Fifty young adult male and female albino rats were studied for the effect of systemically administered cyclophosphamide upon chemical carcinogenesis of the submandibular gland. In 1 group of animals, pellets of 9,10-dimethyl-1,2-benzanthracene (DMBA) were implanted into the right submandibular glands. A 2nd group of animals received biweekly i.p. injections of cyclophosphamide (Cytoxan) in addition to DMBA implants into the right submandibular glands. Animals were sacrificed at 13 to 17 weeks after DMBA implantation. In the DMBA animals, well-differentiated epidermoid carcinomas developed within epidermoid cysts. In the DMBA-cyclophosphamide animals, the epidermoid carcinomas developed more rapidly and were more anaplastic histologically. In the DMBA-cyclophosphamide animals, fibrosarcomas and adenocarcinomas developed in addition to the epidermoid carcinomas. The augmentation of the salivary gland carcinogenesis was interpreted in terms of a depression of the immune response to tumor development by the cyclophosphamide.

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