No abstract

Enhanced susceptibility to bacterial infection is one of the important changes which follow whole body exposure of mammals to moderate doses of ionizing radiation, Its occurrence during the post-irradiation period has been well documented by laboratory and clinical observation, but the time of its onset and duration has not been studied as systematically as it deserves.Schechmeister, Bond, and Swift (1) infected mice by inhalation of an aerosol of Streptococcus zooepidemicus at intervals after total body exposure to 350 r x-radiation.The ratios of the LDso's of normal mice to those of irradiated mice plotted against time showed that susceptibility to this air-borne infection increased steadily until the 15th day post-irradiation, then declined at the same rate to the 30th day, and slowly returned to normal by the 41st day.Kaplan, Speck, and Jawetz (2) related susceptibility to time post-irradiation (450 r) by plotting average day of death after intramuscular injection of a standard inoculure (100 LD~0) of a beta hemolytic streptococcus (strain C203). By these criteria, susceptibility of the mice was maximal between the 3rd and 7th day after x-radiation. However, Schechmeister, Paulissen, and Fishman (3) reported that they found susceptibility of mice to infection with Salmonella enteritidis inoculated intraperitoneally to be maximal 8 hours after irradiation with 350 r; but survival times were not reported, and it is well known that Salmonella enteritidis infection may not kill for a number of days after inoculation.In a small series of experiments, Marston et al. (4) found that susceptibility did not continue to increase beyond the 3rd day post-irradiation (475 r) among mice injected subcutaneously with a standard inoculum of a virulent strain of Proteus vulgaris (KfT).Hammond, Coiling, Cooper, and Miller (5) inoculated RAP female mice 9 to 10 weeks old, with approximately 107 Pseudomonas aeruginosa by stomach tube at different times (2 hours, 5 days, and 11 days) after whole body exposure to 550 r. Mor-*

No abstract

Bacterer-i~ of enteric origin has been found to occur in a high percentage of mice during the 2nd week following a single exposure to a moderate dose of ionizing radiation (1). This was demonstrated on 288 mice, of which 20 were killed for heart's blood culture each day following 600 r x-irradiation, and on 595 mice, of which 35 were killed and cultured each day after 450 r. The percentage of positive blood cultures was higher among the mice receiving the larger dose of x-ray, but in both series its maximum was reached during the period of greatest mortality. These results, however, merely indicated the presence or absence of bacteria in the circulating blood at the time of sacrifice. The next step toward an understanding of the pathogenesis of these spontaneous bacteremias was the determination of their time of onset and duration. Irradiated mice were accordingly subjected to a series of daily blood cultures. Materials and MetkodsMice.--lO week-old female Rockland "RAP" mice, weighing 20 to 25 gin. were used.They were segregated after irradiation and kept in individual jars to exclude direct contact as a source of cross-infection. Their bedding, which was changed once a week, was wood shavings which were sterilized by autoclaving and dried before use. They were fed on Rockland mouse pellets. Water was provided in sterilized water bottles and tubes which were changed daily. The mice were cultured in groups of convenient numbers (8 to 16).Irradiation.mEach of 7 groups of mice irradiated on different dates was exposed to a single dose of total body irradiation, carried out in the X-ray Division of the Argonne National Laboratory.* They received 550 r delivered at 250 kv., 15 ma., at a distance of 27 inches, using ram. copper and 3 ram. bakelite filters, at a rate of approximately 20 r per minute. During irradiation they were confined in perforated plastic tubes on a circular plate which rotated slowly within the irradiated field.

Previous studies have shown that the bacteremias which occur in mice during the 2nd week following a moderate dose (600 or 450 r) of total body x-irradiation are caused by members of their normal enteric flora (1). Of the enteric microorganisms, Pseudomonas a~uginosa was shown by serial blood cultures to be the most rapidly lethal once it had invaded the blood stream (2). These observations pointed to the intestinal tract as the site of origin of postirmdiafion bacteremias. They also suggested that Ps. aeruginosa might be a particularly suitablemicroorganism for measuring changes in susceptibility to infection. These indications were substantiated by the observation that Pseudomonas introduced by stomach tube into the gastrointestinal tract of irradiated mice gave rise within a very few days to a high incidence of fatal bacteremlas if inoculation had been made on the 5th or l l t h day post irradiation (3). In normal animals even larger numbers of the same strain of Pse~o-monas, inoculated by the same route, produced no ill effects. This striking difference between normal and irradiated animals in their response to oral inoculation with P s e u J~ seemed to warrant a study of the fate of this microorganism after its introduction into the gastrointestinal tract. Mice were accordingly inoculated on the 5th day post irradiation (550 r) with approximately l0 T Ps. aeruginosa and killed at daily intervals thereafter to determine the numbers of this microorganism in the small and large intestine. It was found that these bacteria were much more likely to become implanted and to multiply in the intestine, particularly in the small intestine, of the irradiated than of the normal mouse. This observation has led to a series of additional experiments undertaken in an attempt to explain this effect of irradiation.