INHIBITION OF THE DEVELOPMENT OF RAT-LIVER PRENEOPLASTIC LESIONS BY VERAPAMIL AND DEXVERAPAMIL

The effect of verapamil and dexverapamil on the development of liver p reneoplastic foci was investigated in male Sprague-Dawley rats initiat ed with N-nitrosodiethylamine (200 mg/kg i.p.), fed on a diet containi ng 0.01% 2-acetylaminofluorene and subjected to partial hepatectomy, a ccording to the hepatocarcinogenesis model developed by Solt and Farbe r. administration of drinking water containing 0.03% verapamil or dexv erapamil resulted in a decrease in the incidence and size of gamma-glu tamyl transpeptidase-positive foci. The chemopreventive effect of dexv erapamil was more marked than that of verapamil. These findings suppor t the hypothesis that these two calcium channel blockers act by reduci ng the resistance of initiated hepatocytes to the mitoinhibitory and c ytotoxic effects of 2-acetylaminofluorene.