THE NUCLEIC ACID CONTENT OF TISSUES AND CELLS 19 



V. Regenerating Tissues and Tissue Explants 



The regeneration of rat liver tissue that follows the removal of the median 

 and left lateral lobes (i.e., roughly two-thirds of the liver) is a truly hyper- 

 plastic process,"*' "^ the proliferation of new cells occurring at a rate "which 

 probably exceeds that of liver tumors. ^^" The restoration of liver tissue is 

 so vigorous that the remaining lobe has grown to reach 70 to 80 % of the 

 original liver weight within 4 to 10 days of the operation. i^' ^"- "* Regenera- 

 tion involves all the cell types found in liver, and after 21 days "the total 

 liver populations of parenchymal cells, sinusoidal lining cells and bile-duct 

 cells have all returned to normal."^" 



A number of authors, attracted by such an intensive proliferating system, 

 have investigated the changes in nucleic acid composition of regenerating 

 liver. Drabkin"^ noted that the percentage increments of DNA were closely 

 similar to the percentage weight increase during the restoration of rat liver. 

 Since then, the total DNA-P content has been recognized as a measure of 

 cell number, and important progress has been made.'^' ^"^ "*• ^^o ^s regards 

 the average amount of DNAP-P per nucleus during regeneration, there is 

 general agreement that this increases significantly during the phase of rapid 

 cell proliferation, although there is some doubt about the extent of the in- 

 crease in the first two days (Table VI). Price and Laird ^^ came to the con- 

 clusion that the PNA content of the small granular and the supernatant 

 fractions of the liver homogenates also doubled before cell division. 



There is a certain lack of agreement so far about the behavior of the 

 PNA-P/DNA-P ratio. All authors, however, agree that the PNA-P con- 

 tent per cell reaches the upper limit during the first four days of regenera- 

 tion, i^- "• ^"^^ most of the increase occurring in the small granule fraction. 

 These increases coincide with a period in which liver growth (by weight) is 

 most rapid, ^^^ in which cell number, as measured by cell counts, is nearly 

 doubled, "« and total DNA-P content is increased by 70 to 81 %.*^' "^ 



The PNA concentration per unit weight reaches its highest level between 

 l}/2 s-iid 6 days after partial hepatectomy,^^' ^*- ^*- ^^i^ 122 ^j^g increase occur- 

 ring in all the intracellular fractions. ^^ The significance of this can be judged 

 by the fact that Novikoff and Potter^^^ report no corresponding increases in 

 lactic acid, ATP, ADP, or the activity of some of the enzymes associated 

 with the tricarboxylic acid cycle during liver regeneration. 



lis G. M. Higgins and R. M. Anderson, Arch. Pathol. 12, 186 (1931). 



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



1'^ M. Abercrombie and R. D. Harkness, Proc. Roy. Soc. (London) B138, 544 (1951). 



118 G. T. Mills. J. Paul, and E. E. B. Smith, Biochem. J. 53, 245 (1953). 



lis D. L. Drabkin, /. Biol. Chem. 171, 395 (1947). 



120 J. E. Ultmann, E. Hirschberg, and A. Gellhorn, Cancer Research 13, 14 (1953). 



121 A. B. Novikoff and V. R. Potter, /. Biol. Chem. 173, 223 (1948). 

 12* P. Drochmans, Arch. biol. (Liege) 61, 475 (1950). 



