Immunologic aspects of ultraviolet carcinogenesis.

Chronic treatment of mice with ultraviolet (UV) light induces highly antigenic tumors that usually are rejected immunologically upon transplantation to normal syngeneic recipients. This raised the question of how such tumors became established and grew progressively in the primary host. The nature of the mechanism underlying this failure of the immune system to deal with these antigenic tumors in the primary host has investigated. The immune status of the primary host towards its own developing tumor was evaluated immediately after surgical removal of the primary tumor. All primary hosts were susceptible to challenge with their autochthonous tumors, though most of these tumors were rejected by untreated syngenic secondary hosts. Primary hosts also were susceptible to challenge with isografts of antigenically dissimilar UV-induced tumors. The susceptibility of the primary hosts to tumor challenge was probably induced by chronic exposure to UV light, since UV-irradiated non-tumor-bearing mice also were susceptible to challenge with thee tumors. Thus, UV light inducted a systemic alteration that resulted in the failure of UV-irradiated mice to reject UV-induced tumors which were rejected by non-irradiated recipients. Continuous UV-treatment was not necessary for the maintenance of the systemic defect since cessation of UV-treatment failed to restore the animal's ability to reject a UV-induced tumor. Although UV-treated mice were unable to reject these syngeneic tumors, they could reject tumor allografts. Moreover, UV-irradiation did not interfere with the second-set rejection of syngeneic UV-induced tumors in mice that were specifically immunized before UV-treatment. The immunologic aspects of this systemic alteration were demonstrated by transferring lymphoid cells from UV-irradiated mice to lethally X-irradiated recipients. These recipients were unable to resist a later challenge with a syngeneic UV-induced tumor, whereas those recipients given lymphoid cell from normal donors were resistant to tumor growth. To determine whether this alteration was due to the absence of reactive cells or the presence of suppressor cells, mixtures of equal numbers of lymphoid cell form UV-irradiated and normal donors were injected intravenously into lethally x-irradiated recipients. These recipients were unable to resist the growth of these UV-induced tumor implants, suggesting the presence of suppressor cells. Parabiosis of normal mice with UV-irradiated mice, followed by tumor challenge of both parabionts with a UV-induced tumor, resulted in the growth of challenge tumors in both UV-irradiated and un-irradiated mice. Splenic lymphocytes from tumor-implanted UV-treated mice were not cytotoxic in vitro against UN-induced tumors, whereas under identical conditions, cells from tumor-implanted, non-irradiated mice were highly cytotoxic. These findings suggested that repeated UN-irradiation can circumvent an immunologic mechanism that might otherwise nascent highly antigenic UV-induced primary tumors.