Chemical carcinogenesis is accelerated in c-fos transgenic mice

Transgenic mice, having mouse proto-oncogene c-fos under the control of the promoter from murine major histocompatibility complex (MHC) class I gene (H2-Kb), have been established (c-fos mouse). C-fos mouse have been shown to produce high amount of exogenous c-fos protein in various organs. However, they do not develop any malignant tumors. In order to examine the effect of c-fos protein in oncogenesis, dorsal skin or lower gingiva of the mice were scratched and painted with 9,10-dimethyl-1,2-benzanthracene (DMBA) twice a week. C-fos mice showed squamous cell carcinoma in both skin and gingiva at 8 weeks after the treatment. On the contrary, control litter mate did not show any malignant change even at 11 weeks after the treatment. These results indicate that chemical carcinogenesis is accelerated in c-fos mice. Since the activities of immunosurveillance (e.g. natural killer (NK) cell and cytotoxic T lymphocyte (CTL)) in spleen cells from c-fos mice were significantly lower than those from control litter mate, effects of both the abnormal amount of c-fos protein and the partial defect of immunosurveillance in c-fos mice accelerate the induction of neoplasms in epithelial cells stimulated with DMBA.