Radiosensitivity of late recurrences following radiotherapy of murine fibrosarcomas

Abstract

Radiosensitivity of late recurrent tumors which emerged after radiotherapy was investigated. Tumors observed were fibrosarcomas. Recurrences emerged in the irradiated area approximately 200 days after a 50% tumor control dose of radiation of 60Co gamma rays or mixed irradiation with fast neutrons and gamma rays. The recurrent and radiation-induced tumors were differentiated by karyotype analysis. Once transplanted into fresh mice, the recurrent tumors grew more slowly than the original tumor. Tumorigenicity of the late recurrences was lower than that of the original tumor. Radiosensitivity of the late recurrences, which was examined using methods to assess control, tumor growth delay, and colony forming assays, was significantly higher than that of the original tumor. D0 values of hypoxic tumor cells were significantly smaller in two of the three recurrences compared to the original tumor. Oxic cells, when irradiated in vitro, also showed smaller D0 values for the recurrent tumors than the original tumor. Hypoxic cell fractions were between 0 and 14% in the late recurrences and 10% in the original tumor. These results are consistent with the hypothesis that radiotherapy causes mutation of tumor cells which results in increased radiosensitivity of surviving tumor cells.