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Nickel Carbonyl Inhibition of Induction of Aminopyrine Demethylase Activity in Liver and Lung¹

Department of Laboratory Medicine, University of Connecticut School of Medicine, Hartford, Connecticut 06112 [F. W. S.], and Department of Pharmacology and Therapeutics, University of Florida College of Medicine, Gainesville, Florida 32601 [K. C. L.]

Exposure of rats to nickel carbonyl, Ni(CO)₄, in LD₅₀ dosage inhibited the basal (noninduced) levels of hepatic aminopyrine demethylase activity. The maximum inhibition of hepatic aminopyrine demethylase occurred on the 2nd day after an injection of Ni(CO)₄, and aminopyrine demethylase activity returned to normal levels by the 4th day after Ni(CO)₄. Administration of Ni(CO)₄ also inhibited hepatic aminopyrine demethylase activity in rats that had received daily injections of phenobarbital beginning 5 days before the Ni(CO)₄. However, in the phenobarbital-treated rats, maximum inhibition of hepatic aminopyrine demethylase did not occur until the 5th day after Ni(CO)₄ and aminopyrine demethylase activity did not return to normal levels until the 9th day after Ni(CO)₄. These experiments and other related studies indicate that Ni(CO)₄ inhibition of hepatic aminopyrine demethylase activity follows a distinctly different temporal sequence in noninduced and phenobarbital-treated rats.

The mean activity of aminopyrine demethylase activity in rat lungs was increased 2 days after ingestion of phenothiazine. Exposure of rats to Ni(CO)₄ inhibited the phenothiazine induction of pulmonary aminopyrine demethylase activity.

¹ This investigation was supported by U. S. Atomic Energy Commission Grant AT(30-1)4051, by American Cancer Society Grant E-374C, and by USPHS Grants CA-11250 and UI-00453. A preliminary report of this work appeared (38).

Received 10/24/69. Accepted 1/28/70.