The long-term objective of this research is to improve the therapeutic advantage of radiation therapy to control cancer. In this project chronic radiation injury to small intestine--damage that frequently limits the dose in therapy of pelvic and abdominal tumors--is studied using a preclinical model in C3H mice. Radiation fibrosis that is the sequela of acute injury to the mucosal integrity will be distinguished from fibrotic or other quantifiable late effects of X-irradiation that are produced when multifractionation of the irradiation and protraction of treatment have enabled avoidance of the acute musocal defect and its sequela; and quantities descriptive of radiation responsiveness, such as alpha-beta ratios, and the thermal enhancement from radiosensitizing hyperthermia will be calculated with this distinction in mind. Tensile-testing techniques will enable collagen-related mechanical properties of the small intestine to be quantified at levels of tissue injury that are premorbid. Preparative surgery will immobilize a functional portion of the small intestine against the ventral peritoneal wall so that subsequently manipulation of the abdominal muscle through narrow gaps in special jigs will enable selective treatment of the attached portion of intestine without further surgery. Treatment will be with water-bath hyperthermia at 42 and 44 degrees C and with 250 kV X-irradiation. Anesthesia with etomidate will minimize pain and distress during treatment. Intestinal fibrosis will be quantified from the stiffness of the intestinal wall and the limits of its compliance. The effects of fractionation will be studied for treatment durations of 1, 4, and 7 weeks, with up to 70 X-ray fractions. Both fractionation and radiosensitizing hyperthermia will be studied with X-ray fractions down to 1-2 Gy. Risks attendant use of hyperthermia in retreatment will be quantified by both tensile testing and blood-flow (133-Xe clearance technique) measurements.
| Peck, J W; Gibbs, F A (1994) Mechanical assay of consequential and primary late radiation effects in murine small intestine: alpha/beta analysis. Radiat Res 138:272-81 |
