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Inhibitory Effect of Polynuclear Hydrocarbons and Amphenone Analogs on Induction of Acute Adrenal Necrosis by 7,12-Dimethylbenz[a]anthracene^*

( Department of Breast Surgery, Roswell Park Memorial Institute [Department of Health, State of New York], Buffalo, New York)

A single feeding of an effective dose of any of the six polycyclic aromatic hydrocarbons including four carcinogens—DMBA, 3-MC, BP, and BA—and two noncarcinogens—anthracene and phenanthrene—48 hours prior to the administration of 30 mg. of DMBA completely inhibited the DMBA-induced adrenal necrosis. The minimal effective dose (to induce a 100 per cent protection against the DMBA-induced adrenal necrosis) for the four carcinogenic polycyclic hydrocarbons was 10 mg., and that for two noncarcinogens was 25 mg. for anthracene and 100 mg. for phenanthrene. Among the four carcinogens, 3-MC appears to provide the most effective protection against DMBA-induced adrenal necrosis. It is most remarkable to observe that a non-necrotizing dose of DMBA inhibited the necrosis-inducing effect of the same compound. The experimental results indicate that the presence of a critical amount of adrenocortical steroids in the adrenal gland is a prerequisite to the induction of necrosis by DMBA.

The present investigation demonstrated that, whereas Metopirone was partially effective in inhibition of DMBA-induced adrenal necrosis, o,p'-DDD, also an amphenone analog, was totally ineffective.

^* This study was supported by Grant CA-04632-04 from the National Cancer Institute, U.S. Public Health Service.

Received 3/29/63.