The effect of 13-cis-retinoic acid on hamster buccal pouch carcinogenesis

In order to determine whether 13-cis-retinoic acid, an analog of vitamin A, has antitumor activity in an oral cancer model system, the following study was undertaken. Fifty-three adult hamsters were divided into four groups. Group 1 was tested with a 0.5 percent solution of 9,10-dimethyl-1,2-benzanthracene (DMBA) in heavy mineral oil, which was painted on the right buccal pouch three times per week for 12 weeks. Group 2 received DMBA plus 13-cis-retinoic acid (RA) incorporated into gelatinized beadlets and mixed with a powdered commercial diet (dosage, 300 mg per kilogram of diet). Group 3 received only RA; Group 4 received a placebo. The animals were killed at 6, 12, and 18 weeks and tissues were studied clinically and histologically in a routine manner. Results show that all groups receiving DMBA developed epidermoid carcinomas. However, there were several other changes. In the RA-treated animals, particularly those treated with DMBA, there was an ingrowth of surface epithelium with development of ductal structures in the buccal pouch. There were changes in surface epithelium, and there were dense aggregates of lymphoid tissue with development of exophytic nodules suggestive of lymphoma. Animals fed RA showed a relative weight loss. The findings suggest that there was a hypervitaminosis A state yielding prominent epithelial metaplastic changes but not affecting the progression or production of carcinoma.