The disturbance of oxidative phosphorylation in rat liver mitochondria by the carcinogens 12-hydroxystearic acid and its methyl ester.
In a search to determine common molecular features in potential carcinogenic dietary fatty acids, Swern et al. (1970) found that 12-hydroxystearic acid and its methyl ester were carcinogenic. This was surprising to Swern et al. (1970) and Van Duuren et al. (1972), as it was not readily apparent how such agents could be converted to alkylating agents. We have observed that the carcinogens 12-hydroxystearic acid and its methyl ester disrupted oxidative phosphorylation in rat liver mitochondria. The in vitro mitochondrial effects induced by the agents included: a) uncoupled respiration, b) ATPase activity, c) energized volume changes linked either to respiration or ATP. Mitochondria mediated the enzymic conversion of the ester to the acid. Conversion was retarded by the thiol reagent showdomycin. These data in conjuction with our previous reports dealing with other carcinogens and their derivatives contribute to an experimental confluence between oxidative phosphorylation and chemical carcinogenesis.
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002273:Carcinogens / Q000494:pharmacology*; D066298:In Vitro Techniques; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D008933:Mitochondrial Swelling / Q000187:drug effects; D010085:Oxidative Phosphorylation / Q000187:drug effects*; D051381:Rats; D012787:Showdomycin / Q000494:pharmacology; D013229:Stearic Acids / Q000494:pharmacology*
D002273:Carcinogens; D013229:Stearic Acids; D000255:Adenosine Triphosphate; D012787:Showdomycin; D000251:Adenosine Triphosphatases