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未诱导大鼠的S9和肝细胞将致癌性N-亚硝胺转化为诱变剂的代谢激活能力。

Metabolic activation capabilities of S9 and hepatocytes from uninduced rats to convert carcinogenic N-nitrosamines to mutagens.

作者信息

Rumruen K, Pool B L

出版信息

Mutat Res. 1984 Jun-Jul;140(2-3):147-53. doi: 10.1016/0165-7992(84)90060-5.

DOI:10.1016/0165-7992(84)90060-5
PMID:6379440
Abstract

6 carcinogenic nitrosamines were studied in Salmonella typhimurium TA1535 after activation by S9 and by hepatocytes. All nitrosamines were activated by S9 from induced rats, regardless of their organotropy. The hepatocarcinogenic nitrosamines (N-nitrosodimethylamine, NDMA; N-nitrosodiethylamine, NDEA; N-nitrosomorpholine, NM and N-nitrosodibutylamine, NDBA) were activated to mutagens by S9 and by hepatocytes both derived from noninduced rat livers, NDMA and NM inducing more his+ revertants in the presence of hepatocytes. The oesophageal carcinogenic nitrosamine N-nitrosomethylbenzylamine (NMBeA) and bladder organotrophic N-nitroso(4-hydroxybutyl)butylamine(NBBOH) were neither converted by liver preparations of uninduced rats into mutagenic intermediates nor by hepatocytes. This study indicates that isolated cells derived from untreated animals may be better suited to study liver specific activation in vitro than disrupted subcellular metabolizing systems from induced animals.

摘要

在经S9和肝细胞激活后,对鼠伤寒沙门氏菌TA1535中的6种致癌亚硝胺进行了研究。所有亚硝胺均可被诱导大鼠的S9激活,无论其器官亲和性如何。致癌性亚硝胺(N-亚硝基二甲胺,NDMA;N-亚硝基二乙胺,NDEA;N-亚硝基吗啉,NM和N-亚硝基二丁胺,NDBA)可被来自未诱导大鼠肝脏的S9和肝细胞激活为诱变剂,在肝细胞存在的情况下,NDMA和NM诱导出更多的组氨酸+回复突变体。致癌性亚硝胺N-亚硝基甲基苄胺(NMBeA)和膀胱亲和性N-亚硝基(4-羟基丁基)丁胺(NBBOH)既不能被未诱导大鼠的肝脏制剂转化为诱变中间体,也不能被肝细胞转化。这项研究表明,从未经处理的动物分离得到的细胞可能比来自诱导动物的破碎亚细胞代谢系统更适合用于体外研究肝脏特异性激活。

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