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Effect of Polychlorinated Biphenyls (Aroclor 1254) on Inducible and Repressible Microsomal N-Demethylases in the Mouse and Rat¹

Seamen's Memorial Research Laboratory, USPHS Hospital, 210 State Street, New Orleans, Lousiana 70188; and Department of Medicine, Tulane University Medical Center, New Orleans, Louisiana

A comparative study of the effects of the polychlorinated biphenyl mixture Aroclor 1254, 3-methylcholanthrene, and starvation on hepatic dimethylnitrosamine (DMN) demethylase (a repressible enzyme) and azo dye N-demethylase (an inducible enzyme) has been carried out. As previously observed with polycyclic hydrocarbons and phenobarbital, Aroclor in rats is a potent inducer of liver tissue proliferation and of azo dye N-demethylase, as well as a potent repressor of DMN demethylase. However, in mice, although the inducing effect on liver tissue proliferation and azo dye N-demethylase activity is maintained, there is no change in DMN demethylase activity as a result of Aroclor administration. As in rats, 3-methylcholanthrene induces the azo dye N-demethylase in mice. This hydrocarbon, which is known to substantially repress the DMN demethylase in rats, has, however, no effect on this enzyme in mice. While starvation is known to have a substantial inducing effect on DMN demethylase in rats, in mice starvation brings about a moderate induction of DMN demethylase.

¹ This investigation was supported by USPHS Research Grant CA-13206 from the National Cancer Institute. Financial aid from Hoffmann LaRoche Inc., through the kindness of Dr. Allan H. Conney, is gratefully acknowledged.

² Recipient of a Faculty Research Award from the American Cancer Society.

Received 7/26/74. Accepted 3/11/75.