EFFECTS OF ENVIRONMENTAL CHEMICALS ON DRUG-METABOLIZING ENZYMES

这项研究的目的是检查亚种的变化 环境因素对大鼠细胞色素P-450c和P-450d的影响 并评估这些变化的影响。 1.多氯联苯异构体的诱导：剂量反应曲线和时间进程 表明P-450D是由3，4，5，3‘，4’，5‘-六氯联苯协同诱导的。 2.用作自杀底物的亚甲二氧基苯基化合物(MDO) 诱导不同的P-450同工酶。它们的形成能力也不同 具有不同同工酶的复合体。甲基胆蒽联合给药 在mRNA水平上抑制MDOS对P-450B的诱导作用。 3.氯苯类化合物作为诱导剂的构效关系 学习。六氯苯是唯一的3-MC型诱导剂。 4.分离到P-450h和P-450g两种同工酶。 抗体产生这些形式的抗体。 该项目的目标是更好地了解 染毒后肝脏对化学物质的代谢能力 环境化学品。抗体和cDNA发展到这些 细胞色素将用于研究这些影响。

The objectives of this study are to examine changes in subspecies of cytochrome P-450c and P-450d in the rat after treatment with environmental chemicals and to assess the implications of these changes. 1. Induction by a PCB Isomer: Dose response curves and time courses indicate that P-450d are coordinately induced by 3,4,5,3',4',5'-HCB. 2. Methylenedioxyphenyl compounds (MDO) which act as suicide substrates induce different P-450 isozymes. They also differ in their ability to form complexes with different isozymes. Coadministration of methylcholanthrene with MDOs represses induction of P-450b by MDOs at the level of mRNA. 3. Structure-activity relationships of chlorobenzenes as inducers was studied. Hexachlorobenzene is the only 3-MC type inducer. 4. Two constitutive isozymes have been isolated P-450H and P-450G and antibodies raised to these forms. The goal of this project is to better understand the changes occurring in metabolic capability of the liver toward chemical after exposure to environmental chemicals. Antibodies and cDNAs developed to these cytochromes will be used in studying these effects.