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The Effect of Benzpyrene, Phenobarbital, and Carbon Tetrachloride on Subcellular Metal Distribution and Microsomal Enzyme Activity

Laboratory of Toxicology and Pathology, National Institute for Occupational Safety and Health, Health Services and Mental Health Administration, USPHS, Cincinnati, Ohio 45202

Alterations in the normal subcellular metal distribution of rat liver and lung have been produced by the acute administration of phenobarbital, carbon tetrachloride, and intratracheal 3,4-benzpyrene. Following the isolation of the various subcellular fractions by a standard technique, the metal composition of the subfractions was determined by atomic absorption spectrophotometry and expressed as µg metal per mg nitrogen.

Significant increases in lung microsomal copper and manganese and significant decreases in microsomal nickel and chromium were observed at 72 hr after intratracheal administration of 3,4-benzpyrene, at a dose which produced a 6-fold increase in lung 3,4-benzpyrene hydroxylase activity. The administration of phenobarbital (75 mg/kg) to rats for 3 days produced significant increases in liver microsomal copper, manganese, and zinc levels. In contrast, the administration of a subacute dose of carbon tetrachloride (0.5 ml/kg) produced a significant reduction of liver microsomal copper, manganese, and zinc, as well as a marked depression of liver aniline hydroxylase activity.

The subcellular metal changes observed in this study may reflect a redistribution of endogenous metal stores in the enzyme-responsive tissue, since these changes cannot be explained by alterations in the whole-organ metal content or the nitrogen content of the subfractions.

¹ Present address: Kresge Center for Environmental Health, Harvard University School of Public Health, 665 Huntington Avenue, Boston, Mass. 02115.

Received 12/14/71. Accepted 2/25/72.