Enhancement of two-stage skin carcinogenesis by exposure of distant skin to UV radiation.

Exposure of C3H/HeN mice to UV 280-320 nm (UVB) radiation induces a systemic, immunologic alteration that interferes with the rejection of highly antigenic UVB radiation-induced skin cancers. The effect of this systemic alteration, induced by ventral UVB irradiation of mice, was tested on the induction of dorsal skin tumors resulting from initiation with UVB radiation and promotion with 12-O-tetradecanoylphorbol 13-acetate (TPA). The systemic effect of UVB radiation markedly potentiated carcinogenesis at the distant site. More important, mice treated with TPA alone on the dorsal skin developed a significant number of dorsal tumors if the mice also had been exposed ventrally to UVB radiation. Treatment of dorsal skin with UVB radiation alone did not result in the development of cancers, regardless of whether the mice received ventral irradiation. These results suggest that the systemic effect of UVB radiation is exerted during the promotion phase of two-stage carcinogenesis. Furthermore, they imply that a systemic effect of UVB radiation interferes with a natural host control mechanism that ordinarily holds skin cancers in check.