Inhibitory effect of nafenopin upon the development of diethylnitrosamine-induced enzyme-altered foci within the rat liver

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Abstract
The effect of nafenopin and phenobarbitone upon the distribution of γ-glutamyltranspeptidase activity and epoxide hydrolase antigenic sites in the liver and upon the development of enzyme-altered foci during hepatocarcinogenesis have been compared. Phenobarbitone induced γ-glutamyltranspeptidase activity in perilobular hepatocytes. Nafenopin did not alter the distribution of this enzyme. Both compounds appeared to induce epoxide hydrolase; phenobarbitone increased the enzyme content of centrilobular cells, whilst nafenopin altered immunostaining mainly in portal regions. Hepatic lesions were induced by treating one day-old rats with diethylnitrosamine. Phenobarbitone and nafenopin were then administered in the diet upon weaning. Animals were killed after either 2, 4 or 8 weeks feeding and liver sections were stained for the two enzymes. Only sections from nitrosamine-treated animals contained enzyme-altered foci. In general, γ-glutamyltranspeptidase-containing foci stained also for epoxide hydrolase; but many hydrolasepositive foci did not stain for γ-glutamyltranspeptidase activity. Phenobarbitone treatment stimulated the formation of enzymealtered foci. This effect was more marked in male animals. Nafenopin treatment suppressed the development of foci at all time points, such that less hepatic lesions were seen than in animals which received only diethylnitrosamine. The results cast doubt upon the generality of γ-glutamyltranspeptidase as a marker for preneoplastic lesions within the liver.