Effect of Radiosensitizing Agents on DNA Strand Breaks and Their Rapid Repair during Irradiation

The number of strand breaks in the DNA of bacteriophage T4 and of three strains of Escherichia coli was measured after exposure to γ-radiation in the presence and absence of radiosensitizing agents. Little effect of these agents on break production was observed with intact bacteriophage. Both sensitization and protection were observed with different agents when the phage was lysed to expose the DNA before irradiation. Both effects were attributed to interactions with the OH radicals produced in the irradiated solution. However, these effects did not appear to play an important role in the production of DNA strand breaks during the irradiation of intact E. coli cells. In this case, the presence of iodate, iodoacetamide, or N-ethyl maleimide during irradiation inhibited the DNA polymerase I-dependent repair of single-strand breaks in the DNA. No effect of these compounds was observed with E. coli pol A cells which lack this rapid repair system. Mild detergents also inhibit the rapid repair of strand breaks. It is concluded that the radiosensitizing agents affect DNA repair in intact E. coli cells and that the main target of their action under the conditions used is probably the cell membrane.