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黄曲霉毒素B1体外代谢的物种比较

Species comparison of in vitro metabolism of aflatoxin B1.

作者信息

Roebuck B D, Wogan G N

出版信息

Cancer Res. 1977 Jun;37(6):1649-56.

PMID:404034
Abstract

The metabolism of [14C]aflatoxin B1 by 9000 X g supernatant fraction of livers of duck, rat, mouse, monkey, and humans was compared by incubating the compound and liver fractions in the presence of cofactors and air for 30 min. The incubation medium was extracted with chloroform, and the soluble metabolites were separated on thinlayer plates and quantified; radioactivity remaining in the aqueous phase was determined in order to quantify metabolism to water-soluble derivatives. Duck, monkey, and human livers were most active in total conversion, each metabolizing approximately 80% of available substrate in 30 min. Rat and mouse livers had lower activites, metabolizing 15 to 20%. Duck liver produced mainly (60%) chloroform-insoluble derivatives, but all other species produced larger quantities of chloroform-soluble than insoluble metabolites. Aflatoxin Q1 was the principle chloroform-soluble metabolite produced by monkey, human, and rat liver, whereas duck liver produced mainly aflatoxicol in that fraction. Aflatoxin P1 was produced by monkey, human, and mouse liver, but not by duck and rat. The chromatographic region containing M1 and B2alpha contained low levels of radioactivity in all species except human. No consistent pattern of metabolism emerged which could be correlated with species differences in response to aflatoxin B1 toxicity or carcinogenicity.

摘要

通过在辅因子和空气存在的条件下,将[14C]黄曲霉毒素B1与鸭、大鼠、小鼠、猴子和人类肝脏的9000×g上清液组分一起孵育30分钟,比较了它们对[14C]黄曲霉毒素B1的代谢情况。用氯仿萃取孵育培养基,将可溶性代谢产物在薄板上分离并进行定量;测定水相中剩余的放射性,以对生成水溶性衍生物的代谢情况进行定量。鸭、猴子和人类肝脏在总转化率方面最为活跃,每种肝脏在30分钟内可代谢约80%的可用底物。大鼠和小鼠肝脏的活性较低,代谢率为15%至20%。鸭肝主要产生(60%)氯仿不溶性衍生物,但所有其他物种产生的氯仿可溶性代谢产物比不溶性代谢产物更多。黄曲霉毒素Q1是猴子、人类和大鼠肝脏产生的主要氯仿可溶性代谢产物,而鸭肝在该组分中主要产生黄曲霉毒素醇。黄曲霉毒素P1由猴子、人类和小鼠肝脏产生,但鸭和大鼠肝脏不产生。除人类外,所有物种中含有M1和B2α的色谱区域放射性水平较低。没有出现与对黄曲霉毒素B1毒性或致癌性的物种差异相关的一致代谢模式。

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