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NADH 依赖的微粒体激活二甲基亚硝胺后沙门氏菌中的诱变作用。

Mutagenesis in Salmonella after NADH-dependent microsomal activation of dimethylnitrosamine.

作者信息

Fong L Y, Lee K M, Lin H J

出版信息

Mutat Res. 1982 Aug;105(1-2):29-36. doi: 10.1016/0165-7992(82)90204-4.

DOI:10.1016/0165-7992(82)90204-4
PMID:6750374
Abstract

The mutagenic activity of dimethylnitrosamine activated by rat-liver microsomes in the presence of NADH was compared with that obtained with NADPH. 3 histidine auxotrophic strains of Salmonella underwent reversions after activation with NADH as the sole coenzyme. All 3 tester strains showed a dose-response relationship with dimethylnitrosamine (10-125 mumoles per plate) after NADH-supported activation. With NADH as the sole coenzyme, the most sensitive strain, hisG46, showed a 105-fold increase in mutagenesis frequency as compared with the 230-fold increase obtained with NADPH. Activation of dimethylnitrosamine in the presence of NADH and NADPH, in combination, produced mutagenesis at frequencies above those seen with NADH alone, but less than or equal to those seen with NADPH as the only coenzyme during the activation step. Experiments in vitro showed that microsomal incorporation of carbon from [14C]dimethylnitrosamine was highest in the presence of NADPH, lowest with NADH and reached intermediate levels when both coenzymes were present. The source of the microsomes in all experiments was liver from rats pre-treated with Aroclor 1254.

摘要

将大鼠肝脏微粒体在NADH存在下激活的二甲基亚硝胺的诱变活性与用NADPH获得的诱变活性进行了比较。3种组氨酸营养缺陷型沙门氏菌菌株在用NADH作为唯一辅酶激活后发生了回复突变。在NADH支持的激活后,所有3种测试菌株都与二甲基亚硝胺(每平板10 - 125微摩尔)呈现剂量反应关系。以NADH作为唯一辅酶时,最敏感的菌株hisG46的诱变频率比用NADPH时增加230倍的情况增加了105倍。在NADH和NADPH共同存在下激活二甲基亚硝胺,产生的诱变频率高于单独使用NADH时,但小于或等于在激活步骤中仅使用NADPH作为辅酶时所观察到的频率。体外实验表明,[14C]二甲基亚硝胺的碳在微粒体中的掺入量在NADPH存在时最高,在NADH存在时最低,当两种辅酶都存在时达到中间水平。所有实验中微粒体的来源都是用多氯联苯1254预处理过的大鼠的肝脏。

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