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Biomedical subjects

R C Knight

Publications and source records attributed to R C Knight.

31 records · Page 2Linked to original sources
PubMed1981

Interaction of nitroimidazole drugs with DNA in vitro: structure-activity relationships.

An electrolytic reduction system has been developed to model the cytotoxic action of a range of nitroimidazole drugs against DNA hypoxic cells or anaerobic microorganisms. THe degree of damage induced by these drugs (measured as the release of [14C]-dT from DNA) and their relative rates of reduction have been correlated with their redox potentials. The results show that the correlation of drug-induced damage and electron affinity is related to the amount of drug reduced, and supports the hypothesis that at the molecular level the cytotoxic mechanism of reduced nitroimidazoles is identical in hypoxic mammalian cells, bacteria and protozoa.

Cell Survival↗
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↗
PubMed1978

Measuring IgG anti-A/B titres using dithiothreitol (DTT).

In comparing the use of the sulphydryl compounds 2-mercaptoethanol (2ME) and dithiothreitol (DTT) a rapid one-stage technique for titrating IgG anti-A and anti-B using DTT in an antiglobulin test was tried. The results correlated well with those obtained by either of the two-stage methods using 2ME or DTT.

ABO Blood-Group System↗
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↗