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The Influence of Adrenal Injury Produced in Rats by 7, 12-Dimethylbenz[]anthracene on the Regulation of Liver Tyrosine Aminotransferase and Tryptophan Oxygenase¹

Cancer Research Institute, New England Deaconess Hospital, and the Departments of Biological Chemistry and Pathology, Harvard Medical School, Boston, Massachusetts 02215

The morphologic damage to the adrenals and the behavior of 2 liver enzymes (tyrosine aminotransferase and tryptophan oxygenase) that are regulated by the adrenals were studied in 2 strains of rats treated with 7,12-dimethylbenz[]anthracene at 50 days of age. The induction of these enzymes by reserpine, acting through the pituitary-adrenal system, was used as a measure of the ability of the adrenals to secrete glucocorticoids.

In both strains of rats, the adrenocortical damage was maximal and the enzyme response to reserpine was minimal 3 days after the administration of 7,12-dimethylbenz[]anthracene, thus providing a correlation between the histopathologic changes and the function of the adrenal glands.

The initial stresslike effect of 7,12-dimethylbenz[]anthracene on the liver enzymes, seen at 5 hr, was smaller in the Sprague-Dawley rats in which 7,12-dimethylbenz[]anthracene caused a higher tumor incidence. The basal enzyme levels and their induction by reserpine were also lower in these rats than in NEDH rats. These differences between the 2 strains diminish with age, which suggests that at the critical age of 50 days when the carcinogen is administered, the pituitary-adrenal system may be less fully developed in the Sprague-Dawley strain which has the higher tumor incidence.

¹ This investigation was supported by USPHS Grant CA 08676 and by U. S. Atomic Energy Commission Contracts AT(30-1)-3777 and AT(30-1)-3779 with the New England Deaconess Hospital.

Received 4/10/67. Accepted 6/22/67.