444 BIOLOGICAL EFFECTS OF RADIATION 



limbs in this experiment. The effect of the irradiation seemed to be not 

 on cartilage tissue as such but on the initiation and differentiation of new 

 cartilage. It appeared that the critical period mentioned for the regener- 

 ating limbs might be identical for the period of cartilage initiation and 

 differentiation, or simply the expression of the sensitivity of cartilage 

 differentiation to X-rays. 



The " pseudoblastema " seemed fundamentally like the normal 

 blastema, although it consisted of a much smaller number of cells and 

 did not proceed to the normal differentiation (Fig. 16). Vacuolation 

 appeared among the widely scattered nuclei and there was a considerable 

 amount of intercellular material that was apparently nonliving, pre- 

 sumably the debris of broken-down cartilage matrix and of disintegrated 

 cells. As with the normals, it was impossible to distinguish between 

 cells of the pseudoblastema proper and cells released by dissolution of 

 the cartilage. In contrast with the limb of the normal regenerate, the 

 limb of the irradiate showed no normal mitoses. Instead there were 

 many abnormal mitoses with tangled masses of chromosomes in no very 

 definite orientation, in the manner that has long been known to result 

 from X-ray exposure. Other cellular abnormalities were increase in size 

 of nuclei as compared with those of the normal blastema; later, the 

 appearance in these swollen nuclei of deeply stained granules ; and finally, 

 remnants of such disintegrating nuclei in the intercellular debris. 



In discussing the foregoing observations and interpretations, Butler 

 points out that the irradiation in some manner inhibits differentiation 

 of the cells of the blastema. Whether the effect should be regarded as 

 acting directly upon the cells of the blastema, or as an indirect effect 

 resulting from some action of the rays upon the organism as a whole, he 

 leaves an open question. In any case the cells of the blastema are 

 particularly susceptible to the rays, as might be expected, since the nor- 

 mal blastema is a region composed of actively dividing cells. The 

 pseudoblastema shows only a limited number of vmdifferentiated cells and 

 no normal mitoses. The prevention of regeneration he regards as due 

 "to the activity of the X-rays in preventing cell division and more 

 particularly in preventing differentiation of the cells of the blastema 

 which normally give rise to the components of the regenerating limb." 

 The second effect, namely, the dissolution and final disappearance of the 

 cartilage, which he characterizes as like cartilage dedifferentiation "run 

 wild," he thinks may be associated with the effect of the rays upon 

 differentiating cells, that is, prevention of the differentiation of new 

 cartilage within the blastema may have brought about secondarily the 

 dedifferentiation of cartilage already formed. According to such an 

 hypothesis, "cartilage dedifferentiation does not occur in limbs in which 

 X-radiation prevents digit formation, for the reason that in the process of 

 normal digit formation dedifferentiation is not involved," and the 



