Effects of Buthionine Sulfoximine Mediated Glutathione Depletion in Chemoresistant Human Renal Cell Carcinomas

  • G. Mickisch
  • H. Bier
  • R. Tschada
  • P. Alken
Conference paper

Abstract

Defined resistance factors play a substantial role in the characterization of chemoresistance. Glutathione metabolism is apparently involved in the expression of high chemoresistance in human renal cell carcinoma. In 35 renal cell carcinomas, primary monolayer cultures were generated, the glutathione content enzymatically determined, and depletion of glutathione instigated by buthionine sulfoximine, a specific inhibitor of glutathione biosynthesis, was studied. Furthermore, the degree of chemoresistance against doxorubicin and carboplatin was determined in an MTT microculture assay and the possibility of modulation of resistance by buthionine sulfoximine was examined.

The glutathione content amounted to 81 ±26 nM/mg protein. A high degree of chemoresistance waa associated with increased levels, a low degree with reduced levels. With appropriate culture conditions, the glutathione content could be reduced to approximately 30% of the control value. Thus, a distinct potentiation of carboplatin cytotoxicity could be detected and doxorubicin resistance was still measurably subdued.

Keywords

Oncol Doxorubicin Melphalan Cyclophosphamide Myeloma 

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Copyright information

© Springer-Verlag Berlin Heidelberg 1991

Authors and Affiliations

  • G. Mickisch
    • 1
    • 2
  • H. Bier
    • 3
  • R. Tschada
    • 1
  • P. Alken
    • 1
  1. 1.Urologische KlinikKlinikum Mannheim der Universität HeidelbergMannheim 1Germany
  2. 2.Laboratory of Molecular BiologyNational Cancer Institute, National Institutes of HealthBethesdaUSA
  3. 3.Hals-Nasen-OhrenklinikKlinikum Mannheim der Universität HeidelbergMannheim 1Germany

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