INHIBITION BY VERAPAMIL OF HEPATOCARCINOGENESIS INDUCED BY N-NITROSOMORPHOLINE IN SPRAGUE-DAWLEY RATS

The effect of verapamil on hepatocarcinogenesis induced by N-nitrosomorpholine (NNM) was investigated in male Sprague-Dawley rats. Rats were given drinking water containing NNM for 8 weeks and received i.p. injections of verapamil or vehicle every other day for 16 weeks from the start of the experiment. Pre-neoplastic and neoplastic lesions staining positive for gamma-glutamyl transpeptidase (GGT) or the placental type of glutathione-S-transferase (GST-P) were examined histochemically at week 16. Prolonged administration of verapamil resulted in a significant decrease in the number of GGT-positive and GST-P-positive lesions. The incidence and volume as a percentage of parenchyma of hepatocellular carcinomas were also significantly less in rats treated with verapamil than in controls. Administration of verapamil significantly decreased the labelling indices of pre-neoplastic lesions and adjacent liver. These findings indicate that verapamil inhibits hepatocarcinogenesis and that this may be related to its inhibitory effect on cell proliferation in neoplastic lesions and surrounding hepatocytes.