Effect of hyperthermia given four hours after irradiation on late damage in mouse legs

The right hind legs of mice were treated with (1) radiation, (2) heat, or (3) radiation followed four hours later by heat. Leg contracture was measured at three, six and nine months after treatment and skin samples from the treated legs were excised for determination of hydroxyproline (i.e., collagen) and uronic acid content (i.e., ground substance) as a measure of fibrosis. The effect of pre-treatment administration of cobra venom factor (complement depletion) on these parameters was also tested. Following irradiation, considerable leg contracture, an increase in hydroxyproline content and a decrease in uronic acid concentration were observed. Following heat only, leg contracture, hydroxyproline and uronic acid content in skin were unaffected. When irradiation was followed four hours later by heat, leg contracture was delayed, reduced or enhanced compared to radiation only. In addition, collagen accumulation was delayed or unchanged by heat treatment, compared with radiation alone, without affecting the uronic acid content. Pre-irradiation administration of cobra venom factor (CVF) produced effects on leg contracture which were, in some cases, similar to those produced by heat treatment four hours after irradiation