Damage and morbidity from pneumonitis after irradiation of partial volumes of mouse lung

Purpose: The aims of this study were to: (a) define the relationship of dose and volume irradiated to damage and morbidity in mouse lung; (b) determine the threshold volume for morbidity after partial lung irradiation; and (c) determine whether the response to radiation of mouse lung is independent of the region irradiated. Methods and Materials: C3Hf/Kam female mice were used in this study. The fractional volume of the lung to be irradiated was determined by two methods, weights and computed tomography (CT) scanning. Two experiments were performed to define the volume effect and to determine whether the response of the mouse lung to radiation was homogeneous. In the first experiment, single doses of x-rays ranging from 12 to 20 Gy were given to partial volumes of 84%, 70%, and 40% including the base, 50%, 33%, and 17% including the apex, to 43% in the middle, and to the sum of 57% as 17% in the apex and 40% in the base. In the second experiment, the same volumes of 50% and 70-75% in the apex and base of the lung were irradiated with single doses ranging from 12-19.25 Gy. Morbidity from radiation pneumonitis was quantitated by two end points, breathing rate and lethality between 12 and 32 weeks after irradiation. Damage was assessed by histophological evidence of pneumonitis. Results: Clear well-difined dose-response curves were obtained fro bot breathing rate and lethality after all volumes irradiated. There was a clear volume-dependent shift of the dose-reponse curves for breathing rate and lethality at 28 weeks after irradiation, the end of the pheumonitis phase of damage, to higher doses compared with these data after whole-lung irradiation. In addition, the slopes of teh dose-response curves for irradiation of partial lung volumes were more shallow compared to those after whole-lung irradiation. Increases in breathing rate correlated with lethality when the volume irradiated was equal to or greater than 50% of the reference volume. However, after irradiation of volumes smaller than 40%, breathing rate increases were not accompanied by death. A heterogeneous response of the mouse lung to radiation was observed in the first experiment and confirmed by the second experiment. For a given volume irradiated, the isoeffect dose was always less for the base than for the apex of the lung. The threshold volume for breathing rate changes was less than 17 and 40% when the irradiated volumes involved the apex and base, respectively. For lethality, the threshold volume was between 40 and 70% for the base and greater than 50% for the apex of the lung. Finally, damage as assessed by histological evidence of pneumonitis was observed in the irradiated area only. Conclusions: (a) The volume effect was resolve in mice, (b) the volume effect in mouse lung exhibits a clear threshold for morbidity, (c) the threshold volume for morbidity is dependent on the end point, (d) the response of mouse lung is heterogeneous, dependent on the site irradiated, and is always greater for the same volumes irradiated in the base than the apex, and, (e) histopathological damage does not always produce observable morbidity.