RADIOPROTECTION OF THE RAT SMALL-INTESTINE WITH TOPICAL WR-2721

Background. The classic radioprotectant WR-2721 has been shown to redu ce the severity of small bowel injury when administered systemically s hortly before irradiation is delivered. This study tested the possibil ity that WR-2721 could provide protection when applied topically to in testinal mucosa. The second question addressed was the influence of pH on the effectiveness of this agent. Methods. The model used involved irradiation of exteriorized rat small bowel. A length of intestine was compartmentalized. The various individual segments were filled with a lumenal Tris buffer (pH 9), WR-2721, or a combination of these two, t hen irradiated with 1100 cGy. The animals were sacrificed 5 days later . Surviving crypt cells and mucosal height were the criteria used to q uantitate mucosal injury. Results. The pH 9 buffer alone provided a sm all (l6%) but significant preservation of crypt cell numbers. WR-2721 improved crypt survival by 54% at neutral pH, 83% at pH 9. Conclusions . These data indicate that WR-2721, when applied topically to the smal l bowel mucosa of the rat before irradiation, provides substantial pro tection against radiation damage. The degree of benefit is amplified g reatly when the drug is in an alkaline medium.