n -亚硝基化合物的致癌性和致突变性。

Molecular toxicology Pub Date : 1987-01-01
W Lijinsky
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引用次数: 0

摘要

比较了几种不同种类的n -亚硝基化合物对大鼠和仓鼠的致癌活性和对沙门氏菌的致突变活性。虽然大多数直接作用的n -亚硝基化合物和那些需要代谢激活的化合物在适当的激活下具有诱变性,并且似乎在体内使DNA烷基化,但也有例外。其中一些是不会致癌的诱变剂;还有一些是非致突变的致癌物。即使在致突变性致癌物中,致突变性和致癌性之间也没有定量的关系。这意味着直接作用的化合物和那些需要代谢激活。亚硝胺两种活性之间缺乏一致性是由于代谢激活过程的复杂性导致了近致癌物的形成。诱变试验的缺陷似乎是由于在用于激活的肝微粒体中缺乏必要的酶。在烷基链β碳上携带氧的亚硝胺不会被大鼠微粒体酶氧化,因此不会被大鼠肝微粒体转化为细菌诱变剂。细菌致突变性不是n -亚硝基化合物致癌活性或这些化合物诱发癌症的机制的指南。
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Carcinogenicity and mutagenicity of N-nitroso compounds.

The carcinogenic activities in rats and hamsters and the mutagenic activity in Salmonella of a number of N-nitroso compounds belonging to various classes have been compared. While most directly acting N-nitroso compounds and those requiring metabolic activation are mutagenic with appropriate activation and seem to alkylate DNA in vivo, there are exceptions. Some of these are mutagens that are not carcinogenic; others are carcinogens that are nonmutagenic. Even among the mutagenic carcinogens, there is no quantitative relationship between mutagenic and carcinogenic activities. This implies to directly acting compounds and to those requiring metabolic activation. The lack of congruence between the two activities among the nitrosamines is due to the complexity of the metabolic activating processes leading to formation of proximate carcinogens. The deficiencies in the mutagenesis assay appear to arise from a lack of the necessary enzymes in the liver microsomal fractions used for activation. Nitrosamines bearing oxygen on the beta carbon of an alkyl chain are not oxidized by rat microsomal enzymes and hence are not converted to bacterial mutagens by rat liver microsomes. Bacterial mutagenicity is not a guide to carcinogenic activity of N-nitroso compounds or to the mechanisms by which these compounds induce cancer.

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