Dose-limiting complications from upper half body irradiation in C3H mice

This investigation evaluates the usefulness of an experimental technique in mice that has been used to study lung tolerance as a major dose-limiting tissue in clinical radiotherapy. The pathological sequalae of upper half body irradiation using a range of single and fractionated (2 Gy per fraction once or twice daily) doses was characterized in C3H/HeJ mice. Four phases of potentially lethal syndromes were revealed starting with the very acute effects of oral inflammation within 1 month. Incisor damage occurred between 1 and 3 months when the supplying of powdered food appeared to prevent lethality from starvation. Single radiation doses then produced a predictable incidence of pneumonitis (3 to 6 months) followed by pleural effusions (6 to 12 months). These later two syndromes were absent in mice that survived the acute effects of fractionated UHBI. In accordance with other rapidly proliferating tissues, the estimated alpha/beta ratios for oral epithelial and incisor damage were notably larger than that previously reported for lung. This denotes the smaller capacity of the acute responding target cells to repair sublethal damage. The consequent predominance of acute reactions in the fractionated courses therefore confined the maximal tolerated dose to that which produced an unmeasurable level of pulmonary injury. Our discussion of these results warn against the simple extrapolation of fractionated or low dose rate UHBI lethality data from mouse to man without due consideration of extrapulmonary radiation effects.