Intracolonic WR 2721 protection of the rat colon from acute radiation injury

The radioprotective thiophosphate compound WR 2721, when given intraperitoneally, has been shown to effectively protect normal murine tissues, but not tumors, from radiation injury. Intravenous administration in humans has produced limiting nausea and vomiting at protective doses. The accessibility of the colon, coupled with the frequency of acute radiation injury to the rectum during pelvic irradiation, stimulated us to determine if WR 2721 was radioprotective when administered intracolonically. Double-blind histologic evaluation of colons from irradiated rats treated with intracolonic WR 2721 demonstrated a radioprotective effect with a dose modifying factor of 1.8 when compared with controls. A contact time of 30-60 min was optimal as was a WR 2721 dose of at least 15 mg. No systemic absorption was found. These data demonstrate that WR 2721 exerts its radioprotective effect without the coincident development of secondary tissue hypoxia and provide rationale for a clinical trial in humans.