GASTROINTESTIONAL MOTOR EFFECTS OF IONIZING RADIATION

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Radiation therapy is a major modality in the treatment of cancer. However, as the application and efficacy of this increased, so has the concern for normal tissue toxicity. For the treatment of abdominal and pelvic tumors, intestinal tolerance is often a major limiting factor. Recent studies from our lab (1, 17) and other laboratories (9, 10, 16, 18) have demonstrated that dramatic changes occur in the small intestinal motor activity following fractionated or single sub-lethal doses of ionizing radiation. Many of these changes may have a direct symptomatic relevance to patients receiving radiation therapy. the primary objectives of this research proposal, therefore, are 1) to expand our previous work on the effects of fractionated doses of irradiation on the small intestine to the colon, 2) to delineate the myogenic neural and chemical mechanisms that may be responsible for the changes in small intestinal motor activity after radiation, and 3) to extend the animal studies to the human model. In the canine model, the contractile and myoelectric recording will be made by using strain gauge transducer and bipolar electrodes, respectively. These devices will be implanted in the animal using sterile surgical techniques. The role of bile in the production of abnormal contractile patterns during radiation schedule will be studied by diverting the bile through exteriorized silastic catheters implanted in conscious state after a 10 day recovery period. The recordings from the human colon and small intestine will be made by manometric methods. The analysis of data will be done visually and by computer methods developed in our laboratory. Our ultimate aim is to delineate the mechanisms that produce abnormal motor patterns during radiation therapy in humans. The understanding for these mechanisms would help in proposing appropriate pharmacologic agents that may block these effects and improve human tolerance to radiation exposure.