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Biomedical subjects

R L Willson

Publications and source records attributed to R L Willson.

At least 55 records · Page 3Linked to original sources
PubMed1978

Metronidazole (Flagyl), misonidazole (Ro 07-0582), iron, zinc and sulphur compounds in cancer therapy.

The nitro radiosensitizers, metronidazole and misonidazole, have been shown to react rapidly with the sulphydryl compounds cysteine and cysteamine in the presence of ferrous ions. Similar reactions occur in the presence of copper ions but these are much slower. The initial interactions of the drugs and of oxygen with an iron-cysteine complex are extremely rapid: in the case of oxygen reaction half-lives of 27 ms have been measured. Misonidazole also reacts rapidly with glutathione in the presence of ferrous ions and is subsequently reduced: metronidazole is reduced only slowly if at all. These reactions, which have been found to be inhibited by high concentrations of zince ions, are discussed in the light of the known radiosensitizing and chemotherapeutic efficiencies of the nitro drugs and the side effect of peripheral neuropathy sometimes observed during their clinical use.

Cysteamine↗
PubMed1978

Metronidazole (flagyl) and misonidazole (Ro-07-0582): reduction by facultative anaerobes and cytotoxic action on hypoxic bacteria and mammalian cells in vivo.

The toxic actions of the "nitro" radiosensitizers, metronidazole and misonidazole on the bacteria E. coli B/r and Serratia marcescens have been investigated under anareobic and aerobic conditions. The rates of reduction of the drugs by suspensions of these bacteria as well as by suspensions microorganisms from the rat caecum have been measured. Both drugs were reduced or were toxic only under anaerobic conditions. In all instances misonidazole was reduced more rapidly than metronidazole but metronidazole was more toxic. It is suggested that these phenomena may model those occurring with hypoxic mammalian cells in vivo and that care should be taken before automatically extrapolating in vitro data to the in vivo situation.

Anaerobiosis↗
PubMed1976

Metronidazole (Flagyl): characterization as a cytotoxic drug specific for hypoxic tumour cells.

The cytocidal properties of metronidazole against hypoxic mammalian cells are described. This chemotherapeutic action has been shown to be dependent on drug concentration and duration of exposure. The x-ray TCD50 for a murine anaplastic carcinoma was reduced from 6081 rad to 4643 rad when animals were given metronidazole orally for 36 h before radiation treatment. The effect is attributed to the direct killing of hypoxic tumour cells by a mechanism analogous to that proposed for the action of the drug on anaerobic micro-organisms. It is concluded that further work with metronidazole as a cytotoxin specific for hypoxic cells is warranted, particularly in view of the reported lack of toxicity associated with the preliminary clinical use of the drug as a radiosensitizer in man.

Animals↗
PubMed1976

Metronidazole (Flagyl): degradation by the intestinal flora.

1. Metronidazole (Flagyl) is reduced exponentially by the contents of the rat caecum in the absence of oxygen. The rate of removal is highest at pH 7 and 37 degrees. 2. Reduction of the drug is inhibited by boiling of the caecal contents, CHCl3, Cu2+, Ag+, azodicarboxylic acid bis-dimethylamide, p-chloromercuric benzoate, N-ethylmaleimide and 4,4,4-trifluoro-1,2-thienyl-1,3-butanedione. Nitrate, ethanol (3%), CO, phenol and amytal did not affect the rate of reduction. 3. It is concluded that iron-sulphur systems are involved in degradation of the drug.

Animals↗
PubMed1975

Chain reactions and radiosensitization: model enzyme studies.

The influence of persulphate ions on the radiosensitivity of dilute aqueous solutions of ribonuclease and lysozyme has been studied under a variety of conditions. Rate-constants for reactions of the sulphate radical, SO4, with a variety of solutes and transient product spectra of some of these reactions are reported. The presence of persulphate ions in general enhances the radiation sensitivity; in nitrous-oxide-saturated persulphate solution, a chain reaction has been demonstrated.

Cobalt Radioisotopes↗