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EFFECT OF COADMINISTRATION OF PHENOBARBITAL SODIUM ON N-NITROSODIETHYLAMINE-INDUCED GAMMA-GLYTAMYLTRANSFERASE-POSITIVE FOCI AND HEPATOCELLULAR CARCINOMA IN RATS
Citation:
Pereira, M., S. Herren-Freund, A. Britt, AND M. Khoury. EFFECT OF COADMINISTRATION OF PHENOBARBITAL SODIUM ON N-NITROSODIETHYLAMINE-INDUCED GAMMA-GLYTAMYLTRANSFERASE-POSITIVE FOCI AND HEPATOCELLULAR CARCINOMA IN RATS. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-84/094 (NTIS PB84245620).
Description:
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/sq cm). At 30 weeks, the group treated with DENA and phenobarbital sodium exhibited more foci (23.6 foci/sq cm) compared to the group that received only DENA (3.08 foci/sq cm). 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.