gi2 METABOLISM OF THE CANCER CELL 12 



cessation of growth as measured by turbidity increase. Incubation of the 15-1- 

 strain in the absence of thymine resuked in an increase in turbidity, considerable 

 enlargement of the cell in girth and length, a doubling of the RNA and a signifi- 

 cant increase in DNA before the death of the organisms. It was also found that 

 development of a thymine deficiency in other organisms also produces death of 

 the cell. When the thymineless mutant was incubated in the presence of uniformly 

 labeled glucose it was observed that RNA components were synthesized but that 

 DNA synthesis was reduced nearly to zero (Cohen and Earner, 1954, 1955; 

 Earner and Cohen, 1954, 1955, 1956; Cohen, 1956a). 



Eromouracil, a competitive antagonist for thymine in lactobacilli and E. coli is 

 incorporated into the nucleic acid fraction (Weygand and Wacker, 1952). Cohen 

 and associates also found that this antagonist partially replaced the thymine 

 requirement in the 15-1-- mutant, permitting some increase in the number of 

 viable cells and also DNA and RNA synthesis. The growth fell off markedly indi- 

 cating that the DNA that had incorporated the bromouracil was unsatisfactory for 

 the continued survival of this organism. Cohen has thus established a concept of 

 unbalanced growth wherein the cell is unable to survive because of the inability 

 to synthesize deoxyribonucleic acid. He furthermore has speculated that cytoplas- 

 mic synthesis might be inhibited without inhibition of nuclear synthesis. A block in 

 the biosynthesis of cytosine riboside, but not of the cytosine deoxyriboside, might 

 produce this condition. Eurton (1955) has reported that after infection of the host 

 cell with bacteriophage T-, there must be a synthesis of protein before the synthesis 

 of the phage DNA is initiated. When these proteins have been formed, the synthe- 

 sis of the DNA is independent of the further synthesis of proteins. 



Leuchtenberger et al. (1954) have made further studies on the relationships 

 between hereditary pitviitary dwarfism in mice and the formation of multiple DNA 

 classes. Dwarf mice with a recessive anterior pituitary hypoplasia lack the multiple 

 DNA classes that are present in the tissues of their normal litter males. Treatment 

 of these dwarfs with pituitary growth hormone completely restored the DNA 

 classes, establishing the anterior pituitary as a factor in the formation of these 

 classes. Further evidence has been obtained that there is a basic DNA content or 

 multiple thereof in normal human cells (Leuchtenberger et al., 1954a). Malignant 

 cells usvially lack this uniformity, which may be attributed to the mitotic processes. 

 Zamenhof (1956) has reviewed the relation of the transforming principle of 

 microorganisms to the problem of growth. This principle, which appears to 

 be DNA, may be readily inactivated by mutagenic agents such as ultraviolet 

 light, mustard compounds etc. Other agents which have carcinogenic and 

 some mutagenic properties are without effect on this principle, i.e., methyl- 

 cholanthrene, urethane, and azo dyes. Nucleic acid metabolism, as related to the 

 transformation to resistance or dependence in levikemia cells of the mouse, has 

 been extensively studied by Law (1954). Incubation of a homogeneous solution 

 of normal rat liver or sarcoma with RNA resulted in a transformation of this acid 

 into DNA. Heating for 15 minutes at 100 "C destroyed this reaction (Cruz Coke 

 et al., 1953). Apparently this observation has not been extended, nor has it received 

 further confirmation. 



Several important approaches to the synthesis and mobilization of DNA prior 



