Benzene Metabolism by Two Purified, Reconstituted Rat Hepatic Mixed Function Oxidase Systems
Benzene, a bone marrow depressant, requires metabolism in order to exert its hematopoetic toxicity (Snyder et al., 1980). In mammals, this metabolism ccurs primarily in the liver and is catalyzed by the cytochrome P-450 containing mixed function oxidase (MFO) system (Gonasun et al., 1973). Post and Snyder (1983) demonstrated that rat liver microsomes contain at least two, distinct MFO activities which can metabolize benzene. One is induced by phenobarbital (PB) pretreatment and displays a Km value greater than 10mM; the other is induced by benzene pretreatment and displays a Km value equal to approximately 0.1mM. PB pretreatment results in the induction of cytochrome P450IIB1 (Ryan et al., 1979), while benzene pretreatment appears to induce cytochrome P450IIE1 (Ingelman-Sundberg and Johansson, 1984). Koop et al. (1989) demonstrated that P45011E1, purified from rabbit liver microsomes, is an effective benzene hydroxylase. In this study, we have examined benzene metabolism by two purified, reconstituted rat hepatic MFO systems containing either cytochrome P450IIB1 or P450IIE1.
KeywordsMixed Function Oxidase Lower Substrate Concentration Mixed Function Oxidase System Hepatic Microsomal Cytochrome Liver Microsomal Cytochrome
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