729 



Comment on papers 71 and 72 



That DNA is built up prior 1o cell division was inferred at that date (1939) when 

 the study, the result of which is communicated in paper 71, was initiated. A sup- 

 pression of DNA formation should thus lead to a mitoitic arrest, and vice ve^rsa 

 and a suppression of DNA formation under the effect of exposure to irradiation 

 should reflect itself in a depressed ^^p incorporation into the DNA molecules 

 formed in the tissue of rats studied (papers 71 and 72 and Euler and Hevesy, 

 1944). To determine a change of 1 per cent in the DNA content of a tissue with 

 cytochcmical methods, difficulties are encountered even today (in the meantime 

 great progress was made in this field). The tracer method is very suitable for 

 demonstrating small differences in the new-formation of DNA molecules. If during 

 the experiment in the non-exposed Jensen sarcoma 1 per cent of the DNA mole- 

 cules get labelled (thus newly formed) a formation of 0.96 per cent only in tlic 

 irradiated sarcoma (thus a difference of 0.04 per cent in the total DNA content) 

 will be easily detectable. That DNA is built up prior to cell division was first proved 

 by Howard and Pelc (1951). In Vicia faha which they investigated, the synthesis 

 was already found to be terminated 6 hr prior to the beginning of visible prophase. 

 They made use of the powerful autoradiographic method in their investigations. 



After inadiation with a Roentgen lay dose of 300 r or more, incorporation of ^-P 

 into the DNA of the Jensen-sarcoma of most of the few hundred investigated rats 

 (paper 71 and Euler and Hevesy, 1944) was found to be strongly diminished, 

 as well as incorporation into the normal organs of 250 partly growing and paitly 

 adult rats (72). The cells of the organs investigated were in different stages of the 

 mitotic cycle, and, correspondingh^ the results obtained indicate a resultant of 

 the effect of exposure to radiation on cells which were in different stages of the 

 division process. 



Holmes (1947, 1948) investigated the effect of irradiation with Rontgen rays 

 both on the incorporation of P^^ into DNA and RNA. These investigations brought 

 out as well, as did very numerous later studies, the blocking effect on ^^p incorpora- 

 tion into DNA, while incorporation of ^^P into RNA was found by Holmes to be 

 only slightly affected. The result arrived at in papers 71 and 72 and by Euler 

 and Hevesy (1944) that exposure to Roentgen rays diminished ^^p incorporation 

 to about half the value observed in controls, was substantiated by a great number 

 of investigations (as for example, by those of Pelc and Howard, 1955) publis- 

 hed in the course of the last fifteen years, not, however, a possible interpretation of 

 this effect. According to the latter, incorporation of '^P into DNA may be partly 

 due to additional formation of DNA molecules and partly to renewal of DNA 

 molecules already present. It was suggested that irradiation with Roentgen-rays 

 possibly interferes with the formation of additional DNA molecules but not 

 with their turnover. We know today that in the growing tissue the formation 

 of labelled DNA molecules takes place at least in most cases in connection with 

 mitotic processes only. This view was already put forward in the first investi- 

 gation in this field (paper 67) where it is stated: "The rate of renewal of the 

 nucleic acid molecules in the liver may be identical with the rate of new-for- 

 mation of livor cells" 



Irradiation with ionizing radiation can interfere with DNA formation in diffe- 

 rent ways. Cell destruction produced by irradiation will stop DNA synthesis. 



