324 H. MAISIN 



DISCUSSION 



UPTON: Did the nucleotides affect recovery in the small intestine? 



MAISIN: We did not look at intestine but anyway nucleotides do not protect against 

 intestmal mortaUty only against bone-marrow mortality. 



drasil: We have studied the stimulation of regeneration in irradiated bone-marrow by 

 the application of deoxynucleotides. On the basis of in vitro experiments in which the 

 DNA synthesis of a single bone-marrow cell was studied we are coming to the conclusion 

 that the preciirsors of DNA are capable of stimulating or initiating the DNA synthesis 

 preferably in reticular cells. They are not capable of mcreasing the DNA synthesis in 

 heavily damaged cells of the "blast" type such as myeloblasts, erytln-oblasts and so on. 

 Since the reticular cells are normally either incapable of synthesis or the ability to synthe- 

 size deoxynucleotides is very low, the addition of deoxynucleotides into the medium 

 leads to increase in the DNA synthesis. But what is the mechanism? It seems that only 

 a very small proportion of added deoxynucleotides gets into the cells and it seems that 

 irradiated cells have a greater permeability for deoxynucleotides than non-irradiated 

 cells. 



ALEXANDER: I would just like to ask Dr. Drasil and Dr. Maisin whether they could sum- 

 marize for us their experience on the effects of givhig nucleic acids and nucleotides 

 afterwards on actual survival. There have been so many claims (winch other people have 

 not repeated) that the actual LD50 is affected, that I wondered whether they could sum- 

 marize for us their own views on whether any of these nucleotides of DNAs or RNAs have 

 any influence on the LD50. 



MAISIN: I tlunk we know that they are really active given afterwards; the dose reduction 

 factor is something like 1-1. 

 ALEXANDER: DNA or RNA? 



maisin: Both of them. It is a little bit better maybe with RNA nucleotides than with RNA 

 alone but for higher doses of radiation no, certainly not. 

 ALEXANDER: 1-1 must be fairly margmal. 



maisin: Yes, it is not very much; with mercaptoethylamrne given before irradiating we 

 got the same dose reduction factor. 



ALEXANDER: But a reduction factor of 1-1 can be obtained non -specifically by injectmg 

 almost any irritant or sometlihig that stimulates the haemopoietic system. 

 maisin: Anyway we always inject our irradiated controls with saUne without protecting 

 at all. When we combme RNA and marrow the dose reduction factor remams the same 

 if we compare the results obtained with those rats and marrow-injected rats alone. 

 cottier: I would like to ask how this RNA was prepared; I wonder if anybody has ever 

 used isogenic RNA? 



maisin: We use yeast RNA. Some have used isogenic RNA. The results were no better. 

 DRASIL: I should like to answer Dr. Alexander's question. Survival experiments after 

 treatment of irradiated mice by DNA precursors showed that the survival is higher, but 

 the results are very variable. There are uniform results so far as bone-marrow regenera- 

 tion is concerned but very variable results for survival. It often seems that the appUca- 

 tion of DNA precursors leads to premature exhaustion of bone-marrow, that for instance 

 when we complete the start of marrow regeneration in injected mice and in controls then 

 the regeneration of bone-marrow starts two or tliree days earlier in experimental animals, 

 but after several days it stops again. 



BACQ: After nradiation you have the DNA in the nucleus and the RNA in the cytoplasm 

 being hydrolysed by the enzymes RNAase and DNAase which are activated by irradia- 

 tion. The cell does not necessarily die, but it is flooded with nucleotides. Now what 



