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/sup -3/) and its metabolites (1 mmole dm/sup -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/sup -3/ misonidazole alone, whereas the initial enhancement ratio indicates that the metabolites potentiate the action of misonidaxole. 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.
- Research Organization:
- Mount Vernon Hospital, Northwood, England
- OSTI ID:
- 5742052
- Journal Information:
- Radiat. Res.; (United States), Vol. 93:3
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
59 BASIC BIOLOGICAL SCIENCES
ESCHERICHIA COLI
RADIOSENSITIVITY
METABOLITES
RADIOSENSITIVITY EFFECTS
MISONIDAZOLE
ANOXIA
COBALT 60
GAMMA RADIATION
IMIDAZOLES
NITRO COMPOUNDS
NITRO-GROUP DEHYDROGENASES
TAN
AMINES
ANTINEOPLASTIC DRUGS
AZINES
AZOLES
BACTERIA
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
COBALT ISOTOPES
DRUGS
ELECTROMAGNETIC RADIATION
ENZYMES
HETEROCYCLIC COMPOUNDS
INTERMEDIATE MASS NUCLEI
INTERNAL CONVERSION RADIOISOTOPES
IONIZING RADIATIONS
ISOMERIC TRANSITION ISOTOPES
ISOTOPES
KETONES
MICROORGANISMS
MINUTES LIVING RADIOISOTOPES
NUCLEI
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
OXIDOREDUCTASES
PIPERIDINES
PYRIDINES
RADIATIONS
RADIOISOTOPES
RADIOSENSITIZERS
YEARS LIVING RADIOISOTOPES
560131* - Radiation Effects on Microorganisms- Basic Studies- (-1987)
550700 - Microbiology