The accelerated repopulation of a murine fibrosarcoma, FSa-ii, during the fractionated irradiation and the linear-quadratic model

Abstract

Radiation response of a spontaneous mouse fibrosarcoma, FSa-II, to various fractionated doses was studied in vivo together with single dose cell survival curves. Early generation isotransplants were used. Animals were C3Hf/Sed mice derived from our defined flora mouse colony. Lung colony and TD 50 assays were used to determine cell survival. Surviving fractions were determined following fractionated irradiations of 1.0 to 5.0 Gy each per fraction with interfractional time intervals of 4 hr. The α/β ratio based on fractionated irradiations was 8.8 Gy for aerobic FSa-II tumor cells and flexure dose was less than 1.3 Gy. Multiple fractions of 5.0 Gy each given with 4, 12, and 24 hr intervals showed an increase in survival with increasing interfractional time interval, suggesting a rapid repopulation of tumor cells between fractions; namely, cell doubling time was shortened between fractions after the first 5.0 Gy doses. These results indicated that tumor cell repopulation is a critical factor in the fractionated radiotherapy. Linear-quadratic model was fitted to single dose survival data. Single dose survival curve of aerobic FSa-II tumor cells following lung colony assays which allowed determination of minimal survival of approximately 3.0 × 10 −3 showed that α, β, and α/β ratios were 0.25 Gy −1, 0.048 Gy −2, and 8.47 Gy, respectively. Single dose survival curve of the same aerobic cells determined by both lung colony and TD 50 assays to a survival level of approximately 3.0 × 10 −6 demonstrated that α, β, and α/β ratios were 0.375, 0.0127, and 29.5, respectively. Similar determination for hypoxic FSa-II tumor cells showed that α, β values were smaller whereas the α/β ratio was much larger than for aerobic cells. The oxygen enhancement ratio calculated by the α/β ratios was greater than 3.0.