Significance of immune responses to mucosal carcinogens: a hypothesis and a workable model system

Carcinogens must enter the tissues before neoplastic transformation of cells can occur. The present report describes the 2-AAF model system being used to test our hypothesis that development of mucosal immunity to carcinogens will interfere with their passage through mucosal epithelial cells. The 2-AAF model is ideal for testing this hypothesis. 2-AAF is a carcinogen which passes through the intestinal epithelium following oral administration, is transported to the liver and is there metabolized with the ultimate formation of hyperplastic nodules and neoplasms. Further, neoplasms form at other sites including the ear duct, gastrointestinal tract and the lungs. Our studies indicate that 2-AAF alone given orally does not elicit an immune response. However, 2-AAF is immunogenic when conjugated to carrier proteins and administered in CFA. Such conjugates of 2-AAF are not carcinogenic when administered in doses needed to achieve a systemic immune response in rats. Future studies will document the optimal conditions required to stimulate mucosal immunity to 2-AAF and the effect of such immunity on carcinogenesis in this model.