COMPARISON OF DOSE-DEPENDENT ENHANCING EFFECTS OF GAMMA-RAY IRRADIATION ON URETHANE-INDUCED LUNG TUMORIGENESIS IN ATHYMIC NUDE (NU NU) MICEAND EUTHYMIC (NU/+) LITTERMATES/

The role of immunological surveillance in carcinogenesis is still cont roversial. In our previous experiments, urethan-induced lung tumorigen esis in athymic (nu/nu) mice and euthymic (nu/+) littermates was exami ned, and it was concluded that immunosurveillance mediated by T cells could not be demonstrated. However, the reported enhancement of develo pment of various tumors following ionizing radiation might be achieved through modulating the host immunological conditions. In the present experiment, nu/nu and littermate nu/+ mice were treated with 1-4 Gy ga mma-rays alone at 6 weeks of age or treated with urethan at 0.5 mg/g b ody weight when aged 14 days followed by 1-4 Gy gamma-rays 4 weeks lat er. Lung tumors were assessed at 6.5 months of age. Ionizing radiation itself caused a very low incidence of these lesions. On the other han d, multiplicities and incidences of lung tumors after urethan treatmen t at 0.5 mg/g body weight were similar between the two phenotypically different groups of mice (1.66 and 1.84 tumors/mouse, 73% and 80% inci dences, for nu/nu and nu/+ cases respectively). This urethan-induced l ung tumorigenesis was significantly enhanced by gamma-rays in both nu/ nu and nu/+ mice, and the magnitude of tumor enhancement was somewhat higher in nu/+ mice than in nu/nu mice, especially with a 2-Gy dose. I n conclusion, it may be said that lung tumorigenicity of gamma-ray irr adiation itself and the enhancing effect of radiation on urethan-induc ed tumorigenesis are scarcely influenced by immunosurveillance mechani sms mediated by T cells.