Influence of Radiation on DNA Metabolism 197 



depressed. Bennett and Krueckel (1955) have repeated this 

 experiment and observed a marked depressing effect of 

 irradiation on the incorporation of [8-i*C]adenine, the DNA 

 specific activity being less than half that of controls. No 

 explanation is apparent for the discrepancy between this 

 result and that of Harrington and Lavik. 



(2) Passonneau and Totter (1955) found no inhibition of 

 incorporation of [8-i*C]adenine into purines of DNA in 

 chick embryos in vitro. Doses were from 1,000 to 20,000 r of 

 gamma-rays. The incorporation of i*C-formate and ^*C- 

 glycine was reduced after doses of 5,000 r or more: 1,000 r had 

 a variable effect. The chick embryos, which were suspended in 

 saline for the two-hour period of the experiment, showed a 

 rate of DNA labelling with formate and glycine that was prob- 

 ably less than that expected from the increase in amount of 

 DNA in vivo in the same period. Embryos whose hearts had 

 stopped had the same performance as survivors of the 20,000 r 

 dose. Very large doses were required to have any clear effect 

 on DNA metabohsm, although Lavik and Buckaloo (1954) 

 found an approximately 50 per cent inhibition of ^^C-formate 

 or i*C-cytidine uptake into DNA of chick embryos after 

 400-450 r. These facts suggest that this experimental 

 system cannot be regarded as showing normal biosynthesis 

 of DNA. If they are accepted as doing so, it could be argued 

 that adenine is incorporated by exchange, since Brown (1950) 

 found that the renewal rates for both RNA and DNA were 

 higher with adenine than with ^sp or i^N-glycine. (Payne, 

 Kelly and Jones (1952), however, did not observe a higher 

 incorporation with [4:6-i4C]adenine than with i*C-formate, 

 [2-i*C]glycine, or ^ap). 



Taking all the evidence together, it appears that there is 

 no very clear indication that irradiation interferes with any 

 particular step in DNA synthesis. The blockage seems rather 

 to be a general one. This suggests that the inhibition of DNA 

 synthesis may not be a primary effect of radiation, but is the 

 result of blockage in some other event in the development of 

 the cell. 



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