Differential effects of beta-naphthoflavone and pregnenolone-16alpha-carbonitrile on dimethylnitrosamine-induced hepatocarcinogenesis.
The effect of administration of beta-naphthoflavone (beta-NF) or pregnenolone-16alpha-carbonitrile (PCN) on the hepatocarcinogenicity of dimethylnitrosamine (DMN) in male SD rats was explored. Both beta-NF and PCN are potent repressors of the low Michaelis constant enzymatic form of DMN-demethylase, a mixed-function oxidase that catalyzes DMN demethylation. DMN-induced hepatocarcinogenesis was inhibited by PCN and was enhanced by beta-NF. Seven liver tumors were found in 45 rats fed DMN plus PCN compared to 14 liver tumors in 43 rats fed DMN alone; 32 liver tumors were found in 43 rats fed DMN plus beta-NF. No liver tumors were detected in rats that received only PCN, beta-NF, or the administration vehicles. Of the 53 liver tumors observed, 53% were angiosarcomas; this type of tumor was found in all 3 groups of rats that received DMN.
D000818:Animals; D001711:Biotransformation / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced / Q000473:pathology; D004128:Dimethylnitrosamine / Q000037:antagonists & inhibitors; D004347:Drug Interactions; D005419:Flavonoids / Q000494:pharmacology*; D006394:Hemangiosarcoma / Q000139:chemically induced / Q000473:pathology; D008113:Liver Neoplasms / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D009281:Naphthalenes / Q000494:pharmacology; D009374:Neoplasms, Experimental / Q000139:chemically induced; D009602:Nitrosamines / Q000037:antagonists & inhibitors; D010089:Oxidoreductases, N-Demethylating / Q000037:antagonists & inhibitors; D011285:Pregnenolone Carbonitrile / Q000494:pharmacology*; D051381:Rats
D005419:Flavonoids; D009281:Naphthalenes; D009602:Nitrosamines; D011285:Pregnenolone Carbonitrile; D010089:Oxidoreductases, N-Demethylating; D004128:Dimethylnitrosamine