40. RADIATION AND NUCLEIC ACID METABOLISM 543 



tion if the radiation is given 6 hours post heptatectomy (early Gi period). 73 

 Once the enzymes have been formed, however, irradiation with 1500 r. has 

 no effect. Apparently a process which normally results in the "triggering 

 off" of such kinases is destroyed or delayed by radiation. 



The question emerges: what is this radiosensitive process? In 1942 Mit- 

 chell reported an increase in ultraviolet absorbing material in the cytoplasm 

 of irradiated cells, 74 ' 75 an observation later confirmed by others. 76 This ob- 

 servation, on the face of it, only indicated that RNA synthesis, at least, 

 is not inhibited by radiation (later confirmed in tracer studies) and that 

 in irradiated cells RNA accumulated. Later, an increase in soluble deoxy- 

 polynucleotides 77 • 78 and soluble deoxyribonucleotides and ribonucleosides 79 

 was found in irradiated spleen, appendix, and thymus, which could have 

 been the result of either DNA breakdown or accumulation of precursor 

 compounds or both. However, the observation of Ord and Stocken, 80 that 

 there is an increase of deoxyribonucleoside triphosphates in irradiated thy- 

 mus (compounds very unlikely to result from DNA breakdown) gives a 

 strong indication that synthesis of DNA precursors goes on after irradia- 

 tion, and that "the inhibition of deoxyribonucleic acid synthesis after ir- 

 radiation is not due to lack of precursors but rather to failure of the poly- 

 merisation or to a breakdown in essential energy-generating mechanisms 

 in the nucleus." In search of such radiosensitive mechanisms Creasey and 

 Stocken found that the intranuclear phosphorylation of purine and pyrimi- 

 dine monophosphates to triphosphates 81 is a process which is completely 

 and immediately inhibited by 100 r. TBR and depressed by 50-80% even 

 after 25 r. 82 



At the same time an analysis has been made of the mechanism of radia- 

 tion effect on the process of DNA synthesis (S period). The dose response 

 curve on the rate of DNA synthesis during the process of synthesis gave a 

 poly phasic pattern both in human bone marrow cells in vitro** and in rat 

 thymus in vivo u (Fig. 3). 



73 F. J. Bollum, J. Anderegg, A. F. Brumm, and V. R. Potter, personal communica- 

 tion by Dr. V. R. Potter (1958). 



74 J. S. Mitchell, Brit. J. Exptl. Pathol. 23, 285, 296, 309 (1942). 



75 J. S. Mitchell, Brit. J. Radiol. 16, 339 (1943). 



76 M. L. Menten, E. T. Feldsted, and M. Willms, Exptl. Cell Research 7, 83 (1954). 



77 L. J. Cole and M. E. Ellis, Radiation Research 7, 508 (1957). 



78 R. K. Main, L. J. Cole, and M. E. Ellis, Nature 180, 1285 (1957). 



79 C. W. Bishop and J. N. Davidson, Brit. J. Radiol. 30, 367 (1957). 



80 M. G. Ord and L. A. Stocken, Biochim. et Biophys. Acta 29, 201 (1958). 



81 S. Osawa, V. G. Allfrey, and A. E. Mirsky, J. Gen. Physiol. 40, 491 (1957). 



82 W. A. Creasey and L. A. Stocken, Bioche?n. J. 69(2), 17P (1958). 



83 L. G. Lajtha, R. Oliver, R. Berry, and W. D. Noyes, Nature 182, 1788 (1958). 



84 M. G. Ord and L. A. Stocken, Nature 182, 1787 (1958). 



