Relationship between thiol depletion and chemosensitization in a transplantable murine bladder tumor

P. Tomashefsky, M. Astor, Ralph W deVere White

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

The effect of pretreating the C3H/He mouse MBT-2 tumor with diethyl maleate (DEM), buthionine-S R-sulfoximine (BSO), or misonidazole (MISO) before administration of cyclophosphamide (CTX) was studied with the use of tumor volume-doubling time delay as an endpoint. The kinetics of glutathione (GSH) depletion and regeneration in the tumor and in the host liver were determined after treatment with the thiol-depleting agents. CTX was administered at appropriate time points. MISO was the most effective chemosensitizer at a time point at which tumor GSH content was 80-85% of the control value. Both BSO and DEM were chemosensitizers in relation to the degree they had reduced tumor GSH levels. This chemosensitization was significant at 50% GSH reduction. By combining MISO and BSO at doses lower than previously used for each agent alone, highly effective sensitization of subsequent CTX was obtained.

Original languageEnglish (US)
Pages (from-to)1233-1238
Number of pages6
JournalJournal of the National Cancer Institute
Volume74
Issue number6
StatePublished - 1985
Externally publishedYes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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