Activities of benzphetamine N-demethylase and aryl hydrocarbon hydroxylase in cells isolated from gamma-glutamyl transpeptidase-positive foci and surrounding liver

Abstract

The levels of two cytochrome P-450-linked enzymes of xenobiotic metabolism, benzphetamine N-demethylase and aryl hydrocarbon hydroxylase, were determined in cells isolated from gamma-glutamyl transpeptidase (GGT)-positive foci and in cells from surrounding liver obtained from carcinogen-treated inbred F344 rats. Rat liver foci were initiated with diethylnitrosamine (CAS: 55-18-5) and promoted with sodium phenobarbital [(PB) CAS: 64038-21-7] for 4 1/2 or 12 months. The levels of both enzymes were relatively low in the GGT-positive hepatocytes, while the GGT-negative hepatocytes from the surrounding liver had elevated levels of both enzymes comparable to levels seen in rats treated with PB alone. After 12 months of promotion the PB was removed from the diet and the activities of both enzymes fell below the control levels in the GGT-positive hepatocytes and returned to the control levels in the surrounding GGT-negative hepatocytes. Therefore, the cells in the GGT-positive foci contained low levels of these two cytochrome P-450 enzymes in relation to the levels in GGT-negative cells. These levels were responsive to phenobarbital induction, although the induced levels in the GGT-positive cells were much lower than the induced levels in GGT-negative hepatocytes. The liver surrounding the foci responded to phenobarbital induction to the same degree as did the liver of noninitiated rats.