Invariably in every normal rat a single dose of 7, 12-dimethylbenz(a)anthracene, by mouth or injected in a vein, was found to cause apoplexy and massive necrosis in the inner zones of the adrenal cortex; the zona glomerulosa, the adrenal medulla, and a small region of cortex adjacent to the great adrenal vessels were spared from damage. DMBA caused these selective lesions in females and in males of 2 strains of rats. Hemorrhage and necrosis were observed in no organ other than the adrenal gland. Whereas adrenal glands were heavily damaged by DMBA, pituitary and ovary escaped injury by the compound.

A single huge but sublethal feeding of o, p'-DDD caused degenerative changes of minor magnitude in the adrenals and only in a small percentage of rats; the property of inducing adrenal damage was not shared by other polynuclear aromatic hydrocarbons which were investigated, including strong carcinogens.

Presence of adrenal medulla is not a prerequisite to damage of the adrenal cortex by DMBA. The adrenal damage occurred in rats, given DMBA, from which the pituitary had been removed but the lesions were smaller in extent and less in incidence as post-hypophysectomy atrophy of the adrenal cortex progressed.

The entire DMBA molecule was necessary to induce adrenal damage; fragments of this molecule did not induce adrenal lesions. Two components which are of cardinal importance in this specific damaging effect are: (a) electronic factor; (b) steric factor.

The level of isocitric dehydrogenase in adrenal is modified considerably by presence or absence of estradiol-17ß.

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