PHOSPHATE IVIETABOLISM IN THE NUCLEUS 



L. A. 8T0CKEN 



Department of Biochemistry, University of Oxford^ England 



SUMMARY 



A brief at'c-uuiit is given of the effects of X-radiation on the biochemical events 

 in the mitotic cycle leading to the formation of nucleic acids. It is suggested that 

 low doses j^rodnce a disorganization of binding sites in the nucleus. Preliminary 

 data on the capacity of the nucleus to bind inorganic and organo -phosphates are 

 provided. 



This paper is a brief survey of what may be the salient biochemical 

 features associated with the synthesis of DNA in animal cells and an 

 attempt to see how far the derangement of DNA synthesis by X-radia- 

 tion can be explained in the light of our present knowledge. We our- 

 selves are convinced of the lack of basic information about the nucleus 

 and for this reason some of our recent findings which we have not yet 

 applied in the radiation field will be reported. 



The early work on the inhibition of precursor uptake into DNA is 

 due to Hevesy (1948). Most of these data were obtained at 2 hr after 

 irradiation and have been subjected to the criticism that by this time 

 changes in cell population or cell death have complicated the picture. 

 From our experiments (Ord and Stocken, 1957) with thymus gland, 

 however, it does seem that radiation produces its effect at once and 

 there is no further change until some considerable time afterwards. 



A second interesting observation due to Hevesy is the fact that once 

 the extent of inhibition has reached about 50 per cent a considerable 

 increase in the dose is required to produce much further change. We 

 followed up this point and correlated the dose with the inhibition of 32p 

 uptake into thymus DNA (Ord and Stocken, 1958). It seems clear from 

 these experiments that radiation has at least two separate functions. A 

 similar biphasic response has been found by Lajtha et al. (1958) when 

 bone-marrow cultures are irradiated. In order to explain the results it is 

 necessary to seek a sensitive as well as a rather resistant locus. 



The first clue to differential sensitivity of cells stemmed from the 

 work of Howard and Pelc (1953) on the radiation sensitivity of the 

 mitotic cycle in bean root tips. These authors showed that the cycle 



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