Effect of BSO and etanidazole on neurofilament degradation in neonatal rat spinal cord cultures

S. T. Palayoor*, E. A. Bump, D. M. Saroff, J. R. Delfs, C. Geula, L. Menton-Brennan, S. J. Hurwitz, C. N. Coleman, M. A. Stevenson

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

Peripheral neuropathy is the major dose-limiting toxicity of the hypoxic cell sensitiser, etanidazole. Previous work from this laboratory using cultured neuronal cell lines suggested that nitroimidazole-induced degradation of neurofilament proteins might be the critical biological event mediating this neurotoxicity. The purpose of the present study was to develop the neurofilament degradation assay in an organotypic spinal cord culture system with the goal of developing strategies for optimising sensitiser efficacy as well as ameliorating nitroimidazole-induced neurotoxicity. Spinal cord cultures were treated with etanidazole and neurofilament protein degradation was analysed by immunoblot analysis. Spinal cord cultures exposed to etanidazole exhibited a dose-dependent loss of parent neurofilament proteins, with concomitant appearance of low molecular weight degradation products. The potential neurotoxic effect of L, S-buthionine sulphoximine (BSO), a compound that enhances the radiosensitising effectiveness of 2-nitroimidazoles, was also screened in this assay system. BSO alone, at concentrations up to 100 μM, did not promote neurofilament degradation. BSO (20 μM) enhanced the effect of etanidazole on neurofilament degradation by a dose-modifying factor of 1.6 ± 0.5. Since 20 μM BSO is expected to enhance etanidazole radiosensitisation of hypoxic cells by a larger factor, this suggests that a therapeutic gain could be achieved using BSO in combination with etanidazole in radiation therapy.

Original languageEnglish (US)
Pages (from-to)S117-S121
JournalBritish Journal of Cancer
Volume74
Issue numberSUPPL. XXVII
StatePublished - Jan 1 1996

Keywords

  • Hypoxia
  • Neurotoxicity
  • Radiosensitisers
  • Sulphydryl depletion

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Palayoor, S. T., Bump, E. A., Saroff, D. M., Delfs, J. R., Geula, C., Menton-Brennan, L., Hurwitz, S. J., Coleman, C. N., & Stevenson, M. A. (1996). Effect of BSO and etanidazole on neurofilament degradation in neonatal rat spinal cord cultures. British Journal of Cancer, 74(SUPPL. XXVII), S117-S121.