Thermal enhancement of radiation-induced leg contracture

Early and late damage in the normal tissues of the legs of mice was compared following treatment with radiation alone or radiation followed immediately by hyperthermia. Hyperthermia was given by immersing the hind leg in a water bath at 43.0 degrees, 43.3 degrees, or 43.5 degrees C for 1 hr. Damage was assayed by measuring leg contracture at various intervals from 5 to 365 days after treatment. At 5 days after treatment, only hyperthermia-induced contracture was observed. At 10 and 20 days, contracture increased with radiation dose in heated legs, but little contracture had developed in mice treated with radiation alone. By 45 through 365 days, however, contracture correlated with radiation dose both in mice treated with radiation alone as well as in those treated with radiation and hyperthermia. The greatest differential in the slopes of the dose response curves, suggesting hyperthermic radiosensitization, was seen 20 days after treatment. Nevertheless, at 365 days, contracture was still significantly greater in the mice treated with radiation and hyperthermia (43.5 degrees bath) than in the irradiated controls. Thermal enhancement ratios (TERs) were calculated from LCD50 values (LCD50 = radiation dose that would give a stated level of leg contracture in 50% of the mice). For greater than or equal to 3 mm contracture, TERs were 4.1 to 7.9 at 30 days, depending on bath temperature, but only 1.1 to 1.5 at 365 days. For an isoeffect of greater than or equal to 7 mm contracture, TERs were 1.9 to 5.3 at 30 days, and 0.8 to 1.8 at 365 days. Thus, contracture was enhanced more at 20 to 30 days after treatment with radiation and hyperthermia than at 120 through 365 days. Radiation damage not only appeared earlier in mice treated with hyperthermia than in those treated with radiation alone, but after the highest temperature tested (43.5 degrees bath), contracture was greater from 5 through 365 days after treatment than in controls treated with radiation alone.