158 SUMMATION BY CHAIRMAN 



200 r employed by us and others extirpate certain classes of primitive proliferative 

 and migratory cells and at a given stage produce specific deficits which are 

 translated by ensuing morphogenetic sequences into adult patterns of cortical and 

 other malformations. Dr. Brizzee's effects seem to be different and involve sub- 

 lethal alterations of the differentiating neurons and glia. He reports that the over 

 all cytoarchitectural pattern in the cortex is well organized in rats treated, say, 

 with 25 r successively on fetal days 10 to 17, yet there are significant cytologic 

 deviations from normal. These include alterations of the neuron, of the size 

 of the nucleus in relation to cytoplasm, and in how closely packed the cells are. 

 Some neurons were much too large. Closer packing of cells may have reflected 

 subnormal proliferation of dendrites or other deficiencies in fiber development. 

 What controls the size of a cortical neuron? How much influence do afferent 

 fibers have on determining cortical cell types, and what alterations in DNA and 

 RNA might lead to these cytologic abnormalities? Dr. Brizzee's further studies 

 on the morphogenetic sequences of events may tell. 



Dr. Sauer, extending the studies of the late Prof. F. S. Sauer on the nature of 

 the proliferative neuroepithelium, has come up with a new concept of partially 

 destructive injury to the nucleus of the radiosensitive primitive neural cells. We 

 had always thought that the quickly destructive effect of 200 r on the postmitotic 

 migratory and other sensitive cells was an all-or-none phenomenon. Histologic 

 studies of a series of embryos removed by Cesarean section at hourly or 2 hour 

 intervals up to 9 hours after exposure still confirms this for the most part, but 

 there is probably no discrepancy in our findings. In the chick, 200 r kills relatively 

 fewer cells than in the rat, and Dr. Sauer clearly showed that after this lesser 

 injury sublethal effects occurred. What happens to these partially incapacitated 

 cells? Do they grow up to be abnormal neurons like those in Dr. Brizzee's rats? 

 Some of his doses in rats may have produced effects corresponding to those 

 following 200 r in the chick. 



The malforming effect of radiation on the developing mammalian central 

 nervous system and retina depends on factors that include the stage of develop- 

 ment, the individual growth characteristics of the species, and the doses of radia- 

 tion. The dose largely determines what cells are killed and, therefore, what kind of 

 malformative sequences of growth will be set in motion. Considerable data are 

 now at hand on the morphology, the mechanisms, and the reproducibility of the 

 malformations induced in albino rats by 200 r of conventional 250 kv x-rays when 

 given at any stage from the 9th day of embryonic life to more than a week after 

 birth. The acute extirpative effect of this exposure seems to be chiefly limited to 

 the post-mitotic and primitive migratory neural cells, but obviously some chromo- 

 somal damage with delayed cell death must also occur. Figure 1 indicates in 

 schematic form how different doses kill cells in the young brain. The cerebral 

 vesicle of a 17 day fetal rat is represented and shows that the neuroepithelial zone 

 is a thick pseudostratified layer of tadpole-shaped cells which replicate their 

 chromosomes in the outer part of this zone and slide in to mitose in the lining. 

 This was demonstrated by F. C. Sauer in 1935 and confirmed by Watterson et al. 

 (1956), M. E. Sauer and Chittenden (1959), Sidman et al. (1959; Sidman, 1961), 

 and by Hicks et al. (1961a, b). Postmitotic cells are shaded, and they are the 



