544 



L. G. LAJTHA 



Fig. 3. Dose response curve for X-ray effects on the process of DNA synthesis 

 (S period). Solid line: human bone marrow cells in vitro (formate-C 14 uptake). 83 Si 

 and S 2 : slopes of the two main components of the curve. Dotted line: rat thymus in 

 vivo (P 32 uptake). 84 (Note that for the thymus experiment the dose scale at any point 

 is '5 of that for human bone marrow.) 



The results in hone marrow cells indicated that even after 2000-5000 r. 

 in vitro, DNA synthesis proceeds in cells which at the time of irradiation 

 were in the process of synthesis (S period) hut at approximately half the 

 normal rate. The shallow slope of the curve after 2000 r. perhaps explains 

 the curious 50% inhibition found by so many workers. It was concluded 

 from these observations that the rate of DNA synthesis (defined as rate of 

 precursor uptake during the S period) depends on at least two factors: Si 

 and S 2 . Of these factors, Si is obviously much more radiosensitive than S2 

 (the 37% dose being 500 r. for Si and 13,000 r. for S 2 in hone marrow cells 

 in vitro). In the cells so far investigated the Si factor is responsible for about 

 50 % of the rate of synthesis, consequently if it is eliminated by radiation, 

 a 50% depression in precursor uptake — as usually found — would be ex- 

 pected. There may be cell types, however, in which the Si factor is responsi- 

 ble for a smaller or larger share in the rate of DNA synthesis; consequently, 

 the more resistant S2 curve may start at a 15 or 75% depression. 83 



Obviously the Si and S 2 factors are, at present, mere postulates. So far, 

 investigations on the relative biological efficiency of X-rays and a-particles 

 indicate an S 2 "vulnerable volume" (under these conditions a better term 

 than "target") rather similar to the DNA molecule, and the S 2 effect indeed 

 may be the result of direct gradual destruction of the DNA matrix by in- 

 creasing doses of radiation. 83 As to the nature of the Si factor, it is very 

 tempting to correlate it with the radiosensitive triphosphorylation proc- 

 ess. 82 ' 84 



