532 L. G. LAJTHA 



is given to mice in doses of 0.1 fxc. per gram body weight, then in a 20-gm. 

 mouse the total amounts to 2 fie, i.e. 5.6 X 10~ 3 /iM. The average diploid 

 cell of the mouse contains about 5 X 10~ 9 /jM thymidine in DNA; there- 

 fore, the administered dose of thymidine-H 3 is equivalent to the DNA thy- 

 midine content of about 10 6 cells — less than 1 mg. tissue in a 20-gm. mouse. 

 In most experiments where labels with low specific activity (1-10 mc//xM) 

 are used, the amount of material administered is usually large enough to 

 "swamp" natural pools. One is well advised, however, to take into consid- 

 eration instead of a general pool, individual organ pools, as there may be 

 great variations in this respect between different organs, and indeed be- 

 tween different cells of the same organ. 



It is evident from the points mentioned above — as also has been pointed 

 out by excellent previous reviews 2 - 3 ' 4 — that the whole concept of radio- 

 sensitivity of DNA synthesis needs critical reappraisal. In the following 

 sections evidence will be examined to establish whether it is legitimate to 

 speak of radiation effects on DNA synthesis, i.e. affecting DNA synthesis 

 while leaving other biochemical cell functions more or less intact. 



For the reasons mentioned above only such experiments will be included 

 in this survey where changes within one interphase were investigated. In 

 biochemical experiments (specific activity, DNA content) this means in- 

 vestigations not later than 4 hours after irradiation, in autoradiographic 

 work it may mean a time somewhat shorter than the total intermitotic 

 cycle, i.e. 12-20 hours, depending on the tissue investigated. 



III. Radiation Effects within One Interphase 



1. Effects in Tumors in Vivo 



In his pioneer work Hevesy has shown 10 ' ll - r -' that within about 2 hours 

 of irradiation P 32 uptake into DNA is depressed in the Jensen sarcoma of 

 the rat. This was confirmed by Holmes 13, 14 who also made the important 

 observation that Nembutal (which was used to sedate the animals during 

 irradiation) in itself is a powerful suppressor of P 32 incorporation into DNA 

 (and into RNA also), so much so, that it may mask the effects of radiation. 



The work was repeated and confirmed in several laboratories, using C 14 

 as well as P 32 as the label, in several types of solid tumors. 15 " 20 A particularly 



10 H. Euler and G. Hevesy, Kgl. Dansk Videnskab. Selskab 17, 1 (1942). 



11 H. Euler and G. Hevesy, Arkiv Kemi 17(30) (1944). 



12 L. AMstrom, H. Euler, and G. Hevesy, Arkiv Kemi 19, (1945). 



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

 " B. E. Holmes, Brit. J. Radiol. 22, 487 (1949). 



15 G. Hevesy, Nature 163, 869 (1949). 



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



17 H. Vermund, C. P. Barnum, R. A. Huseby, and K. W. Stenstrom, Cancer Research 

 13, 633 (1953). 



