Role of Lysosomes in Adrenal Necrosis caused by Dimethylbenzanthracene

Abstract

IT has long been recognized that carcinogenic chemicals, including polybenzenoid hydrocarbons, have injurious effects on cells^1,2. Evidence has been presented that polybenzenoid hydrocarbons are concentrated in the lysosomes of living cells and the suggestion was made that release of lysosomal enzymes may play an important part in their cytotoxic action³. The necrosis of rat adrenal cortical cells produced by 7,12-dimethylbenz(a)anthracene (DMBA)⁴ provided an opportunity to test this hypothesis in more detail, because it is specific in two ways. First, the degeneration is organ specific, adrenal cortical cells of the rat being much more sensitive than the cells of other organs. Secondly, it appears to be specifically produced by one compound, 7-hydroxymethyl-12-methylbenz(a)anthracene (7-OHM-12-MBA), which is a metabolite of DMBA: an isomeric metabolite, 12-hydroxymethyl-7-methylbenz(a)anthracene (12-OHM-7-MBA), does not produce adrenal damage⁵. Rats can be protected against adrenal damage after administration of DMBA by previous treatment with a number of aromatic hydrocarbons and amines, which diminish the formation of 7-OHM-12-MBA from DMBA⁵. Hence it seems that the metabolite is more active than the parent compound in producing adrenal necrosis.