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微粒体在体外将4-二甲基氨基偶氮苯和氨基甲酸乙酯形成器官特异性最终致癌物。

In vitro formation of organ-specific ultimate carcinogens of 4-dimethylaminoazobenzene and urethan by microsomes.

作者信息

Gupta R, Dani H M

机构信息

Department of Biochemistry, Panjab University, Chandigarh, India.

出版信息

Toxicol Lett. 1989 Jan;45(1):49-54. doi: 10.1016/0378-4274(89)90158-6.

DOI:10.1016/0378-4274(89)90158-6
PMID:2492687
Abstract

In order to determine the organ-specific carcinogenicity of 4-dimethylaminoazobenzene (4-DAB) and urethan, their metabolites formed in vitro by incubation with the microsomes from liver, lungs, brain and kidneys of rats were isolated by thin-layer chromatography. 4-DAB was found to be metabolized to give two major products, 4-aminoazobenzene and N-hydroxy-4-aminoazobenzene, only when incubated with liver microsomes. These metabolites were not detected when microsomal suspensions of lungs, brain and kidneys were used. Similarly, urethan was found to yield three metabolites, N-hydroxy derivative of ethyl carbamate, N-hydroxyvinyl carbamate, and epoxy derivative of ethyl carbamate, on incubation with lung microsomes, but not with the microsomes from liver, brain and kidneys. As the potential carcinogenic moieties were only formed by incubating these two compounds with the microsomes of their target organs, their organ-specific carcinogenicity may be explained.

摘要

为了确定4-二甲基氨基偶氮苯(4-DAB)和氨基甲酸乙酯的器官特异性致癌性,通过薄层色谱法分离了它们与大鼠肝脏、肺、脑和肾脏微粒体体外孵育形成的代谢产物。结果发现,只有在与肝脏微粒体孵育时,4-DAB才会代谢产生两种主要产物,即4-氨基偶氮苯和N-羟基-4-氨基偶氮苯。当使用肺、脑和肾脏的微粒体悬浮液时,未检测到这些代谢产物。同样,发现氨基甲酸乙酯与肺微粒体孵育时会产生三种代谢产物,即氨基甲酸乙酯的N-羟基衍生物、N-羟基乙烯基氨基甲酸酯和氨基甲酸乙酯的环氧衍生物,但与肝脏、脑和肾脏的微粒体孵育时则不会产生。由于只有将这两种化合物与它们靶器官的微粒体孵育时才会形成潜在的致癌部分,因此可以解释它们的器官特异性致癌性。

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