EFFECTS OF ENVIRONMENTAL CHEMICALS ON DRUG-METABOLIZING ENZYMES

环境化学品对药物代谢酶的影响

• 批准号: 4693155
• 负责人: J A GOLDSTEIN
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/4693155
• 关键词: acetylaminofluorene; aging; antibody formation; complementary DNA; cytochrome P450; detoxification; dioxins; environmental toxicology; enzyme induction /repression; genetic manipulation; genetic regulation; genetic translation; halobiphenyl /halotriphenyl compound; isozymes; liver metabolism; messenger RNA; microsomes; molecular cloning; toxin metabolism

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.

本研究的目的是检查亚种的变化， 环境污染物处理后大鼠细胞色素P-450 c和P-450 d的变化 化学品，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过程 表明3，4，5，3 ′，4 ′，5 ′-HCB协同诱导P-450 d。 2.用作自杀底物的亚甲二氧基苯基化合物（MDO） 诱导不同P-450同工酶。 它们的形成能力也不同 不同同工酶的复合物。 甲基胆蒽联合给药 在mRNA水平上抑制MDO对P-450 b的诱导作用。 3.氯苯类化合物作为诱导剂的构效关系 研究了 六氯苯是唯一的3-MC型诱导剂。 4.已分离出两种组成型同工酶P-450 H和P-450 G， 这些形式的抗体。 本项目的目标是更好地了解 暴露后肝脏对化学物质的代谢能力 环境化学品。 针对这些基因开发的抗体和cDNA 细胞色素将用于研究这些影响。