EFFECTS OF ALKYLATING AGENTS ON T2 AND T4 BACTERIOPHAGES

Abstract

Inactivation of T2 and T4 bacteriophages by isotopically labelled mustard gas, 2-chloroethyl 2-hydroxyethyl sulphide, methyl methanesulphonate and ethyl methanesulphonate was studied, and the dependence on the number of alkyl groups combined with the phage DNA determined. With the difunctional agent a single-hit inactivation curve was obtained, the lethal dose being about 12 alkylations/phage DNA molecule. With monofunctional agents inactivation required a much higher extent of reaction and was a multihit process. The sites of DNA alkylated within the phage and their relative reactivities were shown to be identical with those of isolated DNA. The results suggest that inactivation by difunctional agents results from inter-strand cross-linking of DNA. With monofunctional agents it seems likely that the principal mode of inactivation results from degradation of the DNA consequent upon its alkylation.