GENETIC VARIATION IN THE ACUTE LETHAL RESPONSE OF FOUR INBRED MOUSE STRAINS TO WHOLE BODY X-IRRADIATION

Abstract

H E existence of geneticvariation in radiation sensitivity within a species has been T acknowledged since HENSHAW (1944) reported a difference in the acute lethal response of C3H and LAFl mice to X-radiation. Since that time, strain or genetic differences in the radiation response of small laboratory mammals have been indi-cated for the sterilization dose (LORENZ et al. 1947), susceptibility to leukemia in-duction (KIRSCHBAUM and MIXER 1947), changes in blood chemistry (KOHN 1951), hematopoietic response after spleen protection (KAPLAN and PAULI, 1952), changes in body and organ weight (GRAHN 1954a,b) and for the reduction of life expectancy (HENSHAW et al. 1947; EVANS 1948; SACHER 1950; GOWEN 1956). Although the single dose LDSO value is often used in radiobiological studies as an experimental end point, information concerning genetic variation in this value is inadequate. Strain differences in the L D ~ o following X-irradiation are known to exist in mice (LORENZ et al. 1952) and rats (KOHN 1951). RUGH (1953), reviewing several independent studies, indicated that the LDSO value in mice may vary from 400r to 650r of X-rays, depending upon the strain employed. This range of LD50 values is confounded, however, with differences in age a t exposure, radiation quality, and unaccountable environmental factors that certainly must vary among laboratories. No attempt has been made to quantify, in a single experimental effort, strain dif-ferences in acute lethality. Consequently, certain features such as age changes in sensitivity, dosage-mortality slopes and sex differenccs are known only in general terms. MATERIALS AND METHODS In order to describe quantitatively strain or genetic differences in radiation re-sponse, three separate inbred mouse strains and two sublines of a fourth strain were exposed to single whole-body doses of X-irradiation. In addition to data on strain differences of LDSO values, dosage-mortality slopes and sex effects, some information on age effects was obtained by deliberately employing a limited amount of variation in age a t time of exposure. To facilitate interlaboratory comparison, strains were chosen which have been used frequently in experimental radiobiology, cancer genetics and general mouse genetics. Inbred strains BALB/c, C3HJHe, C57BL/6 and sublines A/ Jax and A/He of the A strain were used in this study. All mice were bred and maintained by full-sib matings in this laboratory undei conditions of constant temperature and humidity. The data for each strain are composed of a series of 15 to 20 independent tests