Metabolic activation, detoxification and transformation studies with benzo[a]pyrene using rat and hamster organ cells in vitro.

Abstract

The mechanism of benzo[a]pyrene (BP) by cultured kidney, liver, small intestine, lung and trachea from male Syrian golden hamsters and Sprague-Dawley rats was compared. The metabolic capacity of intact cell systems was assessed by determining the formation of organic-solvent and water-soluble metabolites, levels of covalent binding and levels of BP metabolites following separation using high-pressure liquid chromatography. Hepatocytes from both species metabolized three to four times more BP than the other cells studied. Formation of water-soluble metabolites by hepatocytes was at least 10 times that of the other cell types. Generally, hamster cells had greater metabolic capability than rat cells. Levels of covalent binding of metabolites of BP were at least 10 times greater in hepatocytes (uninduced) from both species than in the other cell types. Binding to hepatocytes and hamster embryo cells increased with incubation time coinciding with an increase in the formation of water-soluble and diol metabolites. High levels of water-soluble metabolites accompanied high levels of covalent, whole-cell binding. Hamster embryo cells are transformed by BP without an exogenous metabolic activation system. The presence of hamster and rat hepatocytes inhibited transformation of hamster embryo cells by BP. This inhibition of transformation correlated with the increased rate of formation of water-soluble detoxification metabolites by hepatocytes from both species. The high rate of formation of water-soluble products by intact hepatocytes reflects the in vivo activity of liver cells. Use of hepatocytes in short-term tests allows a system for carcinogen metabolism more closely representing that which is present in the whole animal.