NUCLEIC ACIDS AND NUCLEOPROTEINS 



911 



injected in these tumor bearing animals 24 h. after partial hepatectomy. The 

 uptake was increased almost threefold in the tumors of the operated animals. 



A most important contribution towards the mechanism of nucleic acid forma- 

 tion has been made by Ochoa and coworkers (Grvmberg-Manago et al., 1955; 

 Ochoa, 1956; Heppel et al., 1956). An enzyme isolated from the organism, Azoto- 

 bacter vinelandii catalyzes the synthesis of polyribonucleotides from 5'-nucleoside 

 diphosphates. This polynucleotide phosphorylase is widely distributed in micro- 

 organisms. Recently, Kornberg et al. (1956) have reported the formation of a thy- 

 midylic acid polynucleotide following incubation of E. coli extracts with ^''C- 

 thymidine and ATP. These observations do not, as yet, provide an explanation 

 for the mechanism of synthesis of the polydeoxyribonucleotide of the nucleus or 

 of the role of these structures in cellular division. The discovery of enzyme sys- 

 tems capable of catalyzing the synthesis of the polynucleotides provides a stimulus 

 for further studies in this area, and further elucidation of the mechanism of nucleic 

 acid biosynthetic pathways will undoubtedly appear in the near future. Whitfeld 

 (1954) has established a method whereby the sequence of nucleotides in un- 

 branched polyribonucleotides may be ascertained. 



Enzymatic depolymerization of deoxyribonucleoproteins by tumor cells has 

 been investigated by Kutscher and Eggers (1954). They concluded that the 

 nuclear enzymes, deoxyribonuclease, cathepsin, peptidases etc., are not involved in 

 mitosis, but are involved in other physiological functions. The rate of ribonuclease 

 activity was found by Maver and Greco ( 1 956) to be considerably higher in fractions 

 obtained from hepatomas than in corresponding fractions from normal rat liver. 



The virus studies of Cohen and associates (Cohen, 1955, 1956), while not 

 bearing directly on the cancer problem, may provide a basis for a more com- 

 plete understanding of malignant transformation and the growth of cancerous 

 cells. In studying the virus that infects E. coli it was found that this organism con- 

 tained 5-hydroxymethyl cytosine (HMC) in the DNA. This pyrimidine was not 

 found in the DNA of the host. A pathway for the conversion of cytosine in the host 

 DNA to the HMC of the T virus is presented in Fig. 6. 



CH2O 

 Cytosine ^ 5-hydroxymethyl cytosine 



+ NH, 



uracil 



NH3 

 CH,0 



+ NH, 



5-methylcytosine 



NH, 



+ NH, 



\} 



NH, 



5-hydroxymethyluraciI 



thymine 



Fig. 6. The biosynthesis of 5-hydroxymethylcytosine (after Cohen, 1955). 



The deoxyribosides of HMC or hydroxymethyluracil do not fulfill the pyrimidine 

 requirements in organisms requiring deoxyribosides of cytosine or of uracil. Thus 

 the hydroxymethylation appears irreversible. Cohen concluded that this type of 

 hydroxymethylation does not exist in normal cells. 



A thymine requiring mutant of E. coli, strain 15T-; was obtained by Cohen 

 and associates. This organism did not respond to the hydroxy derivatives mentioned 

 above. Exhaustion of thymine from the medium did not produce an abrupt 



Literature p. gig 



