Modification by WR2721 of Acute and Chronic Effects of Radiation Injury to the Lung.
Annual rept. 1 Feb 84-31 Aug 85, Final rept. Sep 82-31 Aug 85,
DUKE UNIV MEDICAL CENTER DURHAM NC
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We used quantitative ultrastructural techniques to 1 study the effectiveness of WR27221 in protecting rat lung cells and tissues against radiation injury 2 test whether the protective effect of WR2721 could be enhanced by glucocorticoids. Four groups were studied control rats, rats in which the left lung was irradiated with a single dose of 3000 rads, radiated rats injects with a 400 mgkg intraperitoneal dose of WR2721 thirty minutes before radiation, and radiated rats which received both WR2721 and 12 weeks of glucocorticoid administration. We studied all four groups at 12, 26, and 52 weeks post-radiation. We conclude that after a single dose of 3000 rads, WR2721 provided no protection at 12 weeks, modest protection at 26 weeks and substantial protection at 52 week post-radiation. Addition of glucocorticoids significantly enhanced the protective effects of WR2721. These effects first became manifest only between 12 and 26 weeks i.e. after glucocorticoid therapy ended. The mechanism of these effects is not known but is possibly due to relative preservation of the ability of lung cells to interact with each other to i inhibit fibroblast proliferation and collagen synthesis or ii remodel fibrotic lung tissues.