EFFECTS OF X-IRRADIATION OF MICE EXPOSED IN UTERO DURING DIFFERENT STAGES OF EMBRYOLOGICAL DEVELOPMENT ON DURATION OF MATURE LIFE

Abstract

1. Mature lifespans, 75 days of age to death, when the mice were exposed to irradiations at different stages of uterine development, showed reductions in mean longevity which were dependent on both x-ray dose and period of embryological cycle. The design for this study was factorial. There were five irradiation treatments, 0, 20, 80, 160 and 320 r, six embryological stages: untreated, 6½, 10½, 14½, 17½ and newborn (19½) days of uterine development, two sexes and nine mouse strains. Three of the inheritance groups were inbred strains and six were the reciprocal crosses of these strains. Efforts were made to obtain two mice for each cell of the design. However, some treatments were so severe that this was impossible. X-ray dosages of 160 and 320 r at embryological ages 6½, 10½ and 14½ days were too lethal to obtain the requisite number of progeny in these groups.2. Six hundred and forty-seven completed mouse lives were collected. Mature lifespan ranged downward from 1194 days for the males and 921 days for the females. Both of these long-lived individuals had been irradiated, the male with 160 r at 14½ days embryological development and the female with 80 r at 10½ days embryological development. The frequency distributions of lifespan were of several types for the different groups, depending on the treatments, strains or sexes of the individuals.3. In terms of changes in mature lifespan, sex differences in the mice resulted in marked differences in the mean days they survived. Considering the in utero treated mice, the average unirradiated females survived for only 69% of the mean male lifespan. This male-to-female difference cannot be attributed to irradiation effects but rather to the hazards which differentially affect the physiological processes which separate the lives of the sexes, chiefly those associated with reproduction. Adjusting for these effects shows that the average female life under irradiation still exhibits greater sensitivities to irradiation in utero. Considering the available data for the dosages taken separately, the 20 r females had 85% of the mean lifespan observed for the untreated females, the males 96.7% that of the untreated males. Like comparisons for the 80 r were 82 vs. 93; for the 160 r, 73 vs. 89 and for the 320 r, 30 vs. 43.4. Intrauterine irradiations, when limited to 20 to 80 r, reduced the female durations of life at all stages of embryological development more than they did those of the males.5. Variance analyses emphasized the importance of sex as a controlling element in adult survival when the mice are under pressure of reproduction.6. Genotypic differences, as measured by strain and as separate from sex, have little effect on subsequent mature lifespans when the irradiation is small in amount, 20 including 80 r, or when given at 6½ or 10½ days of embryological development. The amount of radiant energy absorbed becomes more important to mature life's duration when the dosages of radiation are larger, 160 including 320 r, or when the exposures occur in the latter half of pregnancy. The variance analyses support the significance of the differences on which the above conclusions were based.7. Genotype also interacts with both stage of embryological development when irradiation occurred and with the dosage of x-rays absorbed.8. Individually the embryological stages when the irradiations took place have but small percentage effects on mature lifespan, although they do have pronounced effects on survival in the juvenile stage. All changes in lifespan come as direct irradiation effect to the soma of the embryos, as caused by acute irradiation. Lifespan lowering comes largely in the 320 r treated embryos in the form of a threshold effect which then carries through to the adult as cryptic damage to appear later in life.