Huggins and Morii (J. Exp. Med., 114: 741, 1961) reported that massive adrenal
necrosis occurs in 79 and 100% of female Sprague-Dawley rats receiving 20 and 30 mg, respectively, of the mammary
carcinogen 7,12-dimethylbenz(a)anthracene (DMBA). Here, adrenal
necrosis and regeneration were studied in 158 rats for up to 21 days post-DMBA by radioautography of the adrenals of animals given 50 microCi [3H]
thymidine 30 min before sacrifice. Adrenal cell proliferation was markedly inhibited 21 days post-DMBA. Regenerated adrenals were more susceptible to this adrenocorticolytic effect. To investigate if alterations in adrenal function modify
tumorigenesis, animals underwent
adrenalectomies (ADX),
hypophysectomies,
ovariectomies, and pituitary transplants alone or in combination 6 days after receiving DMBA (20 mg/100 g intragastrically) at 50 days of age. To prevent adrenal
necrosis, 24 animals were pretreated with
metyrapone.
Methylprednisolone acetate, 1 mg i.m., was given to 40 animals every 5 days beginning 6 days post-DMBA. There were 50 non-DMBA-treated intact and surgical controls. DMBA was necessary but not sufficient to induce mammary
tumors. No
tumors developed in controls or in 46 animals hypophysectomized 6 days after DMBA.
Metyrapone reduced
tumor incidence and yield. ADX after DMBA treatment increased the tumorigenic response and eliminated resistance to
tumorigenesis in older rats. Only three
tumors developed in DMBA-treated rats receiving
methylprednisolone acetate. Mammary
tumorigenesis was increased by pituitary transplant 6 days after DMBA to intact and ADX animals.
Ovariectomy 6 days after DMBA was as effective as
methylprednisolone acetate in preventing
tumorigenesis; ADX did not overcome either inhibition. We conclude that adrenal
hormones inhibit proliferation of initiated mammary cells.