SEQUELAE OF THE LD/50 X-RAY EXPOSURE OF THE PRE-IMPLANTATION MOUSE EMBRYO: DAYS 0.0 TO 5.0

¹ Radiological Research Laboratory, College of Physicians and Surgeons, Columbia University, New York, N. Y. 10032

1. Either x-rayed or control male mice had average weights in excess of the females at a comparable age. Pre-implantation mouse embryos, subjected to x-rays and surviving for 24 months, showed no gross adverse weight effects of the exposures. In some instances those with a radiation history were heavier, probably because they came from depleted litters which had more growing space within the uteri.

2. Whole blood counts indicated that mice x-irradiated in the pre-implantation stage tended to have slightly higher white cell counts and slightly lower red cell counts than their parallel controls. Otherwise any possible hematological damage appears to have been rectified.

3. There were no permanent skeletal effects on mice x-irradiated in utero during the pre-implantation stages of 0.0 to 5.0 days, as determined by radiographs of five selected bones and two skull measurements at 2 months of age.

4. Mice x-rayed at fertilization or at 5 days gestation showed almost as good survival as did the controls, but those x-rayed on days 1 , 2, 3 and 4 showed slightly reduced survivals.

5. Corneal opacities occur frequently in these mice. Their eyes appear to be anesthetized to the particulate material in the bedding. There appeared to be no direct relationship between corneal opacities and the development of cataracts. Many mice with corneal opacities at two months recovered normal corneas at a later date.

6. Mouse cataracts appear to arise as nuclear or cortical sclerosis of the lens, but those arising in the nuclear region appear to be in the majority. The ultimate cataract, regardless of its origin, appeared to be similar in its involvement.

7. At any test period the percentage incidence of cataracts among the survivors was always higher among those x-rayed in utero than among the parallel controls.

8. Variations in cataractogenesis existed between males and females similarly x-rayed, as had also been shown in the previous study with the uniform exposure of 100 r x-rays. There appeared to be a sex differential in cataractogenesis of x-ray origin.

9. The fact that cataracts appeared earlier and to a greater extent among the x-irradiated mice than among the controls suggests that x-rays may hasten the onset of the usual senile cataracts.

10. There appears to be a greater incidence of bilateral as opposed to unilateral cataracts, and this seems to be particularly true for the females. The incidence of cataracts in one eye leading to bilateral cataracts occurred more frequently in mice x-rayed at fertilization and in females x-rayed at 1.0 and 5.0 days gestation. Thus, there was no clear-cut evidence of uni-leading to bilateral cataract development except possibly among some potential females. The precursors of the two eyes of any mouse at these early stages presumably received the same degree of radiation insult.

11. Since this study is based entirely upon x-irradiation of the early mouse embryo from fertilization to 5 days gestation, and since it has been demonstrated that x-rays during this period do in fact increase the incidence of cataracts, it must be presumed that the damage is done to the precursors of the lens since lens development is not initiated until about 11 days gestation. It is suggested that the etiology of these radiation-induced cataracts may be through an interference with the developmental process, originating with damage to chromosomes insufficient to be lethal.