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苯并(a)芘暴露对小鼠脂肪组织微粒体代谢荧蒽的影响。

Effect of benzo(a)pyrene exposure on fluoranthene metabolism by mouse adipose tissue microsomes.

机构信息

Department of Biochemistry & Cancer Biology, Meharry Medical College, 1005 D.B. Todd Blvd., Nashville, TN 37208, USA.

出版信息

Toxicol Mech Methods. 2010 Feb;20(2):53-8. doi: 10.3109/15376510903584677.

Abstract

The present study has been undertaken to examine whether exposure to benzo(a)pyrene (BaP), a polycyclic aromatic hydrocarbon (PAH) compound, influences the metabolism of fluoranthene (FLA), another PAH compound. Microsomes were isolated from the adipose tissue of mice that received 50 microg/kg BaP and incubated with FLA (3 microM) alone; FLA in combination with BaP at equimolar concentrations, and a control group that received nothing. Post-incubation, samples were extracted with ethyl acetate and analyzed for FLA metabolites by reverse-phase HPLC with fluorescence detection. The rate of FLA metabolism (pmol of metabolite/min/mg protein) was increased when microsomes from BaP-treated mice were exposed to FLA alone and FLA in combination with BaP, compared to controls. On the other hand, the difference in FLA metabolic rate between microsomes that were exposed to FLA + BaP was higher than the ones that received FLA. The microsomes from BaP-pre-treated mice produced a considerably higher proportion of FLA 2, 3-diol, and 2, 3 D FLA when microsomes were incubated with FLA. There were no differences in the FLA metabolite types formed when BaP-pre-treated mice were co-incubated with BaP and FLA than with FLA alone. The enhanced biotransformation of FLA as a result of prior and concomitant exposure to BaP may have implications for assessment of risks arising from human exposure to PAH mixtures.

摘要

本研究旨在探讨多环芳烃(PAH)化合物苯并(a)芘(BaP)暴露是否会影响另一种 PAH 化合物荧蒽(FLA)的代谢。从小鼠的脂肪组织中分离出微粒体,这些小鼠接受了 50μg/kg 的 BaP 并单独用 FLA(3μM)孵育;FLA 与 BaP 以等摩尔浓度联合孵育;对照组则未接受任何处理。孵育后,用乙酸乙酯提取样品,并通过反相 HPLC 与荧光检测分析 FLA 代谢物。与对照组相比,当 BaP 处理的小鼠的微粒体单独暴露于 FLA 或 FLA 与 BaP 联合暴露时,FLA 的代谢率(每分钟每毫克蛋白代谢物的 pmol)增加。另一方面,暴露于 FLA + BaP 的微粒体之间的 FLA 代谢率差异高于接受 FLA 的微粒体。当用 FLA 孵育时,经 BaP 预处理的小鼠的微粒体产生了相当高比例的 FLA 2,3-二醇和 2,3 D FLA。当 BaP 预处理的小鼠与 BaP 和 FLA 共孵育时,与单独用 FLA 孵育相比,形成的 FLA 代谢物类型没有差异。由于先前和同时暴露于 BaP,FLA 的生物转化增强可能会对评估人类暴露于 PAH 混合物所带来的风险产生影响。

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