Inhibition of Dimethylbenzanthracene-Induced Adrenal Cortical Necrosis

Abstract

7,12-Dimethylbenzanthracene (DMBA), a carcinogenic polynuclear aromatic hydrocarbon, has been shown to cause selective necrosis in the zona fasciculata and zona reticularis of the adrenal cortex in young adult female Sprague-Dawley rats. This selective necrosis was attributed to the remarkable steric similarity between DMBA and hydroxycorticosteroids. It follows logically that the concomitant administration of compounds sterically similar to DMBA should lead to inhibition of the necrosis caused by the latter. The present paper reports the prevention of adrenal necrosis due to DMBA by the concurrent administration of 2 compounds, 2-methyl-l,2-bis-(3-pyridyl)-l-propanone(methopyrapone, Metopirone), and 3-(1,2,3,4- tetrahydro-l-oxo-2-naphthyl) -pyridine (Ciba Su-9055), both of which bear steric resemblance to DMBA. The possible mechanisms of action involved are discussed. (Endocrinology74: 284, 1964)