Walker Stormy A, Whitten Linwood B, Seals George B, Lee Whitney E, Archibong Anthony E, Ramesh Aramandla
Department of Pharmacology, Meharry Medical College, Nashville, TN 37208, USA.
Food Chem Toxicol. 2006 Mar;44(3):380-7. doi: 10.1016/j.fct.2005.08.010. Epub 2005 Sep 22.
The magnitude of susceptibility to toxicant exposure may depend on the ability of animals to metabolize the chemicals. The present study has been undertaken to see whether any differences exist among mammals in the metabolism of fluoranthene (FLA), a polycyclic aromatic hydrocarbon (PAH) compound. Microsomes were isolated from the small intestine and liver of rat, mouse, hamster, goat, sheep, pig, dog, cow, monkey, and humans (commercially procured), and incubated with FLA. Post-incubation, samples were extracted with ethyl acetate and analyzed for FLA/metabolites by reverse-phase HPLC with fluorescence detection. The metabolism of FLA in both liver and small intestine was in the order: human > monkey > cow > goat > sheep > dog > pig > hamster > rat > mouse under conditions of the test system used. The rate of metabolism (pmol of metabolite/min/mg protein) was found to be more in liver than in intestine in all the species studied. The FLA metabolites identified were FLA 2,3-diol, trans-2,3-dihydroxy-1,10b-epoxy-1,2,3,10beta tetrahydro FLA (2,3D FLA), 3-hydroxy FLA, and 8-hydroxy FLA. The rodent microsomes produced considerably higher proportion of FLA 2,3-diol, and 2,3D FLA than did pig, dog, and humans. On the other hand, microsomes from higher mammals converted a greater proportion of FLA to 3-hydroxy FLA, the detoxification product of FLA. Overall, our results revealed a great variation among species to metabolize FLA.
对毒物暴露的易感性程度可能取决于动物代谢化学物质的能力。本研究旨在探究哺乳动物在多环芳烃(PAH)化合物荧蒽(FLA)代谢方面是否存在差异。从大鼠、小鼠、仓鼠、山羊、绵羊、猪、狗、牛、猴子和人类(商业采购)的小肠和肝脏中分离出微粒体,并与FLA一起孵育。孵育后,用乙酸乙酯提取样品,并通过带有荧光检测的反相高效液相色谱法分析FLA/代谢物。在所使用的测试系统条件下,肝脏和小肠中FLA的代谢顺序为:人类>猴子>牛>山羊>绵羊>狗>猪>仓鼠>大鼠>小鼠。在所有研究的物种中,发现肝脏中的代谢速率(代谢物的皮摩尔数/分钟/毫克蛋白质)比小肠中的更高。鉴定出的FLA代谢物有FLA 2,3 -二醇、反式 - 2,3 -二羟基 - 1,10b -环氧 - 1,2,3,10β -四氢FLA(2,3D FLA)、3 -羟基FLA和8 -羟基FLA。啮齿动物的微粒体产生的FLA 2,3 -二醇和2,3D FLA的比例比猪、狗和人类的高得多。另一方面,来自高等哺乳动物的微粒体将更大比例的FLA转化为3 -羟基FLA,即FLA的解毒产物。总体而言,我们的结果揭示了不同物种在代谢FLA方面存在很大差异。