The Effect of Dietary Phenobarbital on the Induction of Skin Tumors in Hairless Mice with 7,12-Dimethylbenz[A]Anthracene

Abstract

Since phenobarbital is known to induce drug-metabolizing enzymes and to alter the effectiveness of certain carcinogens, its influence on 7,12-dimethylbenz[a]anthracene (DMBA)-induced skin carcinogenesis has been examined. Skin tumor development was studied in groups of hairless mice treated with repeated applications of DMBA and maintained on either a control diet or one supplemented with 0.05% phenobarbital. The feeding of phenobarbital concurrently with the application of DMBA delayed the appearance of papillomas initially, but the suppression of the ultimate tumor yield was variable, and appeared to be dependent on the dose of the carcinogen and the age-dependent toxicity response of the mice. Phenobarbital was ineffective when DMBA was applied in sufficiently large amounts to elicit marked cutaneous damage, or when dietary phenobarbital was started 1 week after the cessation of the DMBA treatment. Although the dietary administration of phenobarbital caused an apparent decrease in the final incidence of papillomas and sarcomas, the feeding did not appear to modify the macroscopic skin response or change the incidence of carcinomas.