Carolyn W. Hammond

The effect of streptomycin therapy on mice irradiated with fast neutrons.

In a recent communication (1) it was shown that the mortality of mice after acute fast neutron irradiation was closely correlated in time with the development of generalized infection as demonstrated by the recovery of enteric bacteria from hearts blood and/or spleen. Such positive cultures were first obtained on the fourth day post-irradiation, coinciding with the onset of mortality. Between the fourth and the eighth days after exposure, the period of maximum mortality, approximately 40 % of the sacrificed mice showed positive cultures. It seemed to be established, therefore, that generalized infection, including invasion of the blood stream, occurred in mice after a single acute irradiation with fast neutrons. The present series of experiments was designed to determine the effect of streptomycin therapy on the mortality of neutron-irradiated mice in order to evaluate the importance of infection as a cause of death. Streptomycin was chosen because it had been found to be the most effective of the antibiotics used in the treatment of mice exposed to X-rays (2).

EFFECT OF CONTINUOUS GAMMA IRRADIATION OF MICE ON THEIR LEUKOCYTE COUNTS AND SUSCEPTIBILITY TO BACTERIAL INFECTION

CF-1 female mice 10 weeks old were exposed continuously to gamma - radiation at three dose levels: approximately 34, 72 to 67, and 130 to 127 r/day. Leukocyte counts and red cell volumes were followed, and at intervals susceptibility to bacterial infection was determined by intraperitoneal challenge with graded inocula of Pseudomonas aerugiosa. Increased susceptibility to this infection was related to the rate of irradiation rather than the total amount accumulated. At the lowest dose rate the accumulation of 2140 r during 9 weeks caused practically no increase in susceptibility to this experimental infection. At the next higher dose rate susceptibility began to increase after the third week. It was manifested principally by deaths among mice receiving smaller and smaller inocula of the test microorganism. At the highest dose rate used susceptibility increased more rapidly. The development of leukopenia and anemia was also related to the rate of irradiation rather than the total amount accumulated. (auth)

INCIDENCE OF ENDOGENOUS BACTERIAL INFECTION IN MURINE RADIATION CHIMERAS WITH SECONDARY DISEASE.

Pathological changes indicative of bacterial infection have been reported by several investigators in animals with secondary disease. Cultural methods were used in experiments to determine whether ...

Transient increase in resistance of mice to experimental infection following a small dose of x-radiation.

Summary CF-1 female mice, 9-10 weeks old, were exposed to a small dose of whole body X-radiation (50, 75, or 100 r) and together with unirradiated controls were challenged at various intervals by intraperitoneal injection of graded inocula of Pseudomonas aeruginosa. Comparison of the LD50s (30 days) of irradiated and control mice in each challenge showed a small but significant increase in resistance to the experimental infection during the 4th week following irradiation with 75 or 100 r. Exposure to 75 r was more effective than 100 r. The results suggest a possible explanation of “acquired radio-resistance.”

The Incidence of Endogenous Bacteremia in X-Irradiated Rabbits

In the mouse (1-5) and the rat (6-9) the development of generalized infection has been shown by a number of studies to play an important role as a cause of death during the second week after total-body exposure to moderate doses of ionizing radiation. Such infections, which are caused by microorganisms normally present in the gut, develop into overwhelming bacteremias, demonstrable by the recovery of large numbers of bacteria from the circulating blood. Although the guinea pig (7, 10) and the hamster (7) have not been as systematically studied, the available evidence suggests that in these species also bacteremia is a common finding in animals which die after irradiation. In the case of the dog, opinion is divided on the question of the importance of infection as a cause of death. Warren and Whipple (11), in an early study on irradiated dogs, regarded bacteremia as an agonal phenomenon. Howland (12) has concluded from a recent compilation of data on blood cultures that the occurrence of bacteremia bears no relationship to the survival or death of dogs exposed to 450 r. Among 30 dogs irradiated with 450 r, cultured for Dr. J. Garrott Allen (13), we found only 15 % of 88 blood cultures to be positive. Half of the dogs had been treated with aureomycin, but the incidence of positive cultures was the same as in the controls. On the other hand, Brecher and Cronkite (14) have observed such definite microscopic evidence of infection in the mouth, throat, and intestinal canal of irradiated dogs that they consider infection to play a definite role in the death of these animals. For a recent evaluation of the evidence regarding the importance of infection in the radiation syndrome, see Bond et al. (15). The apparent difference in occurrence of post-irradiation bacteremia in the mongrel dog and in the four species of rodents suggests a significant disparity in their ability to prevent the development of overwhelming sepsis. The dog not only belongs to another order taxonomically, but it is not customarily raised for laboratory use as are the rodents mentioned.In the mouse (1-5) and the rat (6-9) the development of generalized infection has been shown by a number of studies to play an important role as a cause of death during the second week after total-body exposure to moderate doses of ionizing radiation. Such infections, which are caused by microorganisms normally present in the gut, develop into overwhelming bacteremias, demonstrable by the recovery of large numbers of bacteria from the circulating blood. Although the guinea pig (7, 10) and the hamster (7) have not been as systematically studied, the available evidence suggests that in these species also bacteremia is a common finding in animals which die after irradiation. In the case of the dog, opinion is divided on the question of the importance of infection as a cause of death. Warren and Whipple (11), in an early study on irradiated dogs, regarded bacteremia as an agonal phenomenon. Howland (12) has concluded from a recent compilation of data on blood cultures that the occurrence of bacteremia bears no relationship to the survival or death of dogs exposed to 450 r. Among 30 dogs irradiated with 450 r, cultured for Dr. J. Garrott Allen (13), we found only 15 % of 88 blood cultures to be positive. Half of the dogs had been treated with aureomycin, but the incidence of positive cultures was the same as in the controls. On the other hand, Brecher and Cronkite (14) have observed such definite microscopic evidence of infection in the mouth, throat, and intestinal canal of irradiated dogs that they consider infection to play a definite role in the death of these animals. For a recent evaluation of the evidence regarding the importance of infection in the radiation syndrome, see Bond et al. (15). The apparent difference in occurrence of post-irradiation bacteremia in the mongrel dog and in the four species of rodents suggests a significant disparity in their ability to prevent the development of overwhelming sepsis. The dog not only belongs to another order taxonomically, but it is not customarily raised for laboratory use as are the rodents mentioned.

EFFECT OF DAILY EXPOSURE TO 15 r

Summary 1) CF-1 female mice were exposed to approximately 15 a day radiation for 9-15 weeks and challenged at intervals by intraperitoneal inoculation with graded doses of Pseudomonas aeruginosa. Comparison of LD50 of irradiated and control mice in each challenge showed that between 9th and 15th weeks a slight but demonstrable increase in susceptibility to experimental infection had occurred. 2) The increase caused by accumulation of 1350 r during 15 weeks exposure was, however, very much less than that resulting from a single acute exposure to 300 r X-radiation.

gamma

Summary 1. Nine to 10 weeks old female mice, averaging 27 g in weight were injected intraperitoneally with 0.2 mg (approximately 7 mg per kilo = LD90) of nitrogen mustard (Methyl bis (β-chloroethyl) hydrochloride). Cultures of hearts blood and spleen of mice sacrificed for that purpose were made at daily intervals. 2. Bacteremia was found to be present in over 1/3 of the mice on the 5th, 6th and 7th days. A number of additional mice on these days (6-17%) showed positive cultures of spleen only. The species of bacteria recovered from blood and or spleen were all members of the normal intestinal flora, with the exception of Corynebacterium pseudotuberculosis murium. 3. Generalized infection of enteric origin seems to play a less important role as a cause of death in mice poisoned with nitrogen mustard than in mice subjected to moderate doses of total body x-radiation.

RADIATION ON SUSCEPTIBILITY OF MICE TO EXPERIMENTAL INFECTION

Summary Intraperitoneal or intravenous injection of RNA or yeast autolysate before or after irradiation with 475 r reduced the mortality of mice from experimental infection with Pseudomonas aeruginosa initiated by intraperitoneal inoculation on the fifth day post-irradiation. Mortality was also reduced in unirradiated mice treated with RNA or yeast autolysate before inoculation with Ps. aeruginosa.

Occurrence of Generalized Infection of Enteric Origin in Mice Poisoned with Nitrogen Mustard.

Summary CF-1 female mice 4 weeks of age were exposed 6 days a week to 0.5, 1 or 2 r γ radiation/day. After 4 to 39 weeks exposure they were challenged by intraperitoneal inoculation of graded doses of Pseudomonas aeruginosa. No detectable effect on host resistance to this experimental bacterial infection was demonstrated. The authors express their grateful appreciation to the following members of Depts. of Medicine and Radiology, Univ. of Chicago: Dr. Leon O. Jacobson for use of the cobalt-60 room in Argonne Cancer Research Hosp. USAEC: Lawrence H. Lanzl for assistance in planning arrangements and for the dosimetric determinations; and George A. Sacher, Argonne Nat. Lab., Lemont, Ill. for many helpful suggestions.