Induction of lung tumors in C3H strain mice after single or fractionated irradiation with X-rays.

Murine model for lung tumor induction was studied in C3H/He male mice, a strain with low spontaneous incidence of lung tumors. Dose-response relationships in lung tumor induction were compared following irradiation with single doses and split doses of X-rays to the thorax either at night or in the daytime. The tumor incidence after a single 1.25 Gy dose at night during the period of nocturnal activity almost reached the maximum level after a 5 Gy dose in the daytime. Proliferative activity determined by observing the labeling index with tritiated thymidine in the normal lung was low as a whole, but tended to decrease in the daytime. When the proliferative response was induced by X-irradiation, significantly higher activity was observed at night. These circadian fluctuations were thought to affect radiosensitivity and lung tumor induction in mice. When split doses or fractionated doses of X-rays were applied to the thorax, lung tumor incidence definitely increased. The incidence after two 7.5 Gy doses with a 12 hr-interval was 41%, 3-fold higher than that after a single 15 Gy dose. Moreover, fractionated whole body irradiations (three times at 3 Gy with 3-month-interval) after a single 7.5 Gy thoracic irradiation was most effective in increasing not only the incidence (47%) but also the multiplicity of the lung tumor. More than 30% of tumor-bearing mice had two or more tumors following thoracic and whole body irradiations, while only 10% of tumor-bearers had multiple tumors after single or fractionated thoracic irradiation alone.