EFFECTS OF ENVIRONMENTAL CHEMICALS ON DRUG-METABOLIZING ENZYMES

这些研究的目的是研究六岁、年龄、 菌株和环境化学物质对细胞色素P-450酶的影响及相关 肝脏代谢类固醇和类固醇能力的这些变化 外国化合物。 1.细胞色素P-450G在近交系CD大鼠(高、低)中高度变异 种群)，在Fischer大鼠中不存在。它是男性特有的，并发现了 只有在青春期之后。这种酶代谢类固醇，但没有 高、低水平人群类固醇羟化水平差异显著 CD大鼠的表型。 2.细胞色素P-450 UT-H(脱氢异喹)和细胞色素P-450 2c(a 雄性特有同工酶)被有毒的多氯联苯异构体降低(40%和90%)， 3-MC和苯巴比妥的作用较小。新陈代谢 肝微体(P-4502c介导)2位和16位的睾酮 仓位也大幅减少。减少了 6睾酮β-羟化和7α-羟化增加 也会发生，并可能参与内分泌状态的变化 多氯联苯暴露大鼠。 3.六氯苯可能与AH受体及其受体结合 对P1-450和P3-450的诱导作用正在研究中。一些证据表明 结果表明，Ah基因参与了六氯苯的作用。 该项目的目标是更好地了解 暴露后肝脏代谢激素和外来化学物质 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.