Nickel carbonyl inhibition of cortisone induction of hepatic tryptophan pyrrolase.

Administration of nickel carbonyl to rats by intravenous in jection (2 mg Ni/100 gm body weight) inhibited the induction of hepatic tryptophan pyrrolase by cortisone but not by tryptophan. Cortisone induction was impaired on the day after admin istration of nickel carbonyl. It reached a minimum at 2 days and remained diminished for 5 days. The average activity of hepatic tryptophan pyrrolase in cortisone-treated control rats was 36 (S.D. ±7)units, compared with an average activity of 20 ±4 units in similar rats that received nickel carbonyl 2 days before sacrifice (P < 0.01). Cortisone induction of tryptophan pyrrolase was inhibited by nickel carbonyl in adrenalectomized rats as well as in normal rats. Nickel carbonyl did not inhibit tryptophan pyrrolase activity in vitro. The finding that nickel carbonyl inhibited induction of tryptophan pyrrolase by cortisone but not by tryptophan suggests that the toxic effect of nickel carbonyl on enzyme induction is mediated either by diminished synthesis or denaturation of messenger RNA.