鸭肝微粒体对苯并(a)芘的代谢

Sangeet Honey , Patrick O’Keefe , Adam T. Drahushuk , James R. Olson , Subodh Kumar , Harish C. Sikka
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引用次数: 17

摘要

研究了从化学污染地区和相对非污染地区采集的绿头鸭(Anas platyrhynchos)和秋沙鸭(Mergus merganser americanus)两种鸭的肝脏微粒体对典型致癌性多环芳烃苯并(a)芘(BP)的代谢。污染地区沙鸭和绿头鸭肝脏微粒体对BP的代谢率(分别为2650±310和2200±310 pmol/min / mg微粒体蛋白)显著高于非污染地区沙鸭和绿头鸭肝脏微粒体对BP的代谢率(分别为334±33和231±30 pmol/min / mg微粒体蛋白)。污染地区鸭肝微粒体细胞色素P-450 - 1A1水平显著高于非污染地区鸭。污染地区和非污染地区鸭肝微粒体中BP的主要代谢产物BP-9、10-二醇、BP-4、5-二醇、BP-7、8-二醇、BP-1、6-二酮、BP-3、6-二酮、BP-6、12-二酮、9-羟基BP和3-羟基BP的质量相似。然而,这些代谢物的模式彼此有很大的不同。来自污染地区的鸭肝微粒体产生的苯并环二氢二醇的比例高于来自非污染地区的鸭肝微粒体,后者将BP转化为BP-酚的比例更高。两种鸭肝微粒体形成的bp -7,8-二醇的优势对映体具有(−)R,R绝对立体化学。结果表明,鸭和大鼠肝微粒体酶在BP代谢中具有不同的区域选择性,但具有相似的立体选择性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Metabolism of benzo(a)pyrene by duck liver microsomes

The metabolism of benzo(a)pyrene [BP], a model carcinogenic PAH, by hepatic microsomes of two duck species, mallard (Anas platyrhynchos) and common merganser (Mergus merganser americanus) collected from chemically-contaminated and relatively non-contaminated areas was investigated. The rate of metabolism of BP by liver microsomes of common merganser and mallard collected from polluted areas (2650±310 and 2200±310 pmol/min per mg microsomal protein, respectively) was significantly higher than that obtained with liver microsomes of the two species collected from non-polluted areas (334±33 and 231±30 pmol/min per mg microsomal protein, respectively). The level of cytochrome P-450 1A1 was significantly higher in the liver microsomes of both duck species from the polluted areas as compared to the ducks from the non-polluted areas. The major BP metabolites, including BP-9, 10-diol, BP-4, 5-diol, BP-7, 8-diol, BP-1, 6-dione, BP-3, 6-dione, BP-6, 12-dione, 9-hydroxy-BP and 3-hydroxy-BP, formed by liver microsomes of both duck species from polluted and non-polluted areas, were qualitatively similar. However, the patterns of these metabolites were considerably different from each other. Liver microsomes of ducks from the polluted areas produced a higher proportion of benzo-ring dihydrodiols than the liver microsomes of ducks from the non-polluted areas, which converted a greater proportion of BP to BP-phenols. The predominant enantiomer of BP-7,8-diol formed by hepatic microsomes of the two duck species had an (−)R,R absolute stereochemistry. The data suggest that duck and rat liver microsomal enzymes have different regioselectivity but similar stereoselectivity in the metabolism of BP.

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