Metabolic potentiation of the radiosensitization of hypoxic bacterial cells afforded by nitroaromatic compounds.
Prolonged preirradiation incubation of nitroaromatic radiosensitizers with Escherichia coli cells has been found to increase the degree of radiosensitization of the cells in anoxia. Studies with E. coli strains which differ in their nitroreductase activity indicate that the increase in sensitization arises from the action of metabolites produced by the nitroreductase system of the cell. The metabolites alone appear to decrease the extrapolation number of irradiated hypoxic cells and when combined with the parent compound give a biphasic survival curve. The combination of misonidazole (1 mmole dm-3) and its metabolites (1 mmole dm-3) gave initial and final enhancement ratios of 2.4 and 1.4, respectively. The final enhancement ratio is that expected for 1 mmole dm-3 misonidazole alone, whereas the initial enhancement ratio indicates that the metabolites potentiate the action of misonidazole. The preirradiation incubation effect is removed by dithiothreitol at concentrations which do not affect the radiosensitization level of the nitroaromatic sensitizer. This result indicates that the active metabolite probably depletes a certain amount of the free-thiol compounds inside the cell which assist in the repair of radiation-induced damage.
D000098:Acetophenones / Q000378:metabolism / Q000494:pharmacology; D004307:Dose-Response Relationship, Radiation; D004926:Escherichia coli / Q000378:metabolism* / Q000528:radiation effects; D008920:Misonidazole / Q000378:metabolism / Q000494:pharmacology; D009593:Nitroimidazoles / Q000378:metabolism / Q000494:pharmacology; D010100:Oxygen; D011838:Radiation-Sensitizing Agents / Q000378:metabolism / Q000494:pharmacology*; D013997:Time Factors; D014216:Triacetoneamine-N-Oxyl / Q000378:metabolism / Q000494:pharmacology
D000098:Acetophenones; D009593:Nitroimidazoles; D011838:Radiation-Sensitizing Agents; C001972:4-nitroacetophenone; D014216:Triacetoneamine-N-Oxyl; C038256:1-(2-phenoxyethyl)-2-nitroimidazole; D008920:Misonidazole; D010100:Oxygen