158 A. X. BELOZERSKY AND A. S. SPIRIX 



cil, and 5-iodouracil. When bacteria are grown on a medium containing these pyrimi- 

 dine analogs, the latter are incorporated into the DNA instead of thymine. 95105 

 However, other analogs, e.g., 2-thiothymine, 92 ' "• l01 uracil, 101 5-nitrouracil, 99 ' 105 

 5-methylcytosine, 105 5-aminouracil, 92 ' " 5-ethyluracil," 2-thiouracil," and others, 

 are not incorporated, as such, into the DNA of bacteria, though they act as growth 

 inhibitors of the strains requiring thymine, presumably by competing with the thy- 

 mine uptake from the medium. In contrast, the incorporation of 5-bromouracil, 

 5-chlorouracil, and 5-iodouracil in the place of thymine may proceed with and without 

 inhibition of bacterial growth. 96 ' " It has been shown that, in general, there is no 

 strict correlation between growth inhibition by means of an unnatural base and in- 

 corporation of this base into DNA. 101 The extent of thymine replacement in the DNA 

 of bacteria depends upon both the nature of the halogen substituent 101 and the strain 

 under study. 96 ' 105 For example, in E. coli, 5-bromouracil is incorporated best. In 

 strains requiring thymine, up to 48% of the thymine 1 " 1 105 could be substituted by 

 5-bromouracil, whereas wild strains of E. coli incorporated only up to 18% of the 

 thymine. 105 Wacker et al. showed that about 70% of the thymine is substituted by 

 5-bromouracil 96 in Enierococcus stei. The study of E. coli containing 5-bromouracil in 

 their DNA showed that the DNA content in the cell remains unaltered, thereby, and 

 the cells preserve their ability to reproduce. 103 Moreover, the substitution of a por- 

 tion of thymine by 5-bromouracil is completely reversible and these mutual substitu- 

 tions are not accompanied by alterations of the hereditary properties or by typical 

 mutations preserved in the generations after the elimination of 5-bromouracil, though 

 certain modifications and alterations may take place when 5-bromouracil is incorpor- 

 ated into DNA. 103 The occasional appearance of stable mutants of a peculiar type 

 takes place, however, and that may be the result of disturbances in DNA structure. 106 

 A study of the stability (heat denaturation) and of some physical properties (spec- 

 trum, viscosity) of DNA containing 5-bromouracil did not reveal any differences 

 from the usual DNA. 105 



In a number of bacteria, e.g., E. coli, S. aureus, no incorporation into DNA of 

 growth inhibiting purine analogs, such as 8-azaguanine or other 8-azapurines, was 

 found. 107 ' 108 In B. cereus, however, it has been noticed that the bacterium incorpo- 

 rates some 8-azaguanine into its DNA. 108 - 109 



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