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短期遗传毒性试验的价值与局限性以及当前癌症生物测定化学物质选择标准的不足之处。

The value and limitations of short-term genotoxicity assays and the inadequacy of current criteria for selecting chemicals for cancer bioassays.

作者信息

Ashby J

出版信息

Food Chem Toxicol. 1986 Jun-Jul;24(6-7):663-6. doi: 10.1016/0278-6915(86)90154-7.

DOI:10.1016/0278-6915(86)90154-7
PMID:3781421
Abstract

The Salmonella gene mutation assay is established as the primary in vitro test for genotoxicity. It does not, however, detect all known genotoxic carcinogens, and several mammalian cell genotoxicity assays are now used to complement the Salmonella test--the most usual being cytogenetic analysis in vitro. Use of these two tests provides an adequate screen for genotoxins, but leaves undetected a variety of weak, DNA-unreactive animal carcinogens such as DDT, saccharin and diethylhexyl phthalate. A reappraisal of the present confused situation examines the underlying problems and options for action. It is suggested that the most effective way of focussing resources on the detection of possible new human carcinogens involves in vitro evaluation of genotoxicity, followed where appropriate by further evaluation in vivo, with urgent attention being paid to the methods currently used to select chemicals for cancer bioassays and to the resolution of the current debate on the validity of some recent classifications of carcinogenicity.

摘要

沙门氏菌基因突变试验是公认的用于遗传毒性检测的主要体外试验。然而,它并不能检测出所有已知的遗传毒性致癌物,因此现在使用几种哺乳动物细胞遗传毒性试验来补充沙门氏菌试验——最常用的是体外细胞遗传学分析。这两种试验的使用为遗传毒素提供了充分的筛选,但仍无法检测出多种弱的、与DNA无反应性的动物致癌物,如滴滴涕、糖精和邻苯二甲酸二乙基己酯。对当前混乱局面的重新评估审视了潜在问题和行动方案。有人建议,将资源集中用于检测可能的新型人类致癌物的最有效方法是进行遗传毒性的体外评估,然后在适当情况下进行进一步的体内评估,同时要迫切关注目前用于选择化学物质进行癌症生物测定的方法,以及解决当前关于一些近期致癌性分类有效性的争论。

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