[Experimental studies on mechanisms and prevention of radiation pneumonitis]

Radiation pneumonitis are well recognized as complications of radiotherapy for the thoracic malignancies. However, the pathogenesis of radiation pneumonitis has been poorly understood and prevention of it has not been developed. In this study, to define the mechanisms of radiation pneumonitis biologically, we measured lipid peroxides, the activities of glutathione peroxidase (GSH pex.), leukotriene C4 and D4 (LTC4 and LTD4) in the irradiated lungs of mice. Eight weeks old female ICR mice were sacrificed at various time periods (immediately after to 5 days) following the 10 Gy whole-body irradiation with 60Co gamma rays. The lipid peroxides and the activities of GSH pex. increased immediately after the irradiation, but returned to the control level 1 hour after the irradiation. And then, the lipid peroxides also increased from 1 day after the irradiation, while the activities of GSH pex. decreased below the control level. LTC4 and LTD4 in the irradiated lungs of mice were also significantly higher than those of non-irradiated controls. Furthermore, we investigated effects of Coenzyme Q10 and Azelastine for the prevention of radiation pneumonitis. Lungs of ICR mice after 10 Gy whole-thorax irradiation treated with those drugs were compared with the control lungs pathologically. Intraperitoneal administration of those drugs decreased the damages for endothelium, such as vacuole formation and stripping off the basement membrane which were recognized by electron microscope. Based on these results, it was strongly suggested that initial damage of irradiated lungs might be induced by lipid peroxides and leukotrienes, and that Coenzyme Q10 and Azelastine could reduce radiation pneumonitis.