EFFECTS OF ENVIRONMENTAL CHEMICALS ON DRUG-METABOLIZING ENZYMES

这些研究的目的是研究六岁，年龄， 菌株和环境化学品对细胞色素P-450酶及相关酶影响 肝脏代谢类固醇的能力的这些变化， 异物。 1.细胞色素P-450 g在远交CD大鼠中高度可变（高和低 种群）和缺席费舍尔大鼠。 它是男性特有的， 只有在青春期之后。 这种酶代谢类固醇，但没有 类固醇羟基化在高和低之间的显著差异 CD大鼠的表型。 2.细胞色素P-450 UT-H（异喹胍形式）和细胞色素P-450 2c（a 雄性特异性同工酶）被有毒的PCB异构体降低（40%和90%）， 而3-MC和苯巴比妥的作用程度较低。 代谢 通过肝微粒体（P-4502 c介导）在2和16- 职位也大幅减少。 减少 睾酮的6 β-羟基化和7 α-羟基化的增加 也发生，并可能参与内分泌状态的变化， 多氯联苯暴露大鼠。 3.六氯苯与Ah受体的可能结合及其机制 研究了P1-450和P3-450的诱导。 的一些证据 该研究表明，Ah基因座参与了六氯苯的作用。 这个项目的目标是更好地了解能力的变化， 肝脏代谢激素和外来化学物质后暴露于 环境化学品。

The objectives of these studies were to study the effects of six, age, strain, and environmental chemicals on cytochrome P-450 enzymes and relate these changes to the ability of the liver to metabolize steroids and foreign compounds. 1. Cytochrome P-450g is highly variable in outbred CD rats (high and low populations) and absent in the Fischer rat. It is male specific and found only after puberty. This enzyme metabolizes steroids but there were no significant differences in steroid hydroxylation between high and low phenotypes of CD rats. 2. Cytochrome P-450 UT-H (debrisoquine form) and cytochrome P-450 2c (a male specific isozyme) were decreased (40% and 90%) by a toxic PCB isomer, and to a lesser extent by 3-MC and phenobarbital. Metabolism of testosterone by liver microsomes (P-4502c mediated) at the 2- and 16- positions was also decreased dramatically. Decreases in 6Beta-hydroxylation of testosterone and increases in 7Alpha-hydroxylation also occurred, and may be involved in changes in endocrine status of the PCB exposed rat. 3. The possible binding of hexachlorobenzene to the Ah receptor and its induction of P1-450 and P3-450 is being investigated. Some evidence for involvement of the Ah locus in the action of hexachlorobenzene is indicated. The goal of this project is to better understand changes in the ability of the liver to metabolize hormones and foreign chemicals after exposure to environmental chemicals.