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On the Mechanism of Inducing Protection of the Adrenal Cortex against Injury from 7,12-Dimethylbenz(a)anthracene

I. Effects of Inducers on Benzpyrene Hydroxylase Activity¹

Department of Breast Surgery, Roswell Park Memorial Institute, New York State Department of Health, Buffalo, New York

Benzpyrene (BP) hydroxylase activity in the liver, small intestine, adrenal, and mammary gland of normal rats has been quantitatively assayed. There was only a very small amount of enzyme activity in the mammary gland. Administration of 3-methylcholanthrene (3-MC) induced a marked increase in BP hydroxylase activity in the liver and intestine, but was without effect on the enzyme level in the mammary gland and the adrenals. Mammary gland and adrenals are not sites for hydroxylation of polycyclic aromatic hydrocarbons.

The capacities of polycyclic aromatic "protectors" and inactive compounds to induce BP hydroxylase synthesis were compared. When the doses of inactive "inducers" were increased severalfold, the level of BP hydroxylase activity in liver and intestine changed only slightly but a marked increase of adrenal protective activity was observed.

Sequential administration of hydrocarbons induced considerably larger amounts of BP hydroxylase than were evoked by either hydrocarbon separately; the induction of enzyme was more than additive if the combinations were 3-MC + 7,12-dimethylbenz(a)anthracene (DMBA) and DMBA + DMBA but was less than an arithmetic sum if the combinations were 3-MC + 3-MC and DMBA + 3-MC.

Actinomycin D, puromycin, and dl-ethionine inhibited 3-MC-induced stimulatory effect of BP hydroxylase activity. Under appropriate conditions of time, puromycin and dl-ethionine abolished the adrenal protection induced by aromatic hydrocarbons. Actinomycin D, under identical experimental conditions, had no effect on the adrenal protective activity induced by aromatic hydrocarbons. The possible mechanism by which protection of the adrenal cortex against injury from DMBA is discussed.

¹ This study was supported by Grant CA-04632-06 from the National Cancer Institute, NIH, USPHS.

Received 8/13/65. Revised 12/29/65.