Pathways of Radiobiological Damage 269 



Zirkle and Bloom and of the relations which have been 

 observed between survival and dose. 



The evidence in the case of Class (a) damage is equivocal. 

 Some of the experiments of Henshaw and Whiting were 

 expressly designed to reveal nuclear injury resulting from 

 ^-primary damage to the cytoplasm, but failed to do so even at 

 quite high dose levels. However, nuclear damage arising 

 from a transient disturbance in cytoplasmic metabolism or to 

 labile toxic products produced in the cytoplasm could have 

 escaped detection, despite the fact that eggs were fertilized 

 immediately after irradiation. 



Kaufmann, McDonald and Bernstein (1955) have observed 

 that doses of 250-1,000 r delivered to Drosophila larvae 

 salivary gland cells in vivo affect the colloidal properties of the 

 cells, and that doses of 1,000 r delivered in vitro affect the 

 stability of gels of calf thymus nuclei. Somewhat analogous 

 experiments have been made by Anderson (personal com- 

 munication). Kaufmann and co-workers show further that 

 nucleoprotein is damaged by doses (1,000 r) which are without 

 effect on either the DNA or the protein components when 

 irradiated separately. These experiments appear to have an 

 important bearing on Class (a) nuclear damage. They may also 

 provide the clue to the outstanding sensitivity of lymphocytes 

 and thymocytes since the lethal effects of radiation on these 

 two classes of cell bear certain resemblances to biological 

 effects known to proceed from Class (a) nuclear damage. 



The metabolic study of Class (b) nuclear damage, as induced 

 by ionizing radiations, appears to pose an extremely difficult 

 problem on account of the random nature of the primary 

 injuries. It would seem that there must be a period of time 

 during which a lethal injury is following hundreds of different 

 pathways in different cells. Mutations which ultimately prove 

 lethal may only be expressed a considerable time after irradi- 

 ation, either because the definitive mutation is delayed until 

 the time of gene reproduction or because nuclear control over 

 cellular metabolism is not immediate. During this interval of 

 time an opportunity is offered for the study of metabolic 



