304 P. Alexander, S. F. Cousens and K. A. Stagey 



These observations seemed to be very difficult to reconcile 

 with the view that the radiomimetic alkylating agents exerted 

 their effect by combining with DNA, and led us to examine 

 the reaction of a series of water-soluble aromatic nitrogen 

 mustards with proteins and DNA. The relative rates of reac- 

 tion were expressed as a competition factor (Ogston, 1948) 

 which was defined as: 



Amount of mustard combined with 



macromolecule 



Amount of mustard hydrolysed by 



water 



X 



concentration of 

 macromolecule 



The concentration of macromolecule was expressed as a 

 molarity based on the total number of groups present which 

 can be alkylated. Table III shows that there is no correlation 



Table III 



between reactivity with DNA and biological activity. All 

 mustards carrying a positive charge reacted readily while 

 those like chlorambucil which have a negative charge (i.e. the 

 ionized carboxyl group) at pH 7 fail to react. Experiments 



