110 S. S. COHEN 



development of cytoplasm in the absence of mitosis. However, in Hver cells 

 siicli cytoplasmic growth obviously camiot continue indefinitely or the cell 

 would burst. In the case of hver, differentiation has provided mechanisms 

 for the liberation or excretion of synthesized protein; nervous tissue has well- 

 developed mechanisms of turnover. Evidently, an mtegrated system of 

 multiplying nucleus and cytoplasm without such mechanisms cannot be 

 blocked selectively in the development of one component alone without the 

 development of pathology. 



Ultraviolet and X-irradiation are other tools which produce such selective 

 damage. A common effect of such treatment is the development of giant cells, 

 as nuclear syntheses are inhibited and cytoplasmic growth continues. In 

 many cases such inhibited cells wiU eventually grow and lyse or necrose. The 

 loss of the ability of such cells to multiply is what is commonly meant by 

 "death" as applied to irradiated cells, although much of the metabolism of 

 such cells may appear to continue normally for many hours. Although many 

 workers have demonstrated an inhibition of DNA synthesis following 

 irradiation of many tissues and cell types, it has been difficult to be certain 

 in most of these experiments that the effect on DNA synthesis is indeed the 

 primary effect of irradiation. As pointed out by Howard (1956), a primary 

 effect on some stage of protem development in mitosis might be expected to 

 inhibit DNA synthesis, which should occur prior to subsequent mitotic cycles. 

 Indeed, it has recently been reported (Deering and Setlow, 1957) that low 

 doses of ultraviolet (UV) hght prevent bacterial division without apparent 

 effect on DNA, RNA, and protein synthesis. A similar result has just been 

 obtamed after treatment of E. coli with nitrogen mustard (Harold, personal 

 communication). 



In a possibly related result, it is known that ultraviolet-irradiated (or 

 mustard-inactivated) bacteria, incapable of DNA synthesis, will s}Tithesize 

 DNA after infection by phage, and this suggests that the radiation-induced 

 lesion may be somewhere other than in host DNA. However, a number of 

 counterarguments could point to the fact that such irradiation lesions may 

 be repaired anyway, and that perhaps infection merely hastens this process; 

 or that if the lesion is in the DNA of the bacterial genome, thereby producing 

 a block in the use of the template for synthesis, infection merely replaces the 

 damaged host genome by undamaged phage DNA, Indeed, the latter hypo- 

 thesis is supported by a great deal of evidence, of which the most interesting 

 derive from the lethal effects of radiation on DNA viruses. The damaged 

 DNA of a UV-irradiated phage may be repaired within the host bacterium 

 by photoreactivation of the host-virus complex, or may be replaced by 

 undamaged phage DNA in ceUs uifected with a multipHcity of virus particles. 



Although limited irradiation damage of cells produces a marked inhibitory 

 effect on DNA synthesis to a greater extent than on RNA or protein synthesis 



