遗传毒性:对DNA的损害及其后果。

EXS Pub Date : 2009-01-01 DOI:10.1007/978-3-7643-8336-7_4
David H Phillips, Volker M Arlt
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引用次数: 106

摘要

基因毒素是一种能导致DNA或染色体损伤的化学物质或制剂。生殖细胞的这种损伤有可能导致遗传性状的改变(种系突变)。体细胞的DNA损伤可能导致体细胞突变,而体细胞突变可能导致恶性转化(癌症)。已经开发了许多体外和体内遗传毒性试验,这些试验具有一系列终点,可检测原核生物(如细菌)或真核生物(如哺乳动物、鸟类或酵母)细胞中的DNA损伤或其生物学后果。这些试验用于评估环境化学品和消费品的安全性,并探索已知或可疑致癌物的作用机制。许多化学致癌物/诱变剂经过代谢激活成为与DNA共价结合的活性物质,因此形成的DNA加合物可以通过各种敏感技术在细胞和人体组织中检测到。人体组织中DNA加合物的检测和表征为人类癌症的病因学提供了线索。人类肿瘤中基因突变的特征,与实验系统中已知的基因毒素致突变谱一样,可能会进一步深入了解环境诱变剂在人类癌症中的作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Genotoxicity: damage to DNA and its consequences.

A genotoxin is a chemical or agent that can cause DNA or chromosomal damage. Such damage in a germ cell has the potential to cause a heritable altered trait (germline mutation). DNA damage in a somatic cell may result in a somatic mutation, which may lead to malignant transformation (cancer). Many in vitro and in vivo tests for genotoxicity have been developed that, with a range of endpoints, detect DNA damage or its biological consequences in prokaryotic (e.g. bacterial) or eukaryotic (e.g. mammalian, avian or yeast) cells. These assays are used to evaluate the safety of environmental chemicals and consumer products and to explore the mechanism of action of known or suspected carcinogens. Many chemical carcinogens/mutagens undergo metabolic activation to reactive species that bind covalently to DNA, and the DNA adducts thus formed can be detected in cells and in human tissues by a variety of sensitive techniques. The detection and characterisation of DNA adducts in human tissues provides clues to the aetiology of human cancer. Characterisation of gene mutations in human tumours, in common with the known mutagenic profiles of genotoxins in experimental systems, may provide further insight into the role of environmental mutagens in human cancer.

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