METABOLISM OF THE NUCLEIC ACIDS 415 



h. The effect of X -irradiation on the Uptake of Isotopes by the Nucleic Acids 

 of the Irradiated Tissue 



Hevesy^""^ has studied the uptake of P^^ by the DNA of Jensen rat 

 sarcoma after doses of X-rays of about 1000 r. and has shown that isotope 

 administered immediately after irradiation is taken up much more slowly 

 in the irradiated tumor than in non-irradiated controls. A similar degree of 

 inhibition (60 to 70 %) of DNA renewal was observed in normal rat liver, 

 spleen, and intestinal mucosa after irradiation. When the administration 

 of the labeled phosphorus was delayed until several days after exposure to 

 the X-rays, the difference between the specific activity of the DNA's in 

 the control and irradiated tumors was very much smaller than when the 

 isotope was given immediately after irradiation; indeed it was observed 

 in some experiments that 75% of the blocking effect of the X-rays dis- 

 appeared within 2 hr. of exposure to the radiation. The rapid diminution 

 in effectiveness of X-rays as a means of blocking DNA renewal may well 

 explain the greater sensitivity of growing tissues to irradiation, since, 

 in such tissues, the frequency of mitosis and the consequent synthesis of 

 DNA is much greater than in fully grown tissues where mitosis is relatively 

 rare. It follows that, if the effect of irradiation is only of short duration, 

 few cells would be damaged in adult or resting tissues, whereas many more 

 would be affected in a proliferating tissue. 



In weanling rat liver, the degree of blocking of P*^ uptake into the DNA 

 by X-irradiation immediately prior to administration of the isotope, is 

 similar to that found in adult animals. "^ When the animals were irradiated 

 continuously from the time of injection of isotopic phosphorus until sacri- 

 fice, the ratio of activity in the control and treated animals was found to 

 be as high as 11 to 1. 



Similar results on the inhibition of P^^ incorporation into the DNA of 

 rat Jensen sarcoma have been recorded by Holmes,"^'"* who has also ob- 

 served a lesser degree of inhibition of phosphorus uptake by the PNA of 

 the tumor. Inhibition of DNA synthesis in bean root has been observed 

 by Howard and Pelc* 



Hevesy,^""^ Holmes,^" '^^^"^ and Kelly and Jones"^ have noted an 

 indirect effect in an animal with an irradiated and a control tumor whereby 

 the uptake of P^^ by the control tumor was substantially reduced, although 

 to a lesser extent than in the irradiated tumor. In an endeavor to determine 



"1 G. C. Hevesy, Revs. Mod. Phys. 17, 102 (1945). 



112 G. C. Hevesy, /. Chem. Soc. 1951, 1618. 



"3 B. E. Holmes, Brit. J. Radiol. 20, 450 (1947). 



114 B. E. Holmes, Brit. J. Radiol. 25, 273 (1952). 



11* B. E. Holmes, Ciba Conf. on Isotopes in Biocheni., London p. 114 (1951). 



"« L. S. Kelly and H. B. Jones, Proc. Soc. Exptl. Biol. Med. 74, 493, (1950). 



