Early and Late Pulmonary Toxicity in Mice Evaluated 180 and 420 Days Following Localized Lung Irradiation

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Abstract
The lungs of 2- to 3-mo.-old female C3H/HeJ and 6-mo.-old male LAF1 mice were locally irradiated with graded doses of radiation ranging from 900-1800 rad. The patterns of animal deaths for times up to 60 wk after irradiation were recorded. Over this period mice in all the irradiated groups continued to die. However, the onset of animal deaths was dose dependent such that lethality occurred earlier after the higher radiation doses. Whereas mice receiving large radiation doses started to die by 75-100 days post-treatment, few or no animal deaths occurred in those groups receiving the lowest doses until 200-300 days after irradiation. At 180 and 420 days postirradiation animal lethality dose-response curves were constructed; these were similar in shape (sigmoid), but at the later time the calculated LD50 values were .apprx. 300-400 rad lower than those determined using the 180-day post-treatment end point. Histological examination of the irradiated lungs indicated that the animal deaths occurring by 180 days were associated with radiation pneumonitis while the late deaths were associated with pulmonary fibrosis. The addition of the radiation sensitizer misonidazole prior to lung irradiation did not significantly enhance pulmonary toxicity at either end point.

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