INDUCED PROTECTION OF ADRENAL CORTEX AGAINST 7,12-DIMETHYLBENZ[a]ANTHRACENE

Abstract

7,12-Dimethylbenz[a]anthracene (7,12-DMBA) exerts adrenocorticolytic effects which set it apart from all other polynuclear aromatic hydrocarbons and aromatic amines which have been investigated. Adrenal damage by this compound appears to be due to its steric and electronic properties together with its unusually high solubility in lipides. Many compounds given prior to 7,12-DMBA induced protection of adrenal. The most efficient inducers of protection are flat condensed aromatics possessing 4 or 5 rings; very small doses of these compounds were required to induce protection. Other compounds devoid of these properties induced protection but large or repeated doses were necessary. All inducers of protection had to be given prior to 7,12-DMBA to prevent adrenal necrosis; when given simultaneously with, or later than, this compound adrenal apoplexy resulted. Protective aromatics and 7,12-DMBA as well induced synthesis of menadione reductase in liver. 3-Methylcholanthrene (3-MC) induced this enzyme in many normal organs including liver, lung, adrenal, and in mammary cancer as well. dl-Ethionine under appropriate conditions of time and dosage eliminated the adrenal protection induced by aromatics and also delayed the induction of menadione reductase while depressing the amount of this enzyme which was synthesized. 7,12-DMBA caused a greatly reduced incorporation of tritium from thymidine-H3 into washed acid-insoluble residue of adrenal. 3-MC given in advance mitigated the drastic effect of 7,12-DMBA on DNA synthesis and increased considerably the amount of tritium which was incorporated. The specific damage to adrenal by 7,12-DMBA is a direct effect on cells. Protection of adrenal is a secondary effect which requires induction of protein synthesis and it results in improvement in synthesis of DNA.