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新合成的抗肿瘤药物氨脒腙、双吖啶和三甲双吖啶的遗传毒性特性。

Genotoxic properties of the newly synthesized antineoplastic agents amidox, didox and trimidox.

作者信息

Miadoková E, Macáková K, Podstavková S, Vlcek D

机构信息

Department of Genetics, Faculty of Sciences, Bratislava, Slovakia.

出版信息

Pharmazie. 1997 Jul;52(7):540-4.

PMID:9266591
Abstract

Toxic and genotoxic effects of three polyhydroxy-substituted benzohydroxamates (amidox, didox and trimidox), having antineoplastic activities by the mechanism of the ribonucleotid reductase activity inhibition, were evaluated by reverse mutation assay on Salmonella typhimurium strains TA97, TA98, TA100, TA102. While amidox did not exhert any toxic effect, didox and trimidox were toxic. The toxicity of the test chemicals was dependent on the structure of their molecule and the repair capacity of the test strains. Trimidox exhibited the highest toxicity, and it was proved as a direct-acting frameshift mutagen. Its mutagenic effect was increased after a metabolic activation. Amidox and didox can be classified as frameshift promutagens.

摘要

通过对鼠伤寒沙门氏菌TA97、TA98、TA100、TA102菌株进行回复突变试验,评估了三种具有抗肿瘤活性(通过抑制核糖核苷酸还原酶活性的机制)的多羟基取代苯甲酰异羟肟酸酯(氨甲肟、双羟肟酸和三甲肟)的毒性和遗传毒性。虽然氨甲肟没有表现出任何毒性,但双羟肟酸和三甲肟具有毒性。受试化学品的毒性取决于其分子结构和受试菌株的修复能力。三甲肟表现出最高的毒性,并且被证明是一种直接作用的移码诱变剂。经过代谢活化后,其诱变作用增强。氨甲肟和双羟肟酸可归类为移码前诱变剂。

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