Effects of intermediate metabolites of 37 xenobiotics on the catalytic activities of reconstituted cytochrome P-450IIB1 and P-450IA1 enzyme systems.

Direct effects of intermediate metabolites of 37 different xenobiotics on the catalytic activities of both reconstituted cytochrome P-450IIB1 and P-450IA1 enzyme systems were studied by determination of NADPH oxidation at various intervals after initiation of the reaction. The results showed that cytochrome P-450IIB1 isozyme was much more likely than cytochrome P-450IA1 isozyme to be attacked by the reactive intermediates formed by some xenobiotics with smaller molecular weight and lose its catalytic activities. These xenobiotics were carbon tetrachloride, chloroform, carbon disulfide, benzene, parathion, methylparathion, methyldursban and dimethylnitrosamine. In contrast, however, steadily increasing metabolic activities were observed towards benzo(a)pyrene, 3-methylcholanthrene and polychlorinated biphenyls in reconstituted cytochrome P-450IA1 enzyme system as the reaction time prolonged within 4 min. The method discussed in this paper could be used as a simple and convenient way to observe directly the autocatalytic destruction of P-450 enzymes by some chemical agents.