Mutagenic Alkylating Agents 



303 



Since the epoxides react much more slowly than the mustards 

 and also since the proportion which hydrolyses is much greater, 

 it is not possible to determine the extent of combination with 

 amino groups. Using excess epoxide the absorption spectrum 

 of the DNA is slightly altered after 50 per cent of the 

 phosphate groups have become esterified, and this indicates 

 that some reaction with the purine" or pyrimidine bases has 

 occurred. No change in the spectrum was observed immedi- 

 ately after comparable treatment with aliphatic nitrogen 



60 - 



160 240 



TIME (mIN.) 



Fig. 3. Rate of alkali produced (i.e., acid consumed 



to maintain pH at 7) when • 1 % DNA was treated 



with a 2% solution of propylene oxide at 37° C. 



mustards and this is another illustration of the greater 

 reactivity of epoxides wdth amino groups (cf. Table I). 



On extending our investigations to other aromatic mustards 

 we found that some did not combine significantly with DNA 

 in solution. A notable example was chlorambucil, 



C00H(CH2). 



-N 



CH2CH2CI 

 CI12* CH2* CI 



a compound used clinically and found by Fahmy and Fahmy 

 (1956) to have the highest mutagenic activity of any mustard. 



