Investigations on the mechanism of liver tumour induction by peroxisome proliferators.
Further understanding of the mechanism by which peroxisome proliferators induce liver tumours is essential to assessing the risks of such compounds to exposed humans. To this end the effects of nafenopin upon the liver have been investigated. Nafenopin was shown to induce certain drug metabolising enzymes, but sub-cellular fractions from induced animals did not form reactive metabolites which could be detected as mutagens. Nafenopin treatment slightly increased the rate of alkaline elution of hepatic nuclear DNA from polycarbonate filters. However, simultaneous administration of sodium glycolate to stimulate H2O2 production or pyrazole to inhibit catalase activity had no further effects. These findings demonstrate that nafenopin is not activated to a mutagen and argue against the hypothesis that indirect DNA damage as a result of excess H2O2 production is responsible for tumour induction.
D015660:7-Alkoxycoumarin O-Dealkylase; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D004247:DNA / Q000187:drug effects; D004790:Enzyme Induction / Q000187:drug effects; D006016:Glycolates / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000201:enzymology / Q000473:pathology; D008297:Male; D008830:Microbodies / Q000473:pathology*; D009255:Nafenopin / Q000494:pharmacology / Q000633:toxicity*; D010105:Oxygenases / Q000096:biosynthesis; D011422:Propionates / Q000633:toxicity*; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats
D006016:Glycolates; D011422:Propionates; D011720:Pyrazoles; D009255:Nafenopin; C031149:glycolic acid; C031280:pyrazole; D004247:DNA; D003577:Cytochrome P-450 Enzyme System; D006861:Hydrogen Peroxide; D010105:Oxygenases; D015660:7-Alkoxycoumarin O-Dealkylase