Lucier G W, McDaniel O S
Ann N Y Acad Sci. 1979 May 31;320:449-57. doi: 10.1111/j.1749-6632.1979.tb56626.x.
Our studies were designed to define structure-activity relationships for the effects of pure PCB congeners and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on hepatic enzyme development. The organohalogens were usually administered to pregnant rats and enzyme activities measured in fetuses and offspring (6, 20, and 55 days after birth). Offspring of pregnant rats exposed to TCDD had elevated levels of benzpyrene hydroxylase and nonsteroid UDP glucuronyltransferase (UDPGT). Postnatal inductive actions of TCDD were caused primarily by newborn exposure to TCDD in milk. 3,4-3',4'-Tetrachlorobiphenyl (4-CB) induced P448-dependent enzymes in 6- and 20 day-old rats whereas 2,4,5-2',4',5'-hexachlorobiphenyl (6-CB) induced P450-dependent enzymes. 4-CB was a potent teratogen (behavioral and kidney abnormalities) but 6-CB produced no such developmental defects. 4-CB might also alter the normal imprinting of sexual differentiation of hepatic metabolism as evidenced by a feminization (decrease) of UDPGT in adult male rats which were exposed neonatally to 4-CB. Therefore, the organohalogens might alter the ontogeny of hepatic metabolism in two ways: induction and imprinting.
我们的研究旨在确定纯多氯联苯同系物和2,3,7,8-四氯二苯并对二恶英（TCDD）对肝脏酶发育影响的构效关系。通常给怀孕大鼠施用有机卤化物，并测量胎儿和后代（出生后6天、20天和55天）的酶活性。暴露于TCDD的怀孕大鼠的后代中，苯并芘羟化酶和非甾体UDP葡萄糖醛酸基转移酶（UDPGT）水平升高。TCDD的产后诱导作用主要是由于新生动物通过乳汁接触TCDD所致。3,4-3',4'-四氯联苯（4-CB）在6日龄和20日龄大鼠中诱导P448依赖性酶，而2,4,5-2',4',5'-六氯联苯（6-CB）诱导P450依赖性酶。4-CB是一种强效致畸剂（行为和肾脏异常），但6-CB不会产生此类发育缺陷。4-CB还可能改变肝脏代谢性别分化的正常印记，这在新生期暴露于4-CB的成年雄性大鼠中UDPGT的女性化（降低）中得到了证明。因此，有机卤化物可能通过两种方式改变肝脏代谢的个体发生：诱导和印记。
