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Radiation-induced intestinal injury is a dose limiting factor in the treatment of pelvic, abdominal, and retroperitoneal malignancies with radiation therapy. In experimental models, radiation has been associated with increased intestinal prostaglandin activity and in clinical trials prostaglandin inhibitors have been demonstrated to improve the symptoms of acute radiation enteritis. This study was conducted to determine if the prostaglandin inhibitor indomethacin could prevent the morphologic changes of acute radiation induced intestinal injury. Twenty-four male rats received either parenteral indomethacin at doses of 0.5, 1.0, and 3.0 mg/kg per dose every 12 hours or saline from 24 hours pre-radiation exposure until sacrifice 48 hours later. Twenty-four control animals received identical drug dosages and anesthesia but no radiation. Radiation produced a decreased villus/crypt ratio and increased acute inflammation and degeneration. Indomethacin treated animals demonstrated significantly less polymorphonuclear leukocyte infiltration and decreased degeneration. Villus/crypt ratio was not affected by indomethacin.

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Quantitative dose response measurements of diethylnitrosamine-and dibenzylnitrosamineinduced DNA single-strand breaks plus alkali-labile bonds (SSB + ALB) (single-strand breaks, apurinic/apyrimidinic sites, and phosphotriesters) were performed on samples of 100,000 nuclei from Sprague-Dawley rats. Twenty-four hours after diethylnitrosamine injection, there were no SSB + ALB in brain (nontarget), SSB + ALB in kidney (target), and SSB + ALB in liver (target only after partial hepatectomy, tumor promoters, or chronic administration). Seven days after diethylnitrosamine injection, liver SSB + ALB had declined. The noncarcinogenic diethylnitrosamine analog, dibenzylnitrosamine, induced no SSB + ALB at 6 hours or 7 days postinjection. Induction of DNA damage, therefore, correlates well with target organ specificity of tumorigenesis when specificity is broadened to include those organs that exhibit tumors only when DNA damage is followed by additional treatments.