Sulphydryls, ascorbate and oxygen as modifiers of the toxicity and metabolism of misonidazole in vitro

Equimolar concentrations of cysteamine and reduced glutathione protected against the cytotoxicity of 5 mM misonidazole (MISO), whereas 5mM ascorbate enhanced its toxicity to hypoxic CHO and HeLa cells in vitro. Protection (reappearance of a shoulder region) could also be seen when cysteamine was add...

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Bibliographic Details
Published inBritish journal of cancer Vol. 41; no. 6; pp. 892 - 900
Main Authors Taylor, Y C, Rauth, A M
Format Journal Article
LanguageEnglish
Published England Nature Publishing Group 01.06.1980
Subjects
Animals
Ascorbic Acid - pharmacology
Cell Line
Cell Survival - drug effects
Cricetinae
Cricetulus
Cysteamine - pharmacology
Female
Glutathione - pharmacology
HeLa Cells
Humans
Misonidazole - metabolism
Misonidazole - pharmacology
Nitroimidazoles - metabolism
Ovary - cytology
Oxygen
Time Factors
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Summary:Equimolar concentrations of cysteamine and reduced glutathione protected against the cytotoxicity of 5 mM misonidazole (MISO), whereas 5mM ascorbate enhanced its toxicity to hypoxic CHO and HeLa cells in vitro. Protection (reappearance of a shoulder region) could also be seen when cysteamine was added at later incubation times. These changes in toxicity were accompanied by changes in drug metabolism, as evidenced by radiochromatograms of cell extracts obtained after treatment with 14C-labelled MISO. In contrast, radiochromatograms obtained from cells treated with toxic levels of MISO (75 mM) under aerobic conditions indicated no drug metabolism. Both toxicity and drug metabolism could be immediately halted by introducing O2 during hypoxic exposure to MISO. These observations are discussed in terms of a possible model for the metabolism-mediated toxicity of MISO and the roles which sulphydryls and O2 may play.
ISSN:0007-0920
1532-1827
DOI:10.1038/bjc.1980.166