Radiation sensitivity in diabetes: preliminary studies with the alloxan diabetic rat.

Abstract

An often noted but little documented clinical impression is that diabetic patients are less able to tolerate radiation than the nondiabetic. The authors have encountered this intolerance particularly in those patients requiring radium or external pelvic radiation treatment for gynecologic cancer. The phenomenon is quite consistent and is not the result of technical error or patient selection. The literature contains instances of exaggerated radiation sensitivity in the diabetic animal exposed to total-body irradiation (2) but does not, to our knowledge, describe any local irradiation experiments in the diabetic animal. The present study is an initial effort to determine whether or not there may be an experimental correlation in animals for the effects observed in man. Experimental Method A. Diabetes Induction: Alloxan, a component of the uric acid molecule, administered subcutaneously or intravenously in the rabbit or rat, selectively destroys the beta cells of the pancreatic islets, inducing a variety of severe brittle or chronic diabetes which has been well studied physiologically (1,2). It is the most commonly used agent for inducing diabetes in animals. In our method of subcutaneous administration the injection of alloxan is preceded by two days of starvation. This insures a high incidence of diabetes with relatively benign permanent hyperglycemia. Fifty-two Fischer male rats averaging four months of age and 135 grams in weight were employed in this experiment. Preliminary blood sugar measurements had established a normal range of fasting blood glucose for these rats of 90–160 mg per 100 ml. Two animals were neither injected nor irradiated, and 17 received radiation but not alloxan. Of the 33 njected with alloxan6 4 received 40 mg/kg intravenously through the tail vein and 29 received 200 mg/kg subcutaneously. In 30 of those injected diabetes developed, and 26 survived for the radiation study. The first twenty-four hours after alloxan administration is the critical period for the rat, and an average of 2 cc 5 per cent dextrose in water solution was given once in the first eight hours to promote survival in the initial pancreatic shock-like state. The hyperglycemic animals lose weight initially and subsequently gain, if at all, at a far slower pace than the controls. They exhibit polydipsia, polyuria, and polyphagia. Serial blood sugar determinations reveal values as high as 600 to 800 mg per 100 ml. The diabetic state, once established, is nonreversible and can be followed easily with Tes-tape6 urine-drop specimens as needed. B. Radiation: It was intended to approximate the fractionation used in clinical radiation therapy as nearly as practicable. Accordingly, total doses ranging from 1,000 to 7,000 R (skin) were given to the left thigh in 400 R increments over periods of one to six weeks.