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© 1992 Oxford University Press

research-article

Comparative Metabolism of Methyl Parathion in Intact and Subcellular Fractions of Isolated Rat Hepatocytes1

PRISCILLA N. ANDERSON, DAVID L. EATON2 and SHELDON D. MURPHY3

Department of Environmental Health SC-34, and Institute for Environmental Studies, University of Washington Seattle, Washington 98195

Received February 4, 1991; accepted August 23, 1991

Metabolism of the widely used insecticide methyl parathion by isolated hepatocytes and various subcellular fractions was compared to determine the effects of cellular integrity on the metabolic profile observed. A reverse-phase ion-pair high-performance liquid chromatographic method was developed to separate and quantify methyl parathion and six of its hepatic biotransformation products: methyl paraoxon; desmethyl parathion; desmethyl paraoxon; p-nitrophenol; p-nitrophenyl glucuronide; and p-nitrophenyl sulfate. Most compounds exhibited linear responses and limits of detection below 1 nmol. The chromatographic method was used to determine metabolic profiles of methyl parathion in isolated rat hepatocytes, sonicated hepatocytes, postmitochondrial fraction, microsomes, and cytosol. Isolated hepatocytes produced significantly more desmethyl parathion and p-nitrophenyl sulfate than the subcellular preparations, demonstrating that cellular integrity significantly affects the quantitative metabolic profile observed.


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