INFLUENCE OF RADIATION ON 

 DNA METABOLISM 



Alma Howard 



British Empire Cancer Campaign Research Unit in Radiobiology , Mount Vernon 



Hospital, Northzvood 



Since the discovery by Hevesy and his colleagues (for 



references, see Hevesy, 1948) that the incorporation of ^^p 



into DNA of Jensen sarcoma and other tissues of the rat was 



markedly reduced by X-irradiation, it has been recognized 



that interference with DNA synthesis is one of the most 



general and important biological effects of radiation. It has 



been generally supposed that ionizing radiation interrupts the 



DNA biosynthetic chain by altering some reaction along its 



course, and it was natural therefore to examine the possibility 



that some step or steps in the biosynthesis would prove to be 



especially radiosensitive, and that the effects of irradiation 



might be altered by manipulation of the metabolites involved 



in such steps. Hevesy (1949) showed that the uptake of 



i*C-acetate into DNA of rat tissues was depressed by X-rays, 



as was that of ^^P. A number of papers since have indicated 



that a large part, perhaps the whole, of the biosynthetic 



process is affected by radiation. It has been claimed, however, 



that the incorporation of labelled adenine is not reduced by 



doses that have a marked effect on the entry of formate, 



glycine or orotic acid into DNA. This claim has been made 



from two sources : 



(1) Harrington and Lavik (1955) found that the incorpora- 

 tion of [8-i4C]adenine into DNA purines of rat thymus, during 

 the period 30 minutes to 24 hours after 100 r whole body 

 X-rays, was significantly greater than in controls. In the 

 same experiment the incorporation of [2-i*C]orotic acid 

 into DNA pyrimidines and of ^^C-formate into purines was 



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