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氨基甲酸酯类的致癌作用及其与DNA的结合

Carcinogenesis by carbamic acid esters and their binding to DNA.

作者信息

Pound A W, Lawson T A

出版信息

Cancer Res. 1976 Mar;36(3):1101-7.

PMID:175952
Abstract

The tumor-initiating potency of three simple alkyl carbamates and mono-N-substituted ethyl carbamates was examined in Hall strain mice. The binding of 14C-labeled carbamates of DNA was measured in Crackenbush mice. Ethyl carbamate was the most potent carcinogen for the epidermis, liver, and lung, followed by its N-alkyl derivatives. Methyl carbamate was without effect but n-propyl and n-butyl were possible carcinogens. The ethyl esters bound to a greater extent to DNA in liver and skin than the methyl, n-propyl, and n-butyl esters and only this binding persisted. A preliminary application of croton oil increased the yield of skin tumors but not of liver or lung tumors. It also increased the binding of the alkyl carbamates to DNA in skin, the increase being greatest with ethyl carbamate. The binding persisted longer in treated than in non-croton oil-treated mice.

摘要

在霍尔品系小鼠中检测了三种简单氨基甲酸烷基酯和单-N-取代氨基甲酸乙酯的肿瘤起始能力。在克拉肯布什小鼠中测量了14C标记的氨基甲酸酯与DNA的结合情况。氨基甲酸乙酯是对表皮、肝脏和肺部最具致癌性的物质,其次是其N-烷基衍生物。氨基甲酸甲酯没有作用,但正丙基和正丁基可能是致癌物。与甲基、正丙基和正丁基酯相比,乙基酯在肝脏和皮肤中与DNA的结合程度更高,且只有这种结合持续存在。巴豆油的初步应用增加了皮肤肿瘤的发生率,但未增加肝脏或肺部肿瘤的发生率。它还增加了烷基氨基甲酸酯与皮肤中DNA的结合,氨基甲酸乙酯的增加最为显著。与未用巴豆油处理的小鼠相比,处理过的小鼠中这种结合持续的时间更长。

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