Radiation-Induced Changes in the Gastrointestinal Function of Mice and Their Prevention by Chemical Means

Abstract

Death of rodents during the first week after whole-body or abdominal exposure to 1 to 10,000 r is due mainly to small-bowel injury (1, 2). Among the events which precede death are the mitotic arrest of the crypt cells (1, 3), impairment of DNA synthesis (4, 5), intestinal weight loss (6, 7), alterations in gastrointestinal motility (8), and water and electrolyte imbalance (9, 10). These effects can be prevented, in part, by the administration of certain sulfhydryl compounds shortly before irradiation (11–15). Studies of the effect of radiation on the normal functions of the gastrointestinal tract, such as digestion and absorption, may provide further insight into the mechanism of injury and death from this cause. Morehouse and Searcy (16) observed that supralethal doses of radiation retard the absorption of dioleylpalmitin in rats. Carbohydrate absorption has also been found to be reduced after whole-body x-ray exposure (17, 18). The purpose of the present investigation was to evaluate the effect of different doses of radiation upon intestinal absorption in mice and to attempt to prevent any impairment by the preadministration of 2-mercaptoethylguanidine (MEG), the transguanylated form of S-(2-aminoethyl) thiuronium bromide hydrobromide (AET). Oleic acid and serum albumin were selected as test substances because the small intestine is the primary site of their absorption. Moreover, the absorption of oleic acid does not depend upon the presence of pancreatic enzymes. Methods Ten-week old male C57BL/6J mice2 between 18 and 25 gm. were confined in separate sectors of a rotating cylindrical Plexiglas container during whole-body x-irradiation. They were fasted3 for eighteen-hours before irradiation in the twenty-four-hour oleic add experiments, but in the albumin-absorption and the sequential oleic-add-absorption studies they were fasted for only one hour. Different groups of mice received either 175 mg./kg. intraperitoneally, by mouth, or 400 mg./kg. of MEG (1 mg./0.05 c.c.), or an equivalent volume of sham solution,4 ten and thirty minutes, respectively, before irradiation. MEG (þH 7.5) was prepared as described earlier (19). Since MEG is rapidly oxidized in mildly alkaline solutions to bis(2-guanidoethyl) disulfide (GED) (Fig. 1), it was administered within two or three hours of preparation. Irradiation was carried out with the following physical factors: 250 kvp, 30 ma, 0.25 mm. Cu and 1 mm. Al added filtration, 0.95 mm. Cu h.v.l., 74 cm. F.S.D. Dose rates as measured with a calibrated Victoreen ionization chamber immediately before and after each experimental run varied from 89 to 100 r per minute, including backscatter, on different days. Oleic-Acid and Serum-Albumin Absorption Studies: Mice were permitted free access to food for thirty hours following irradiation and were then fasted for twenty-four hours.