40. RADIATION AND NUCLEIC ACID METABOLISM 541 



reported an inhibition of uptake of formate-C 14 and glycine-C 14 into DNA 

 2 hours after 2000-5000 r., but the same doses left adenine-C 14 uptake un- 

 affected. 66 ' 67 The obvious criticism of their experimental conditions is that 

 it is unlikely that chick embryo cells are "happy" in saline; a fact suggested 

 by the rather poorer uptake of precursors than would be expected under 

 normal growth conditions. This is also signified by the experiments on chick 

 embryos in vivo where much smaller doses of radiation (400-450 r.) pro- 

 duced an approximately 50% depression in uptake of both formate-C 14 and 

 cytidine-C 14 into DNA. 68 



Similar experiments performed on human bone marrow cells in vitro in a 

 more physiological medium indicated the same degree of depression of up- 

 take of both formate-C 14 and adenine-C 14 after 1000 r. 69 In these experiments 

 careful consideration was given to the behavior of cells in vivo as compared 

 with that in vitro, and indeed comparable doses delivered to the sternum 

 in vivo gave the same depression of formate-C 14 uptake as that found after 

 irradiation in vitro. 1 ® 



This apparent controversy could, perhaps, be explained on the basis of 

 differences in local pool sizes. Obviously natural pools would be severely 

 altered in dying cells, such as cells in an unsuitable medium. The in vivo 

 findings are more difficult to explain but Nygaard and Potter have shown 

 that relative pools for thymidine-C 14 are greatly different in the thymus, 

 intestine, or spleen — the specific activities of DNA being 2, 4, and 10 times, 

 respectively, that of the liver. 28 With P 32 , however, the thymus shows at 

 least 6 times the specific activity of liver DNA, even in a young animal with 

 a growing liver, 41 and obviously more than that in the older animals used 

 by Nygaard and Potter. These observations indicate that DNA precursor 

 pools may vary not only from organ to organ, but also that the relative 

 pools for individual precursors may be different in the same organ. 



These local pools may vary in different strains of animals under different 

 laboratory conditions, and until they can be measured with reasonable ac- 

 curacy, differential incorporation studies, and even more, studies of differ- 

 ential radiation effects, are highly inaccurate. At present there is no con- 

 vincing evidence that radiation acts on any particular step in DNA 

 biosynthesis. On the other hand, as will be discussed in the next section, 

 radiation may interfere with certain basic processes which, under certain 

 conditions, may affect different metabolic functions to different degrees. 



66 J. V. Passonneau and J. R. Totter, Radiation Research 1, 557 (1954). 



67 J. V. Passonneau and J. R. Totter, Radiation Research 3, 304 (1955). 



68 P. S. Lavik and G. W. Buckaloo, Radiation Research 1, 221 (1954). 



69 L. G. Lajtha, Nature 180, 1048 (1957). 



70 L. G. Lajtha, R. Oliver, and F. Ellis, in "Advances in Radiobiology" (G. de Hev- 

 esy, A. G Forssberg, and J. D. Abbott, eds.), p. 54. Oliver & Boyd, Edinburgh, 

 1957. 



