Molecular Pharmacology, Vol 9, 237-246, Copyright © 1973 by the American Society for Pharmacology and Experimental Therapeutics

Effects of Methylmercury on Microsomal Mixed-Function Oxidase Components of Rodents

¹ National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709

Preliminary treatment of rats with methylmercury hydroxide (10 mg/kg/day for 2 days) decreased hepatic cytochrome P-450 content by 52%, type I substrate (piperonyl butoxide) binding spectra by 40%, and type II substrate (aniline and metyrapone) binding spectra by 59% and 66%, respectively. Decreased cytochrome P-450 levels were apparently caused by increased degradation of the fast-phase component of the biphasic CO-binding pigment degradation curve. When chlordane, which decreases the degradation rate of the fast-phase component, was administered in conjunction with methylmercury hydroxide, the net effect was a degradation rate similar to controls. A control experiment was devised to demonstrate that the biphasic degradation curves were not influenced by heme exchange during preparation of subcellular particles from control, chlordane-treated, or methylmercurytreated rats. Rats exhibited the greatest methylmercury-induced decrease in cytochrome P-450 content, followed by mice and guinea pigs. Male rat liver P-450 was decreased more than that from female rats. Methylmercury was converted in substantial quantities to inorganic mercury in rats, mice, and guinea pigs. Microsomal mercury levels were highest in guinea pigs, followed by mice and rats.

Note:
ACKNOWLEDGMENTS Mercury analytical services were provided under contract by Dr. Paul Mushak, Department of Pathology, University of North Carolina, Chapel Hill. Thanks are extended to Miss Pat Singletary for excellent technical assistance.