qiO METABOLISM OF THE CANCER CELL 12 



inhibited the incorporation of these labeled precvirsors into both purines and 

 pyrimidines of liver and only mildly inhibited their incorporation into the purines 

 and pyrimidines of hepatoma. These findings would indicate that alternative 

 biosynthetic pathways may be active in tumors. 



[iii) J\'ucleic acids and nucleoproteins . Many investigators have made comparisons of 

 the incorporation or uptake of labeled precursors into the nucleic acids of normal 

 or neoplastic tissues. Schmitz etal. (1954a) injected glucose- i-'^^C into rats bearing 

 Flexner-Jobling carcinoma. Within 1-5 h. there was considerable activity in the 

 RNA of the tumor while the liver RNA had little activity. The ^"^C of the tumor 

 RNA was found almost entirely in the ribose. DNA of the tumor was also active 

 within a few hours while the DNA of the liver did not contain any '"'C after this 

 same period. -^^P incorporation studies into the DNA and RNA of epithelioma 

 and of rat liver have been reported by Khouvine and Mortreuil (1954, 1954a). 

 The rate of uptake of labeled cell constituents into the cells of mouse ascites tu- 

 mors was as follows: inorganic ^^P, phosphatide, mitochondria, nuclei, plasma, 

 homogenate, nucleic acid and supernatant fluid in decreasing order (Lettre 

 et al., 1955). Inorganic ^^P and nucleotide components entered the nucleus very 

 rapidly. It is difficult to ascertain if structural units maintained their integrity as 

 they entered the ascites cells. The investigators suggested that these particles may 

 be utilized as structural units in the tumor. Amethopterin had no effect on ^^p 

 incorporation into phospholipids or nucleic acids of mouse leukemia or of normal 

 tissues, indicating that direct interference with nucleic acid formation is not asso- 

 ciated with the action of folic acid antagonists (Williams et al., 1954). 



Some interesting observations relative to nucleic acid biosynthesis in rapidly 

 growing tissue have been reported by Nygaard and Rusch (1955). The incorpo- 

 ration of ^^P into nucleic acids of regenerating rat liver was investigated. The 

 labeled phosphate was injected 20 h. after partial hepatectomy since it has been 

 previously observed that there was little evidence of nucleic acid formation as 

 measured by phosphorus incorporation during this period. Specific activity of 

 the acid soluble phosphorus fraction and the nuclear RNA were high within two h. 

 following administration of the labeled phosphate. At this same time interval the 

 activity of the DNA fraction was low. Approximately 24 h. following the injection 

 of the ^^P the specific activities of the acid soluble fraction and the nuclear RNA 

 had decreased and the DNA had increased so that all were approximately equal. 

 Several conclusions with respect to the role of nucleic acid metabolism in cellular 

 growth energed from these findings. The relatively long induction period between 

 hepatectomy and the initiation of nucleic acid synthesis would suggest that a 

 supply of precursors must be mobilized before actual nucleic acid synthesis or 

 cellular proliferation may proceed. Lettre et al. (1955) are also of the opinion that 

 stimulation of mitosis in the tumor cell is controlled by the supply of nucleic acid 

 building material. The findings of Nygaard and Rusch (1955) further confirm 

 the rapid incorporation of ^^P or other precursors into the nuclear RNA of prolif- 

 erating cells. The specific function of this nuclear RNA has not been established. 

 Balis (1956) studied the effects of regenerating liver on the synthesis of nucleic 

 acids in human tumor explants in the hamster. Labeled adenine or glycine was 



