Inhibition of induction of benzpyrene hydroxylase by nickel carbonyl.

Exposure of rats to nickel carbonyl by inhalation (0.2 mg Ni/liter of air/15 min) or intravenous injection (2 mg Ni/100 gm) was found to inhibit the induction of benzpyrene hydroxylase in lung and liver. Phenothiazine induction and fluorometric measurements of benzpyrene hydroxylase were performed by the methods of Wattenberg and co-workers (31, 32). Benzpyrene hydroxylase activities in lungs and livers of control rate were 9.5 (S.D. ±4.3) and 295 (S.D. ± 123) unite, respectively. Benzpyrene hydroxylase activities began to diminish 3 hours after administration of nickel carbonyl, reached a minimum at. 2 to 3 days, and remained diminished up to 1 week. For example, 52 hours after injection of nickel carbonyl, benzpyrene hydroxyl ase activities in lungs and livers were 1.1 ±1.0 (P < 0.01) and 113 ±24 (P < 0.01) unite, respectively. The inhibition of benzpyrene hydroxylase activity was apparently mediated either by diminished synthesis or increased catabolism of the enzyme, inasmuch as nickel carbonyl did not have any direct effect upon benzpyrene hydroxylase activity, in vivo or in vitro. It is sug gested that by inhibiting benzpyrene hydroxylation, nickel carbonyl may prolong the tissue retention of 3,4-benzpyrene and thereby promote carcinogenesis.