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Biomedical subjects

D I Edwards

Publications and source records attributed to D I Edwards.

65 records · Page 4Linked to original sources
PubMed1979

Mechanism of action of nitroimidazole antimicrobial and antitumour radiosensitizing drugs. Effects of reduced misonidazole on DNA.

Electrolytic reduction of the hypoxic tumour cell radiosensitizing drug misonidazole was carried out at a controlled potential under anaerobic conditions in the presence of Escherichia coli DNA. During the reduction process the DNA was examined by viscometry, thermal hyperchromicity, melting and renaturation profiles, hydroxyapatite chromatography, agarose gel electrophoresis and alkaline sucrose density gradient centrifugation. The reduced drug decreases the viscosity, hyperchromicity and renaturation of DNA. These effects are consistent with strand breakage of the molecule which was corroborated by finding an increase in the single-strand content of DNA, increased migration and loss of fluorescence intensity on agarose gels and sedimentation to a less dense region in alkaline sucrose density gradients. The results are discussed in relation to postulated mechanisms of the selective toxicity of the drug towards anaerobes and cytotoxicity of electron affinic radiosensitizers of hypoxic tumour cells.

Antibiotics, Antineoplastic↗
PubMedDate not supplied

Structure-cytotoxicity relationships of nitroimidazoles in an in vitro system.

Correlations of cytotoxicity of nitroimidazoles and their electron affinity depend upon the degree of reduction of the drugs. If the end-point chosen to assess cytotoxicity is one at which incomplete reduction has occurred the slope of the correlation is positive, with respect to E71, but if measurements are taken after complete reduction of the drugs the slope is a negative one. The production of nitrite ion by 5-nitroimidazoles depends on the base composition of DNA suggesting that the active agent responsible for cytotoxicity is the one-electron radical anion, R--NO2-.

Cell Survival↗