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Tumor induction in mice legs that were locally irradiated with carbon ions was compared to tumor induction by gamma rays after single and fractionated irradiation. A total of 250 tumors were induced in 1104 mice that received carbon-ion doses of 5 through 65 Gy. A total of 77 tumors were induced in 371 mice that received gamma-ray doses of 45 through 95 Gy. Of 91 carbon-ion induced tumors examined histologically, 97 percent were malignant, and sarcomas such as malignant fibrous histiocytoma (47%) and fibrosarcoma (32%) were most frequently observed. Malignant fibrous histiocytoma was also the most frequently observed tumor (12 out of 20 tumors; 60%) after gamma-ray irradiation, followed by carcinomas (25%) such as adenocarcinoma and squamous cell carcinoma. Neither dose fractionation nor linear energy transfer affected tumor induction for carbon ions and gamma rays. Dose responses were linear for carbon ions and gamma rays, and showed no saturation up to 65 Gy of carbon ions and 95 Gy of gamma rays. The relative biological effectiveness of carbon ions was 2.2 for tumor induction and 1.9 for early skin reaction. We conclude that risk of secondary tumor induction by carbon-ion radiotherapy would not be seriously higher than anticipated.

Tumor Induction in Mice Locally Irradiated with Carbon Ions: A Retrospective Analysis