The effects of anesthetics and misonidazole on the development of radiation-induced lung damage in mice.

The measurement of breathing frequency as a functional end-point of radiation-induced lung injury in mice allowed two phases of damage to be discerned; the first was manifest at 12-20 weeks after irradiation, the second beyond 28 weeks. Anesthesia by pentobarbitone sodium or steroids gave significant radioprotection of the lung during the early pneumonitic phase. Addition of the hypoxic cell sensitizer misonidazole removed the protective influence of the anesthetics but did not sensitize the lungs of unanesthetized mice. No anesthetic protection was detected for the late response, showing evidence for dissociation between early and late lung damage. The degree of epilation was measured on the dorsal thoracic region of the same mice. Protection by anesthetics and its reversal by misonidazole was also demonstrated. These results provide a warning of potential hazards in the laboratory evaluation of chemical radiosensitizers. The use of anesthetics at the time of irradiation could lead to an exaggerated enhancement of normal tissue damage.