Dose-rate dependence of lung damage after total body irradiation in mice

Idiopathic pneumonitis is a major cause of morbidity and mortality in patients with leukaemia undergoing total body irradiation (TBI) and bone marrow transplantation (BMT). The effect of variation in dose relate of TBI on the development of lethal and sublethal lung damage has been investigated in mice by measuring changes in carbon monoxide uptake. CBA mice were irradiated using a 60Co source at 0.02, 0.05, 0.1, 0.2, 0.5 and 1.0 Gy min -1 to a total dose of 15.5 Gy. A log-linear relationship between the severity of impairment of carbon monoxide uptake (Vco) and dose rate was found. Ventilatory requirement (ventilation rate/Vco) was raised 20 to 40 weeks after TBI at dose rates above 0.1 Gy min -1. Time of onset and extent of elevation of ventilatory requirement were also dose-rate dependent. The implications of these findings for clinical practice are discussed.