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Some Considerations on Molecular Structures of Polynuclear Hydrocarbons and Inhibition of Adrenal Necrosis in Rats^*

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

Previous studies demonstrated that some polycyclic aromatic hydrocarbons fed to rats 48 hours prior to the administration of 30 mg. of 7,12-dimethylbenz[a]anthracene (DMBA) protected the adrenal cortex against injury from DMBA. In the present investigation it was observed that the molecular structures of the hydrocarbons played an important role in determining their effectiveness for protection of the adrenal cortex against damage inflicted on it by DMBA. The data suggest that the most effective protectors are hydrocarbons with four or five benzene rings. Reduction of the molecular size of the hydrocarbon is accompanied by a marked decrease in protective activity. The molecular shape of the hydrocarbon does not appear to be an important factor.

Although alteration of the meso carbon atom of the anthracene molecule reduces the protective activity of the hydrocarbon, this effect can be compensated for by the addition of a benzene ring to the parent compound.

Among the steroid hormones studied, neither androgenic nor estrogenic compounds are effective in protecting the adrenal cortex against injury from DMBA. Under the present experimental conditions, adrenal cortical steroids were also ineffective. It was observed that protection of the adrenal cortex against induction of necrosis by moderate levels of DMBA significantly delayed the development of tumors but has little or no effect on the ultimate rate of mammary cancer induction.

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

Received 2/19/64.

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