N-亚硝基-2-甲氧基-2,6-二甲基吗啉在仓鼠体内的代谢与致突变性

Metabolism and mutagenicity of N-nitroso-2-methoxy-2,6-dimethylmorpholine in hamsters.

作者信息

Gingell R, Brunk G, Nagel D, Wallcave L, Walker B, Pour P

出版信息

J Natl Cancer Inst. 1980 Jan;64(1):157-61.

Abstract

N-Nitroso-2-methoxy-2,6-dimethylmorpholine (MeNDMM) was derived from the cyclic form of N-nitroso-(2-hydroxypropyl)(2-oxopropyl)amine (HPOP), a proposed proximate pancreatic carcinogen for the hamster. MeNDMM was metabolized in vivo by noninbred Syrian golden hamsters to HPOP, which was excreted in urine. In vitro metabolism produced HPOP by cytochrome P450-mediated oxidative demethylation. MeNDMM and HPOP were similarly mutagenic in the Ames Salmonella typhimurium assay, in which hamster liver preparations were used for metabolic activation. MeNDMM, due to its metabolism to HPOP, is probably also a pancreatic carcinogen in the hamster.

摘要

N-亚硝基-2-甲氧基-2,6-二甲基吗啉（MeNDMM）源自N-亚硝基-（2-羟丙基）（2-氧代丙基）胺（HPOP）的环状形式，HPOP是一种推测的仓鼠胰腺近端致癌物。非近交系叙利亚金仓鼠在体内将MeNDMM代谢为HPOP，HPOP通过尿液排出。体外代谢通过细胞色素P450介导的氧化脱甲基作用产生HPOP。在使用仓鼠肝脏制剂进行代谢活化的鼠伤寒沙门氏菌Ames试验中，MeNDMM和HPOP具有相似的致突变性。由于MeNDMM可代谢为HPOP，它可能也是仓鼠的胰腺致癌物。

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