Effect of coadministration of phenobarbital sodium on N-nitrosodiethylamine-induced gamma-glutamyltransferase-positive foci and hepatocellular carcinoma in rats.
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 gamma-glutamyltransferase (gamma-glutamyltranspeptidase) (GGT)-positive foci and liver tumors. Male outbred 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.
D000818:Animals; D004052:Diethylnitrosamine / Q000633:toxicity*; D004347:Drug Interactions; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000201:enzymology / Q000473:pathology*; D008297:Male; D009602:Nitrosamines / Q000633:toxicity*; D010634:Phenobarbital / Q000633:toxicity*; D011230:Precancerous Conditions / Q000139:chemically induced / Q000201:enzymology / Q000473:pathology*; D051381:Rats; D011919:Rats, Inbred Strains; D005723:gamma-Glutamyltransferase / Q000378:metabolism*
D009602:Nitrosamines; D004052:Diethylnitrosamine; D005723:gamma-Glutamyltransferase; D010634:Phenobarbital