40. RADIATION AND NUCLEIC ACID METABOLISM 529 



lation. In most organs (e.g. lymph nodes) it will be the transient (i.e. divid- 

 ing-differentiating) population which will be thus affected, leaving the long- 

 lived stroma reticulum cells behind. The result will be a decrease in nucleic 

 acid content of the organ (compatible with loss of cells), and a decreased 

 uptake of DNA label when measured by the specific activity of DNA (com- 

 patible with loss of dividing cells). Loss of small cells (e.g. small lympho- 

 cytes) may produce a disproportionately large loss of DNA content com- 

 pared with the decrease in the wet or dry weight of the organ. 



2. Population Shifts 



In certain cell populations significant shifts in distribution of cells may 

 occur, even before significant changes in absolute cell counts. In a bone 

 marrow sample for example, most of the cells belong to "late" differentiated 

 forms which are either totally or partially incapable of DNA synthesis and 

 division. The proportion of "early" precursor cells is relatively small, but 

 these are the very cells which multiply and synthesize DNA rapidly. 5 In- 

 hibition of mitosis will allow maturation of these early cells into late forms, 

 thus resulting in a population shift and, consequently, a decreased uptake 

 of DNA label as measured by specific activity determination, without, 

 however, significant change in the total DNA content of the population, or, 

 indeed in the number of cells. 



Apart from the shifts produced by mitotic inhibition, interphase cell 

 death may remove actively dividing cells, producing a decreased DNA 

 specific activity. As the death rate of the cells may be faster than their re- 

 moval rate from the tissue, decreased DNA specific activity may be found 

 without the total DNA content of the tissue being diminished, and, of 

 course, without any effect on the process of DNA synthesis in any surviving 

 cell. 



3. Cell Cycle Changes Due to Mitotic Delay 



It has been shown that DNA synthesis only occurs during part of inter- 

 phase. 6, 7 Consequently, in any population of cells the specific radioactivity 

 of DNA will depend on the proportion of cells synthesizing DNA at the 

 time of administration of label, and on the rate at which each cell synthe- 

 sizes DNA. Inhibition or delay of mitosis, even in an exponentially growing 

 population, may delay or inhibit the onset of the subsequent cell cycle, 

 thus decreasing the proportion of cells synthesizing DNA, without neces- 

 sarily affecting the process of DNA synthesis in any one cell. 2 



5 L. G. Lajtha, in "Kinetics of Cellular Proliferation" (F. Stohlman, ed.) p. 174. 

 Grune & Stratton, New York, 1959. 



6 A. Howard and S. R. Pelc, Heredity 6, Suppl., p. 261 (1953). 



7 L. G. Lajtha, R. Oliver, and F. Ellis, Brit. J. Cancer 8, 367 (1954). 



