KADIOACTIVE TKACERS 853 



gallons, for example those by Kelly, Hirsch, Beach and Payne, 

 (1955) carried out later, much extended these findings. 



One may ask why radioactive indicators had to be used to arrive at 

 the above-mentioned results. In the course of one hour the increase 

 in the mean DNA content of the Jensen-sarcoma of our rats amounted 

 to 0.75 per cent. If exposure should depress the rate of formation by 

 10 per cent the determination of this difference by the usual analytical 

 methods would necessitate the measurement of a change of 0.075 per 

 cent in the DNA content of the sarcoma. This is, even today, an almost 

 insurmountal)le task, although in the course of the 16 years which have 

 elapsed since the experiments were carried out great progress has been 

 made in the field of the analytical chemistry of nucleic acids. 



If we apply radioactive tracers the determination of a change in the 

 rate of formation of DNA becomes an easy task. We have now only 

 to take into consideration the 0.75 per cent of labelled DNA molecules, 

 and taking these to be 100, a depression in the radioactivity from 100 to 

 90 is quite easy to determine. 



If a popular comparison may be permitted, if we had to identify a 

 criminal by investigating the affairs of every inhabitant of this city, 

 this w^ould be an almost insurmountable task, which would be immensely 

 facilitated if Scotland Yard could restrict its investigations to persons 

 registered in its annals, thus to labelled ones. 



Calculation of the Amount of DNA Formed 



While it is quite easy to determine if and to what extent exposure 

 to irradiation influences incorporation of ^^p into DNA, and thus the 

 rate of formation of new DNA molecules, the quantitative determination 

 of the amount of DNA formed involves appreciable difficulties. The 

 calculation from radioactive data of the amount of DNA formed during 

 a time interval necessitates the knowledge of the precursor of the DNA 

 phosphorus and its specific activity. The simplest assumption to make 

 is that the administered radioactive phosphate penetrates into the tissue 

 cells, gets uniformly mixed with the orthophosphate present in these 

 and is then utilised in the synthesis of DNA. If 1 mgm of such phosphate 

 during the experiment has a mean activity of 100 relative units, and if 

 at the end of the experiment taking one hour, 1 mgm of DNA phosphorus 

 has the activity of one, then 1 per cent of the DNA molecules present 

 must have been built up in the course of one hour. 



Experience shows, however, that orthophosphate is far from being 

 always the precursor of the organic phosphorus compounds present in 

 the cell. In early investigations (Hevesy, Baranowski, Guthke, 

 OsTERN and Parnas, 1938) it was found, for example, that when adenyl- 

 phosphate is formed from adenosine in the presence of non-labelled 



