Watkins J B, Klaassen C D
J Anim Sci. 1986 Sep;63(3):933-42. doi: 10.2527/jas1986.633933x.
Wildlife, domesticated animals and humans are exposed daily to myriad chemicals present in our environment. The risk posed by these chemicals to one species is often determined by extrapolation from data gathered from another species. Several extensive studies have examined the capability of the liver to biotransform xenobiotics in animals commonly used in toxicity testing and in livestock. The present paper is a compilation of these data into a single source to permit comprehensive examination of inter-species variation in rates of hepatic biotransformation. Several substrates were studied for each enzyme system, including cytochrome P-450-dependent monooxygenases, epoxide hydrolases, UDP-glucuronosyltransferases, N-acetyltransferases, glutathione S-transferases and sulfotransferases. The numerous differences in substrate specificity for an individual enzymatic pathway reflect the apparent multiplicity of these enzymes in all 11 species studied. Several hundred- to several thousand-fold differences between species in enzymatic activities for certain substrates under well-defined conditions emphasize the need for caution and the risk of error in extrapolation of xenobiotic metabolism from one species to another. In spite of these uncertainties, knowledge of the rate of biotransformation may help us predict the fate of new chemicals in various species.
野生动物、家畜和人类每天都暴露于我们环境中存在的无数化学物质。这些化学物质对一个物种构成的风险通常是通过从另一物种收集的数据进行推断来确定的。几项广泛的研究考察了肝脏对毒性测试常用动物和家畜体内异生物转化的能力。本文将这些数据汇编成一个单一来源,以便全面考察肝脏生物转化速率的种间差异。对每个酶系统研究了几种底物,包括细胞色素P-450依赖性单加氧酶、环氧化物水解酶、UDP-葡糖醛酸基转移酶、N-乙酰转移酶、谷胱甘肽S-转移酶和磺基转移酶。单个酶促途径底物特异性的众多差异反映了所研究的所有11个物种中这些酶的明显多样性。在明确界定的条件下,某些底物的酶活性在物种之间存在数百到数千倍的差异,这强调了在将异生物代谢从一个物种外推到另一个物种时需要谨慎以及存在错误风险。尽管存在这些不确定性,但生物转化速率的知识可能有助于我们预测新化学物质在各种物种中的命运。