipoxygenase and glutathione S-transferase, to generate corresponding biological effects,lead to structural and functional changes, and result in toxic effects. In order to elucidate the relationship between the in situ metabolism of exogenous chemicals in the lungs and their carcinogenic, teratogenic and mutagenic mechanisms, this article summarizes the latest research progress from four perspectives：（1） aflatoxin B1 is metabolized to aflatoxin B1-8, 9-epoxide in the lungs;（2）carbon chain compounds are metabolized by enzymes into reactive intermediates such as epoxides, hydroxides, and diazocompounds;（3） aromatic compounds are metabolized into reactive intermediates such asquinones, epoxides and esters in the lungs;（4） inorganic compounds generate methylated metabolites and metal ions under the metabolism of methyltransferases and reducing agents in the lungs; as well as the cytotoxicity and genotoxicity of these reactive intermediates or final carcinogens to the lungs.
作者
邓利红
胡建安
DENG Li-hong;HU Jian-an(Xiangya School of Public Health,Central South University,Changsha 410078,China)
出处
《中国药理学与毒理学杂志》
CAS
CSCD
北大核心
2018年第5期415-426,共12页
Chinese Journal of Pharmacology and Toxicology
基金
国家自然科学基金(81372966)~~
关键词
外源化学物
原位代谢
代谢酶
细胞色素P450
毒作用
exogenous chemicals
in situ metabolism
metabolic enzymes
cytochrome P450
toxic action
