EFFICACY OF RADIOPROTECTIVE AGENTS IN PREVENTING SMALL AND LARGE-BOWEL RADIATION-INJURY

PURPOSE: A variety of adjuvant treatments and cytoprotective agents ha ve been proposed to lessen the toxicity of radiation therapy. The foll owing study was designed to evaluate the benefit of six agents or comb inations using anastomotic bursting strength as a measure of transmura l radiation injury. METHODS: The 40-Gy study consisted of the followin g. Seventy-two male Sprague-Dawley rats were divided into eight equal groups: nonradiated control radiated untreated control and six radiate d treated groups. The radioprotective treatments included ribose-cyste ine (Rib-Cys), WR-2721, glutamine, vitamin E, MgCl2/adenosine triphosp hate, and RibCys/glutamine in combination. Radiated animals received 4 0 Gy to the abdomen. Two weeks after radiation, all animals underwent small bowel and colonic resection with primary anastomosis. Animals we re sacrificed one week postoperatively, at which time anastomoses were evaluated and bursting strengths determined. The 70-Gy study consiste d of the following. The same protocol was repeated for five groups of nine rats divided into nonradiated, radiated untreated, and three radi ated treated groups receiving RibCys (8 mmol/kg), RibCys (20 mmol/kg), and WR-2721. All radiated animals received 70-Gy doses. RESULTS: In t he 40-Gy group, there were 10 radiation-related deaths and 6 anastomot ic leaks among 70 rats studied. None of the differences between groups were significant. Nonradiated control group small bowel and large bow el anastomotic bursting pressures were significantly elevated compared with all radiated groups. Compared with radiated controls, there were significant improvements in small bowel bursting strength in the RibC ys, WR-2721, RibCys-glutamine, and vitamin. E groups and significant i mprovement in colonic bursting strength in MgCl2/adenosine triphosphat e, WR-2721, and RibCys groups. In the 70-Gy group, all nine nonradiate d control rats survived. Ah eight untreated radiated control rats died , four of eight WR-2721 animals died (P = 0.03), all RibCys (8 mmol/kg ) animals died (P = 0.03), and three of nine treated with RibCys (20 m mol/kg) survived (P = 0.08). CONCLUSIONS: WR-2721 and RibCys gave cons istent protection against large and small bowel radiation injury. The lower incidence of treatment-related toxicity and potentially equal or greater radioprotective effects may make RibCys more clinically usefu l than WR-2721.