Inhibition of the development of rat liver preneoplastic lesions by verapamil and dexverapamil.
The effect of verapamil and dexverapamil on the development of liver preneoplastic foci was investigated in male Sprague-Dawley rats initiated with N-nitrosodiethylamine (200 mg/kg i.p.), fed on a diet containing 0.01% 2-acetylaminofluorene and subjected to partial hepatectomy, according to the hepatocarcinogenesis model developed by Solt and Farber. Administration of drinking water containing 0.03% verapamil or dexverapamil resulted in a decrease in the incidence and size of gamma-glutamyl transpeptidase-positive foci. The chemopreventive effect of dexverapamil was more marked than that of verapamil. These findings support the hypothesis that these two calcium channel blockers act by reducing the resistance of initiated hepatocytes to the mitoinhibitory and cytotoxic effects of 2-acetylaminofluorene.
Ghia
M
M
Institute of Pharmacology, University of Genoa, Italy.
Mereto
E
E
Cavanna
M
M
Brambilla
G
G
D015073:2-Acetylaminofluorene; D000704:Analysis of Variance; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000032:analysis; D002273:Carcinogens; D004052:Diethylnitrosamine; D006498:Hepatectomy; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008113:Liver Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D011230:Precancerous Conditions / Q000139:chemically induced / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014700:Verapamil / Q000494:pharmacology*; D005723:gamma-Glutamyltransferase / Q000032:analysis
D016588:Anticarcinogenic Agents; D014408:Biomarkers, Tumor; D002273:Carcinogens; D004052:Diethylnitrosamine; D015073:2-Acetylaminofluorene; D014700:Verapamil; D005723:gamma-Glutamyltransferase