Khan S, Martin M, Rahimtula A D, Payne J F
Biochemistry Department, Memorial University of Newfoundland, St. John's, Canada.
Can J Physiol Pharmacol. 1987 Dec;65(12):2400-8. doi: 10.1139/y87-381.
Administration of a Prudhoe Bay crude oil (PBCO) to pregnant rats resulted in induction of hepatic microsomal P-450 levels and various monooxygenases in a dose-dependent manner. The activities of aniline hydroxylase, benzo[a]pyrene hydroxylase, aminopyrine-N-demethylase, ethoxyresorufin-O-deethylase, and pentoxyresorufin-O-depentylase were increased 2-3-fold, 12-15-fold, 1.4-1.8-fold, 20-24-fold, and 6-8-fold, respectively, on gestation day 18, when a single dose of PBCO (5-10 mL/kg body weight, p.o.) had been administered 24 h earlier. Glutathione-S-transferase, UDPG transferase, and DT-diaphorase activities were also increased; however, maximum induction was noticed when crude oil was given 72 h earlier. Repeated exposure (day 6-day 17, daily) of crude oil at lower levels was able to produce similar induction patterns in enzyme systems at day 18 of gestation. The xenobiotic-metabolizing enzyme systems were also induced transplacentally: treatment of pregnant rats with PBCO induced both placental and fetal hepatic enzyme systems. Liver microsomal P-450 contents, benzo[a]pyrene hydroxylase, and ethoxyresorufin-O-deethylase activities were increased 2-fold, 2-3-fold, and 10-12-fold, respectively in 18-day-old fetuses. Similar trends were noticed in placenta. Activities of phase II enzymes such as glutathione-S-transferase, UDPG transferase, and DT-diaphorase were also significantly elevated. It is suggested that crude oil induces maternal hepatic drug metabolism and that some of its constituents (mainly aromatic hydrocarbons) and (or) their metabolites pass through the placenta and thus induce drug-metabolizing enzymes transplacentally. The practical importance of the results in relation to human and environmental health is also discussed.
给怀孕大鼠施用普拉德霍湾原油（PBCO）会导致肝微粒体P - 450水平和各种单加氧酶呈剂量依赖性诱导。在妊娠第18天，当24小时前单次口服给予PBCO（5 - 10 mL/kg体重）时，苯胺羟化酶、苯并[a]芘羟化酶、氨基比林 - N - 脱甲基酶、乙氧异羟肟酸 - O - 脱乙基酶和戊氧异羟肟酸 - O - 脱戊基酶的活性分别增加了2 - 3倍、12 - 15倍、1.4 - 1.8倍、20 - 24倍和6 - 8倍。谷胱甘肽 - S - 转移酶、UDPG转移酶和DT - 黄递酶的活性也增加；然而，当提前72小时给予原油时，观察到最大诱导作用。在妊娠第6天至第17天每天重复低水平暴露原油，能够在妊娠第18天的酶系统中产生类似的诱导模式。外源性物质代谢酶系统也通过胎盘诱导：用PBCO处理怀孕大鼠会诱导胎盘和胎儿肝脏酶系统。在18日龄胎儿中，肝微粒体P - 450含量、苯并[a]芘羟化酶和乙氧异羟肟酸 - O - 脱乙基酶活性分别增加了2倍、2 - 3倍和10 - 12倍。在胎盘中也观察到类似趋势。谷胱甘肽 - S - 转移酶、UDPG转移酶和DT - 黄递酶等II相酶的活性也显著升高。提示原油诱导母体肝脏药物代谢，其某些成分（主要是芳烃）和（或）其代谢产物穿过胎盘，从而经胎盘诱导药物代谢酶。还讨论了这些结果对人类和环境健康的实际重要性。
