go6 METABOLISM OF THE CANCER CELL 12 



tion the RNA value promptly returned to normal. The unshielded mice which 

 eventually develop a high incidence of thymus lymphosarcomas maintained high 

 thymic RNA values. The RNA per cell of a transplantable lymphosarcoma was 

 also found to be many times higher than the RNA of the thymus cell which served 

 as the control. This increase noted in the RNA per cell of lymphosarcoma does 

 not hold for all tumors when compared with their tissues of origin. Several tumors, 

 f.e. hepatoma, have a decreased cytoplasmic nuclear ratio relative to normal 

 tissues of origin and a net decrease in RNA expressed either on a content or con- 

 centration basis. The morphological characteristics of the cell have a direct 

 bearing upon the composition or metabolism of the cell and should be considered 

 whenever biochemical comparisions are made of normal and neoplastic tissues. 



Two DNA fractions were isolated from normal or cancerous tissues of the rat. 

 The fraction designated DNAj was precipitated by a 0.87% salt solution while 

 a second fraction, DNA, remained in solution. Rats bearing tumors were given 

 -^-P and the specific activities of the two DNA fractions from several normal 

 tissues, as well as the tumors, were measured. The DNAj, DNA2 ratio was higher 

 in the tumors than in the normal tissues (Backmann and Harbers, 1955). These 

 findings, if extended, may reveal that there are DNA components within the tumor 

 that may be more or less characteristic of the rapidly growing tissue. Evidence for 

 the heterogeneity of tissue DNA has been obtained by the chromatographic 

 fractionation on base-substituted cellulose anion exchange columns (Bendick et al., 

 1956). Butler et al. (1956) observed that DNA prepared from tumors of the rat and 

 mouse contained varying amounts of RNA. However, the same methods of 

 preparation in normal tissues give a DNA that was free of RNA. These investi- 

 gators suggested that the RNA of tumors may differ from that of normal tissues. 

 Some evidence was presented that tumor RNA preparations did have an ab- 

 normally high adenine and guanine content. 



A deoxyribonucleohistone has been isolated from transplantable mouse lym- 

 phosarcoma (Shack and Thompsett, 1953; Shack et al., 1953). Viscosity, solubility 

 and spectrophotometric titration behaviour indicated that the DNA component 

 exists in a macromolecular state. The degree of hydrogen bonding was the same 

 as was observed with DNA of calf thymus nucleohistone. 



[b) Metabolism 



In recent years a most intensive effort has been extended in the study of nucleic 

 acid metabolism in both normal and neoplastic tissues. A comprehensive review, 

 however, of all the findings in the important area would extend beyond the space 

 limitations of this chapter. The present status of purine and pyrimidine, nucleoside 

 and nucleotide biosynthetic pathways are adequately presented in the chapter 

 on intermediary metabolism (Chapter i). Also, the entire subject has been re- 

 viewed prior to 1954 by Reichard, Schlenk, Brown, Roll, Smellie, Hotchkiss, 

 Brachet and others in the two volume treatise on the nucleic acids (Ghargaff and 

 Davidson, 1955). The present review will be largely restricted to the more recent 

 findings concerned with nucleic acid metabolism in abnormal growth. An inform- 

 active chart compiled by Potter is presented in Fig. 5, in order to facilitate this 

 discussion. 



