毒理学相关资料,第一章内容参考文献7.pdfVIP

168 Chem. Res. Toxicol. 1991, 4 , 168-179 Role of Human Cytochrome P-450 I I E l in the Oxidation of Many Low Molecular Weight Cancer Suspects F. Peter Guengerich,* Dong-Hyun Kim,? and Masahiko Iwasaki* Department of Biochemistry and Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0146 Received October 5, 1990 The role of human cytochrome P-450 IIEl (P-450 IIE1) in the oxidation of a number of suspect carcinogens was examined by using a variety of approaches, including (1)selective inhibition of catalytic activity in human liver microsomes by diethyldithiocarbamate, which was found to be a selective mechanism-based inactivator of P-450 IIE1, (2) correlation of rates of different catalytic activities with each other and with chlorzoxazone 6-hydroxylation, an indicator of P-450 IIE1, in human liver microsomes, (3) demonstration of catalytic activity in reconstituted systems containing purified human P-450 IIE1, and (4) immunoinhibition of catalytic activity in human liver microsomes with rabbit anti-human P-450 IIE1. The results collectively indicate that P-450 IIEl is a major catalyst of the oxidation of benzene, styrene, CC4, CHC13, CH2C12,CH3C1, CH3CC13, 1,2-dichloropropane, ethylene dichloride, ethylene dibromide, vinyl chloride, vinyl bromide, acrylonitrile, vinyl carbamate, ethyl carbamate, and trichloroethylene. Levels of P-450 IIEl can vary considerably among individual humans-the availability of chlorzoxazo