Enhancement of misonidazole cytotoxicity by iron

A. Samuni*, E. A. Bump, J. B. Mitchell, J. M. Brown

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

The toxicity of misonidazole (MISO) to hypoxic Chinese hamster ovary (CHO) cells in serum-free medium is enhanced by Fe(III)-EDTA. Enhancement of MISO cytotoxicity by a factor of 1·6 was seen with 2μm Fe(III)-EDTA, while 200 μm Fe(III)-EDTA results in sensitization by a factor of 2·0. Treatment of CHO cells with the iron chelator desferal resulted in protection against the hypoxic cytotoxicity in MISO (approximate protection factor of 2·5 with 100 μm desferal). Similar results were obtained with Chinese hamster V79 cells. Fe(III)-EDTA also enhanced binding of [2-14C] MISO to cellular macromolecules while desferal decreased binding of MISO to cellular macromolecules. These results suggest that iron plays an important role in the reductive metabolism of MISO and that modification of the intracellular metal ion status may be a useful approach to modulating the biological effect of nitro compounds.

Original languageEnglish
Pages (from-to)77-83
Number of pages7
JournalInternational Journal of Radiation Biology
Volume49
Issue number1
DOIs
StatePublished - 1985

Keywords

  • Iron
  • Misonidazole
  • Nitro reduction

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