Mechanism of radiation carcinogenesis: role of the TGFBI gene and the inflammatory signaling cascade.

Using an immortalized human bronchial epithelial cell line, we showed previously that the transforming growth factor beta-induced (TGFBI) gene was consistently downregulated by six- to sevenfold among radiation-induced tumorigenic human cells when compared with controls. Transfection of TGFBI gene into tumor cells resulted in a significant reduction in tumor growth as well as in vitro anchorage independent growth. The observations that TGFBI knock-out animals showed increased spontaneous tumor incidence and chemically induced tumors highlight the suppressive nature of the gene. There is evidence that extranuclear/extracellular targets are important in low-dose radiation response and that the cyclo-oxygenase-2 signaling pathway mediates the process. The involvement of NFκB-dependent cytokines and the resultant inflammatory response works in concert with in modulating radiation-induced bronchial carcinogenesis.