Abstract
A single dose of carbon tetrachloride (CCl 4; 0·5, 1·0 or 2·0 ml/kg) administered to male Fischer rats greatly reduced the activities in rat-liver microsomes of N-nitrosodimethylamine (NDMA)-dimethylases I and II, operating at substrate concentrations of 4 and 200 mM, respectively. The repression in the enzyme activities was dose dependent. Microsomal protein and cytochrome P-450 contents were decreased. In contrast, feeding indole to rats at a level of 0·5 or 1% in the diet considerably increased the activities of both NDMA demethylases in a dose-dependent fashion. Demethylase activities were maximal after 6–12 days of indole feeding, and cytochrome P-450 was markedly increased. The inhibitory effect of CCl 4 on NDMA-demethylase I activity could be counteracted by feeding rats with indole. Although feeding indole significantly increased the level of cytochrome P-450, it only partially counteracted the decrease in this cytochrome produced by pretreatment with CCl 4.
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