THE NUCLEIC ACID CONTENT OF TISSUES AND CELLS 31 



with 3'-Me-4-DAB. For the first 26 days the number of nuclei per liver 

 remained about 2000 X 10^ By the twenty-eighth day the number increased 

 nearly 50 %. The burst in proliferation involved a fall in the average cell 

 mass to nearly half that of the control liver cells; there was a corresponding 

 reduction in PNA and protein of the large granule fraction. 



Griffin et aiy^^ find a relatively small change in concentration of DNA-P 

 per unit weight during AAF carcinogenesis as compared with its large in- 

 crease in the precancerous tissue produced by 3'-Me-4-DAB. However, 

 there is a brief report that AAF fed to mice increased the liver DNA con- 

 centration by 22 % in 6 months, and by 236 % after 12 months. ^^^ 



Although the concentrations of PNA and protein in the whole tissue 

 are much the same for normal liver and hepatoma, the similarity conceals 

 an actual decrease in amount per cell and a redistribution within the intra- 

 cellular fractions. As the DNA per nucleus is unchanged in hepatoma cells 

 (see Chapter 19), it can be seen that the entire loss of PNA occurs in the 

 large and small granules, the absolute content per cell of the nuclear and 

 supernatant PNA remaining the same (Table IX^*^). 



The most potent carcinogen (3'-Me-4-DAB) causes the greatest reduc- 

 tions in the PNA content of the large and small granules, and the greatest 

 increase in the DNA concentration per unit fresh weight (Table IX^®"). 

 On feeding 2'-Me-4-DAB, which is noncarcinogenic, Striebach et aZ.^" re- 

 port a threefold increase in the number of mitochondria per cell and 

 slightly lower concentrations of PNA and DNA in the tissue. 



The PNA content of the nucleus is greatly increased in spleen cells of 

 mice carrying transplanted leukemia, but not to the same extent in mice 

 ^\ith spontaneous leukemia.^" In Ehrlich ascites tumor and in lym^phoma 

 cells, whatever the amount of DNA per nucleus, the PNA/DNA ratio is 

 always higher in tumor nuclei than in nuclei from healthy cells. ^^^ 



Although fasting produces a decrease in the PNA/DNA ratio in the 

 Flexner-Jobling carcinoma of rats, the tumor continues to grow at the ex- 

 pense of the tissues of the host.^^^ However, the rise in PNA/DNA in rat 

 liver tissue after administration intraperitoneally of 1,2,5,6-dibenzanthra- 

 cene, is not altered by restriction of dietary protein.^^^ The virulence of 

 mouse ascites tumor cells appears to decline as PNA is lost from the cells 

 during storage at 4°.^^^ 



Rerabek^^ and von Euler and Hahn^^ reported somewhat higher PNA/ 

 DNA ratios in the tissues of rats bearing Jensen sarcoma. The presence of 

 Crocker sarcoma 180 in mice increased the DNA concentration in liver by 



1" M. E. Lombardo and L. R. Cerecedo, Federation Proc. 12, 241 (1953). 



1" M. L. Peterman and R. M. Schneider, Cancer Research 11, 485 (1951). 



16B C. Leuchtenberger, G. Klein, and E. Klein, Cancer Research 12, 480 (1952). 



i«6 L. A. Elson, Symposia Soc. Exptl. Biol. 3, 327 (1949). 



1" E. Klein, N. B. Kurnick, and G. Klein, Exptl. Cell Research 1, 127 (1950). 



