Mutagenic Alkylating Agents 317 



formed within one molecule which then becomes distorted. 

 When the nucleoprotamine is treated, crosslinks are formed 

 between different DNA molecules which are thereby rendered 

 insoluble and form a gel when the nucleoprotein is dispersed 

 in strong salt. The greater effectiveness of the bifunctional 

 reagents is attributed to crosslinking which is a much more 

 efficient process of spoiling DNA than the isolated blocking 

 of phosphate groups which is the only reaction produced by 

 the monofunctional reagents. 



The triesters formed when the phosphate groups of DNA 

 are alkylated, are unstable and occasionally hydrolyse to give 

 a break in one of the polynucleotide strands of DNA. These 

 breaks are masked by the other chain of the twin molecule 

 and can only be revealed by special techniques. The formation 

 of these hidden breaks may provide a mechanism for the 

 rearrangement within a DNA molecule without at the same 

 time so altering its configuration as to make it useless to the 

 cell. In this way DNA might be made to transmit an altered 

 code. 



Acknowledgement 



This investigation has been supported by grants to the Royal Cancer 

 Hospital and Chester Beatty Research Institute from the British 

 Empire Cancer Campaign, the Jane Coffin Childs Memorial Fund for 

 Medical Research, the Anna Fuller Fund, and the National Cancer 

 Institute of the National Institutes of Health, U.S. Public Health 

 Service. 



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