Influence of Radiation on DNA Metabolism 199 



lethal range has been related to alterations in the number 

 and type of cells present (Thomson et al., 1953). The instances 

 cited are only two of numerous experiments in which, as well 

 as the changes in DNA metabolism that were being studied, 

 alterations in the numbers and types of cells in the tissue were 

 clearly being produced by the irradiation at the same time. 



Radiosensitivity of DNA metabolism 



In some tissues (Holmes and Mee, 1955; Harrington and 

 Lavik, 1955) the efPect of 100 to 150 r in reducing DNA turn- 

 over can be clearly seen. While these doses are much lower 

 than those required to alter measurably many other processes 

 of cell metabolism, they are well above the minimum for 

 causing delays in the mitotic cycle. It is natural to ask 

 whether two so very radiosensitive effects may not be causally 

 related, and Hevesy many years ago suggested that cells may 

 be delayed by irradiation in entering mitosis because they 

 have been prevented from synthesizing their normal amount of 

 DNA. In several tissues, however, the synthesis of DNA 

 appears to be completed some time before prophase begins 

 (Howard and Pelc, 1953; Lajtha, Oliver and Ellis, 1954) and 

 it is not easy to see how stoppage of DNA synthesis can be 

 directly responsible for delay in cells already on the brink of 

 prophase, and containing their full double quantity of DNA. 

 There seems no doubt that these cells are sensitive to delay 

 since, in a great many tissues that have been studied, irradi- 

 ation is followed very quickly by a fall in the number of cells 

 entering mitosis. 



Hevesy also pointed out that the delay in mitosis caused by 

 irradiation would result in interference in DNA synthesis. 

 In 1945 he said: "Since the ionizing radiation blocks cell 

 division, it will influence the said cycle of changes [DNA 

 synthesis], and a reduction in the number of desoxyribose 

 nucleic acids built up during a given period of time can be 

 expected to take place." It seems important to examine the 

 implications of this statement in the light of knowledge of 

 DNA metabolism that has accumulated over the past ten 



