Effect of Coadministration of Phenobarbital Sodium on N-Nitrosodiethylamine-Induced γ-Glytamyltransferase-Positive Foci and Hepatocellular Carcinoma in Rats

Abstract

The effect of concurrent administration of phenobarbital on the hepatocarcinogenicity of N-nitrosodiethylamine (diethylnitrosamine; DENA) in rats was investigated by determination of the incidence of γ-glutamyltransferase (γ-glutamyl-transpeptidase) (GGT)-positive foci and liver tumors. Male out-bred Sprague-Dawley rats received either a weekly oral dose of DENA (0.08 mol/kg), phenobarbital sodium (500 ppm) in their drinking water, or DENA and phenobarbital sodium concurrently. After 16 weeks, only the animals treated concurrently with DENA and phenobarbital sodium had GGT-positive foci (3.65 foci/cm²). At 30 weeks, the group treated with DENA and phenobarbital sodium exhibited more foci (23.6 foci/cm²) compared to the group that received only DENA (3.08 foci/cm²). The average size of foci in both of the DENA-treated groups was the same. The tumors in the group that received DENA plus phenobarbital sodium showed a greater incidence of GGT activity compared to the tumors in the DENA group. Under the conditions of this study the incidence of GGT-positive foci did not predict the incidence of hepatocellular carcinomas.