. Ciba Foundation symposium on drug resistance in micro-organisms: mechanisms of development. Drug resistance in microorganisms. 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
. Ciba Foundation symposium on drug resistance in micro-organisms: mechanisms of development. Drug resistance in microorganisms. 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 (, acid consumed to maintain pH at 7) when 0 • 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 Please note that these images are extracted from scanned page images that may have been digitally enhanced for readability - coloration and appearance of these illustrations may not perfectly resemble the original Ciba Foundation; Wolstenholme, G. E. W. (Gordon Ethelbert Ward); O'Connor, Cecilia M. (Cecilia Mary), 1927-. Boston, Little, Brown
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