CONTRIBUTIONS TO SURVIVAL MADE BY BODY CELLS OF GENETICALLY DIFFERENTIATED STRAINS OF MICE FOLLOWING X-IRRADIATIONS

¹ Department of Genetics, Iowa State College, Ames, Iowa

1. The influence of x-irradiation absorbed in three body regions and in the combinations of these regions has been measured by three subsequent responses: survival to radiation, natural resistance to disease and ability to acquire resistance following contact with the disease agent, S. typhimurium. The effects of irradiation are presented in this paper. Papers on natural and acquired resistance will follow. The experiment was designed as a factorial with five genetically differentiated strains of mice, S, Z, K, Q and Ba; four levels of radiation: 0 r, 320 r, 480 r and 640 r; eight treatment groups and two sexes. All mice were 46 ± 3 days of age when irradiated from a 250 pkv x-ray source operated at 30 ma with 0.25 mm. Cu + 1 mm. A1 filter at a dose rate averaging 170 r/minute. For the initial treatment the strains and sexes were well balanced, at least 50 mice in each of the 25 different treatment groups. The bodies of the mice were marked off in three regions, head h, mid m, and rear r, each comprising one-third of the body length. These regions, their combinations and their controls with each irradiation account for the 25 treatment groups. Shielding was done with -inch lead. As most deaths occur between 7 and 12 days, an interval of 15 days was allowed for expression of any direct effects due to radiation. Deaths were recorded daily.

2. Percentage survival and length of survival were the two measurements used for determining the reactions in each response.

3. The sexes responded in like manner to x-irradiation. A penetration or wave-length effect was indicated in these data. The reactions of the mice to the whole body irradiation at 250 pkv, 0.25 Cu + 1 Al filter 600 r were similar to those for 100 pkv, Coolidge tube, no filtration, 960 r.

4. Within the x-ray dose range used the responses of the strains to x-irradiation were shown to be partially genetically determined.

5. The levels of radiation resistance were in the order from resistant to sensitive: S, Z, Q, K and Ba. After 480 r total-body exposure the survival percentages of the five strains were: S, 79; Z, 75; Q, 66; K, 54 and Ba, 31. This order does not coincide with the order known to be followed in natural resistance to mouse typhoid: S, Z, K, Q and Ba.

6. Shielding of one-third of the body protected the mice of the five strains from 320 r and 480 r x-radiation, and to much lesser degree, depending upon regional exposures, from 640 r. The dose of 640 r was not of sufficient intensity to allow full expression of strain differences for the different regional exposures.

7. Whole-body exposure to 320 r reduced the 15-day survival for the more sensitive strains Ba and K, 480 r decreased survival in the five strains; 640 r was severe enough to largely overcome the genetic differences between the strains.

8. The mid region of the mouse was most sensitive of the three single regions, and more sensitive than the combined head and rear regions. The radiation effects were determined by the region rather than by the area of the body exposed.

9. The mid region in combination with the rear region showed greater sensitivity than the head-mid region. All strains were reduced in survival by exposure of the mid-rear to 640 r, whereas only the less resistant strains Ba and K showed the effects from the exposures of the less sensitive regions.

10. The decrease in survival showed the mid region as most sensitive for S, Z, K and Ba, followed by the rear portion with the anterior third of the body resistant. These four strains responded in the same manner but to different degrees.

11. The reactions of the Q strain separated it from the four other strains. Its level of radiation resistance with respect to the other strains was in contrast to its low level of natural resistance to mouse typhoid. Radiation resistance and natural resistance to this disease have been found highly correlated in seven of our strains of mice. The Q mice show comparable though slight sensitivity to x-radiation in the three body regions. Mortality in the Q strain was largely confined to whole-body exposures of 480 r and 640 r. This suggests that the Q mice have no particular center of radiation sensitivity, but that mortality is the result of the interactions of the cells throughout the body.

12. The data on length of survival confirmed the results from percentage survival and contributed additional information for those reactions that resulted in 0 or near 0 per cent survival.

13. The lead shielding, -inch in thickness, was adequate to protect the given regions from radiation. The three groups completely shielded when exposed to the three dosages of x-rays did not quite duplicate the 0 r group in their reactions. Mortality appeared unrelated to the x-ray dose, as 100 per cent survived 640 r, 98.4 per cent the 480 r and 99.6 per cent the 320 r.

14. The strains exhibited their own characteristic responses to different x-ray doses as was evidenced by the large values for dosage x strain interactions. These interactions were real, representing the expressions of genetic resistance and as such would contribute to the strain effects.

15. The effects of the relative sensitivities of the body regions were estimated quantitatively as well as qualitatively. The quantitative estimates compared favorably with the qualitative observations.

16. The additivity of the regional effects is supported by the little unaccounted for variation remaining after fitting the constants derived on the assumption that h, m, r and d were additive in effect.

17. Mortality from whole-body irradiation was only partially accounted for by the combined mortalities resulting from the exposures to the different regions of the body. The effect of total-body exposure over and beyond that of the combined regional effects, d, was interpreted as a measure of the reaction when all cells of the body of the mouse had been exposed, or when all recovery potential had been affected.

18. The whole-body effect, d, was large and suggested that all cells may contribute to recovery regardless of the organ or system involved. As a consequence, protection of any cells of the body during exposure to radiant energy may stimulate recovery.

19. In terms of host resistance the unexposed cells over-compensate. The extreme over-compensation initiated by cells in different unexposed regions when cells of other regions are inactivated points to the significance of all body cells in resistance whatever their degree of tissue or organ differentiation.

20. These results indicate that the body cells retained a totipotency to assist in maintaining the organism as a whole despite the differentiation which these cells may have undergone since their stem cells left the embryologically differentiating primitive tract. They further show the importance of maintaining at least a small portion of the body free from irradiation if irradiation exposure should occur through accident or calculated risk.