Pathways of Radiobiological Damage 263 



the general level of metabolic activity {cf. the "cumulative 

 dose" concept developed by Lea (1946), Friedenwald and 

 Sigelman's (1953) treatment of mitotic delay in corneal epithel- 

 ium and Burns' (1954) treatment of division delay in yeast). 



Temporary arrest of cells about to enter division may be 

 caused by a great many agents, including hypoxia, depletion 

 of phosphate and glycogen. The possibility — indeed one may 

 even say the probability — must always be kept in mind that a 

 given result is achieved by different pathways under the 

 influence of chemical, u.v. and ionizing agents. 



In one or two materials the transfer of nuclei by microdissec- 

 tion procedures has been used to study the respective roles of 

 nuclear and cytoplasmic damage. Duryee (1949) studied the 

 incidence of nuclear pyknosis which develops in the course of a 

 few days at 22° C in salamander oocytes after exposure to 

 doses of around 3,000 rads. The oocytes were in early meiosis 

 at the time of irradiation. This form of damage appears 

 within half an hour if the dose to the oocytes is raised to 50,000 

 rads. When nuclei were isolated from the egg by microdis- 

 section and washed free of cytoplasm, this dose of radiation 

 produced negligible damage. Since in the intact egg this dose 

 did not produce immediate visible damage it is clear that even 

 after such relatively large doses metabolic processes must 

 intervene before the injury is apparent, and it is therefore not 

 unexpected that isolated nuclei appear unaffected. That the 

 nuclei have not been rendered insensitive by the microdis- 

 section was shown by the fact that the injury developed if 

 they were exposed to irradiation in the presence of cytoplasmic 

 brei, prepared by grinding in a mortar the contents of three 

 eggs from which the nuclei had been^removed. The brei could 

 either have provided conditions essential for the metabolism 

 of the nucleus or injured the nucleus indirectly through a 

 toxic product formed in the brei as a result of irradiation. 

 Evidence in support of the latter view was contributed by 

 microdissection experiments in which cytoplasm from irradi- 

 ated eggs (3,000 rads.) was transferred to unirradiated eggs 

 and resulted in nuclear pyknosis. The microdissection 



