Protection against Dimethylnitrosamine Toxicity by Pregnenolone-16α-Carbonitrile

SINCE the discovery of the hepatotoxic¹ and carcinogenic² effect of dimethylnitrosamine (DMN), the significance of various nitroso-compounds as potential carcinogens in man has aroused increasing attention^3–8, especially since the demonstration of the endogenous production of nitrosocarcinogens from dietary amines or amides and sodium nitrite^9–15. Cellular damage resulting from exposure to nitrosamines has been attributed to unidentified metabolite(s) which alkylate nucleic acids, rather than to the parent compounds themselves^16–18 and certain agents (for example, aminoacetonitrile^19–21, polycyclic aromatic hydrocarbons^22,23, protein-free diet^24,25) which inhibit the metabolic degradation of DMN were subsequently found to reduce its acute toxicity and hepatocarcinogenicity.