NUCLEIC ACIDS IN CHROMOSOMES AND MITOTIC DIVISION 193 



cell cycle there must be a new formation of nucleic acids in amounts equal 

 to those in the mother nucleus (see also Chapter 19) ; secondly, these sub- 

 stances have to be distributed between the two daughter nuclei. 



Since the fundamental cytological studies of Flemming'"^ and Stras- 

 burger,'°^ it seems to have been generally believed that the new formation 

 of the chromosomal substances takes place in close relation to the process 

 of mitosis itself. This view, that most of the DNA of the chromosomes is 

 synthesized de novo at the beginning of each division, is still maintained by 

 many .^6, 107-109 



The attempts to analyze the new formation of the chromosomal nucleic 

 acids and its relationship to the cell cycle have involved principally two 

 different techniques. Quantitative analysis of the nucleic acid content of 

 single dividing cells, as well as of cells in bulk undergoing synchronous 

 divisions, has given information about the stage of the cell cycle during 

 which the main increase of the nuclear nucleic acids occurs. Secondly, iso- 

 tope tracers have been used to determine the time and magnitude of in- 

 corporation into the nucleic acids in relation to mitosis. 



Naturally occurring synchronous divisions suitable for macrochemical 

 analyses are rare but they can, however, be produced experimentally. After 

 partial hepatectomy in the rat, a sharp peak in the frequency of mitosis 

 occurs at 24 hours. As many as 10 % of the cells may undergo mitosis at the 

 same moment. It has been found that prior to the appearance of the mitotic 

 figures, the average DNA content of the hver nuclei had increased from 10 

 to 18 pg. per nucleus. 1^" The synthesis of DNA begins only a few hours 

 after partial hepatectomy"'-"^ and can be demonstrated by increasing 

 incorporation of labeled glycine into the nitrogenous bases of both DNA 

 and nuclear PNA."''-"^ 



Zeuthen et aZ.,"^-"^ using intermittent heat treatment of mass cultures 



°^ W. Flemming, Arch, mikroskop. Anal. u. Entwicklungsmech. 16, 302 (1879). 

 "6 E. Strasburger, "Zellbildung und Zellteilung." Jena, 1880. 

 0^ C. D. Darlington, Symposia Soc. Exptl. Biol. 1, 252 (1947). 



"8 M. J. D. White, "Animal Cytology and Evolution." Cambridge Univ. Press, New 

 York, 1948. 



09 C. D. Darlington and K. Mather, "The Elements of Genetics," Allen & Unwin, 

 London, 1949. 



10 J. M. Price and A. K. Laird, Cancer Research 10, 650 (1950). 



11 A. M. Brues, D. R. Drury, and M. C. Brues, Arch. Pathol. 22, 658 (1936). 



'2 A. M. Brues, M. M. Tracy, and W. E. Cohn, J. Biol. Chem. 155, 619 (1944). 



'3 H. B. Novikoff and V. R. Potter, J. Biol. Chem. 173, 233 (1948). 



'^ E. Hammarsten, in "Isotopes in Biochemistry" (J. N. Davidson, ed.), p. 203. 



Churchill, London, 1951. 

 IS N. A. Eliasson, E. Hammarsten, P. Reichard, S. E. G. Aqvist, B. Thorell, and G. 



Ehrensvard, Acta Chem. Scand. 5, 431 (1951). 

 •« E. Zeuthen, /. Embryol. and Exptl. Morphol. 1, 239 (1953). 

 1' O. Scherbaum and E. Zeuthen, Exptl. Cell. Research 6, 221 (1954), and personal 



communication. 



