Enhancement of the lethal effect of 2,2′-dichlorodiethylamine on Escherichia coli by thiol-binding agents

• Published in: Biochimica et biophysica acta Vol. 208; no. 2; pp. 310 - 316
• Main Authors: Titani, Yoiti, Katsube, Yutaka
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 12.05.1970
• Subjects: Alkylating Agents - pharmacology; Anti-Bacterial Agents - pharmacology; DNA, Bacterial; Drug Synergism; Escherichia coli - drug effects; Ethylmaleimide - pharmacology; Radiation-Sensitizing Agents - pharmacology
• DOI: 10.1016/0304-4165(70)90250-3
• ISSN: 0304-4165; 0006-3002

Using a bifunctional alkylating agent 2,2′-dichlorodiethylamine as a radiomimetic substance, the effect of some thiol-binding agents on the lethal effects of the radiomimetic substance on Escherichia coli B/r and B s−1 was investigated. N-Ethyl-malameide and showdomycin, an antibhiotic containing a maleimide moeity, effectively sensitized both of these Escherichia coli strains to the lethal effect of the radiomimetic; but p-chloromercuriphenylsulfonate, a powerful radiosensitizer, had no effect no either strains. Surviving fractions of the cell plotted against the concentration of radiomimetic gave straight lines with slopes corresponding to the different concentrations of the sensitizer. Although showdomycin was always more effective than N-ethylmaleimide, the dose-modifying factors on B/r and B s−1 were similar for the showdomycin and N-ethylmaleimide. This radiomimetic sensitization seems to be specific not only for the thiol-binding ability but also for some structural property of the thiol-binding agent. These facts suggest that, in spite of a similarity in the action of radiation and radiomimetics on the DNA of living cells, the actual target may not be the same for both reactants.