GUENGERICH, FP KIM, DH IWASAKI, M 2024-01-21T23:46:18Z 2024-01-21T23:46:18Z 2022-01-11 1991-03 0893-228X https://pubs.kist.re.kr/handle/201004/146825 The role of human cytochrome P-450 IIE1 (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 IIE1 is a major catalyst of the oxidation of benzene, styrene, CCl4, CHCl3, CH2Cl2, CH3Cl, CH3CCl3, 1,2-dichloropropane, ethylene dichloride, ethylene dibromide, vinyl chloride, vinyl bromide, acrylonitrile, vinyl carbamate, ethyl carbamate, and trichloroethylene. Levels of P-450 IIE1 can vary considerably among individual humans-the availability of chlorzoxazone as a noninvasive probe of human P-450 IIE1 and of disulfiram (oxidized diethyldithiocarbamate) as an inhibitor may facilitate discernment of the in vivo significance of human P-450 IIE1 as a factor in the bioactivation and detoxication of these cancer suspects. Further, many investigations with diethyldithiocarbamate, disulfiram, and ethanol in humans and experimental animals may be interpreted in light of mechanisms involving P-450 IIE1. English AMER CHEMICAL SOC LIVER MICROSOMAL CYTOCHROME-P-450 RAT-LIVER CARBON-TETRACHLORIDE GENETIC-POLYMORPHISM DRUG-METABOLISM N-NITROSODIMETHYLAMINE ETHYL CARBAMATE 2-CYANOETHYLENE OXIDE IRREVERSIBLE BINDING INVITRO METABOLISM ROLE OF HUMAN CYTOCHROME-P-450-IIE1 IN THE OXIDATION OF MANY LOW-MOLECULAR-WEIGHT CANCER SUSPECTS Article 10.1021/tx00020a008 1 CHEMICAL RESEARCH IN TOXICOLOGY, v.4, no.2, pp.168 - 179 CHEMICAL RESEARCH IN TOXICOLOGY 4 2 168 179 scie scopus A1991FC03000008 2-s2.0-0026035519 Chemistry, Medicinal Chemistry, Multidisciplinary Toxicology Pharmacology & Pharmacy Chemistry Toxicology Article LIVER MICROSOMAL CYTOCHROME-P-450 RAT-LIVER CARBON-TETRACHLORIDE GENETIC-POLYMORPHISM DRUG-METABOLISM N-NITROSODIMETHYLAMINE ETHYL CARBAMATE 2-CYANOETHYLENE OXIDE IRREVERSIBLE BINDING INVITRO METABOLISM