BIOLOGICAL ROLE OF DEOXYPBNTOSE NUCLEIC ACIDS 441 



generally required higher concentrations and other favorable circum- 

 stances, so that the milder conditions of the biological experiments are 

 not met. However that may be, mustards in high concentrations react 

 avidly with the phosphate and amino groups of nucleic acids, producing 

 substituted ("alkylated") derivatives. Under relatively milder conditions, 

 they initiate processes leading to loss of viscosity and apparent depolymeri- 

 zation."'-^ Their ability to precipitate DNA-protein has also been noted; 

 their interaction with DNA nucleoproteins is greater than with other 

 proteins.^'' ^' Mustard derivatives having only a single reactive halogen 

 group have been shown to produce both mutations^^ and depolymerization 

 of DNA.^^ Since these cannot produce cross-linkages between proteins or 

 other substances, one alternate hypothesis relating mutagenesis to the 

 chemical potentialities of the mustards is made unlikely. It has also been 

 reported that mustard treatment causes a block in the synthesis of DNA, 

 but not in that of PXA, both in the amphibian embryo and in E. coliP •'* 



The sulfur and nitrogen mustards are in general highly toxic for living 

 cells, and they produce chromosome breakages and other effects — these 

 may or may not be extreme manifestations of the processes responsible 

 for mutagenesis (e.g., lethal mutations). It is not usually clear, however, 

 which of these types or degrees of biological effect should be considered 

 parallel with the processes being investigated in the test-tube. What does 

 seem to remain true is that DNA's are among the substances most highly 

 susceptible to the chemical action of the mutagenic mustards. 



Other mutagenic substances do not as yet furnish evidence suggesting, 

 even so loosely as this, a cause-and-effect relationship between reactivity 

 with nucleic acids and mutagenesis. Acriflavin is known to be capable of 

 precipitating wath nucleic acids and nucleotides^^ (so do many other bases) , 

 and this interaction has been proposed as an explanation for its growth- 

 inhibiting effects.^^ The actions of this and related acridines upon genetic 

 systems include mutagenic effect in bacteria," destruction of particle- 



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30 I. Berenblum and R. Schoental, Nature 159, 727 (1947). 



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32 C. M. Stevens, A. Mylroie, C. Auerbach, H. Moser, K. A. Jensen, I. Kirk, and M. 



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