Repair in the mouse lung during low dose-rate irradiation

The thorax of CBA mice was exposed to 60Co gamma-rays at dose rates ranging from 100 to 2 cGy/min. Iso-effect doses (ED50) were calculated for early and late lung damage from dose-response curves for breathing rate and lethality. A continuous increase in tolerance for early radiation pneumonitis was seen as the dose rate was reduced, reaching a dose recovery factor (DRF) of 2.6 at 2 cGy/min. There was significantly less dose sparing with 2 cGy/min for the rise in breathing rate during expression of late damage (DRF = 2.1). The lower DRF compared well with that obtained from late measurements of pleural fluid levels. Comparison with fractionation experiments indicated incomplete repair at 2 cGy/min with further dose recovery expected at even lower dose rates or at doses per fraction below 200 cGy. Since the dose-rate dependence of damage to haemopoietic tissue is less marked, this study predicts an advantage of employing low dose-rate total-body irradiation (TBI) in the treatment of bone-marrow transplant patients. A further gain in the therapeutic index may be expected using a hyperfractionated regime with small doses per fraction.