Inhibition of the Induction and Activity of Hepatic P450IA Isozymes by in Vivo Administration of Carbon Tetrachloride to Rats

The effect of carbon tetrachloride (CCl4) on the induction and activity of 3-methylcholanthrene (MC)-inducible P450IA isozymes (P450IA1 and P450IA2) in the liver was examined by treating male Sprague-Dawley rats with simultaneous i.p. injections of MC and CCl4. Following the treatment, the quantities of P450IA mRNAs determined by Northern blotting and P450IA proteins by Western blotting were significantly reduced as compared with those in rats treated with MC alone. As determined by a bacterial mutation test using carcinogenic aromatic amines are P450IA enzyme substrates, CCl4 treatment selectively inhibited the activity of P450IA2 in the MC-induced isozymes. These results indicate that CCl4 exerts on inhibitory effect on the induction of P4501A isozymes and that it selectively inhibits P450IA2 activity.