Ill DNAandgrowth — MITOSIS 269 



There is no doubt that the evidence in favour of the view that transforming 

 agents are identical with genes is now exceedingly strong and that there is little 

 reason to doubt that the genes are DNA particles. Let us now go back to the cells 

 of more complex organisms and try to find out what happens to DNA during 

 mitosis. 



(d) DNA synthesis during mitosis 



We have already seen that DNA is a relatively stable substance metabolically 

 and that there is a tendency for a constancy of the DNA content per nucleus (or 

 rather per set of chromosomes). In view of the delicate mechanism of chromosome 

 and gene reduplication during mitosis, it is to be expected that the whole situation 

 will change considerably when a cell undergoes division. DNA must be synthe- 

 sized, in order to be equally divided into the two daughter cells, so that the DNA 

 content will obviously double at some point of the mitotic cycle. Furthermore, 

 DNA synthesis will occur at the expense of various precursors : if we add them to 

 the cells in a labelled form, we should find rapid incorporation in the newly 

 formed DNA molecules. Therefore, in dividing cells, we should expect to find 

 variations of the DNA content and a considerable increase in the incorporation 

 of various precursors into the DNA molecule. A large number of experiments 

 have definitely shown that both these expectations are actually fulfilled. 



Already the pioneer experiments of Hevesy and Ottesen (1943) and of Andreasen 

 and Ottesen (1945) have clearly shown that incorporation of ^-P into DNA is 

 much greater in actively dividing tissues, such as bone marrow and intestinal 

 mucosa, than in resting tissues. These early findings have been confirmed many 

 times, with greatly improved techniques. Very recently, for instance, Smellie et al. 

 (1955) found that DNA turnover, studied with ^^P, is faster in appendix and 

 bone marrow than in intestinal mucosa, spleen and thymus; on the contrary, 

 renewal of DNA is very small in kidney. As would be expected, if the incorporation 

 of ^^P into DNA is linked to synthesis during the mitosis, inhibition of incorpora- 

 tion by X-irradiation is greater in bone marrow and appendix than in thymus; 

 whereas in kidney, X-irradiation has little eflfect. 



Similar results have been obtained when precursors other than ^-P (for in- 

 stance formate, glycine or adenine) have been used; much experimental data 

 supporting this contention will be found in recent reviews by Brown and Roll 

 (1955) and by Leslie (1955). Particularly striking is the considerably increased 

 incorporation of all precursors into the DNA of regenerating liver [cf. Furst and 

 Brown, 1951) : such findings obviously mean that DNA synthesis is linked to the 

 process of mitosis. 



There is a general contention that DNA synthesis occurs prior to mitosis, i.e. 

 during interphase; however, the exact timing of this synthesis remains a subject 

 for hot discussion. While Lison and Pasteels (1951) found, by quantitative use 

 of the Feulgen reaction, that DNA synthesis occurs at the beginning of interphase. 

 Swift (1950) believes it to happen at the end of interphase. Walker and Yates 

 (1952) and Grundmann and Marquardt (1953) found DNA synthesis to occur 

 slowly and progressively during most of the interphase. 



In recent years, it seems that the workers who have studied DNA synthesis by 



Literature p. 2gg 



