2
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Apoptosis or necrosis: intracellular levels of glutathione influence mode of cell death.

      Biochemical Pharmacology
      Alkylating Agents, pharmacology, Apoptosis, drug effects, Camptothecin, Cell Death, Cell Line, metabolism, pathology, Chlorambucil, DNA, isolation & purification, Dactinomycin, Glutathione, analysis, Humans, Melphalan, Necrosis

      Read this article at

      ScienceOpenPubMed
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          The effect of lowering intracellular glutathione (GSH) concentrations on the toxicity of alkylating agents, and RNA synthesis inhibitor and topoisomerase 1 and 2 inhibitors to a number of human leukaemic cell lines were evaluated. By using the GSH synthesis inhibitor DL-buthionine-(S,R)-sulfoximine (BSO), GSH levels were artificially reduced. Cells with low GSH concentrations were exposed to a number of cytotoxic agents and the resultant mode of cell death was analysed using morphological and biochemical criteria. It was found that untreated cells exposed to the above drugs underwent apoptosis to varying extents. However, the toxicity of alkylating agents was dramatically increased to all cell lines on lowering GSH levels, with the mode of cell death switching from apoptosis to necrosis. The reduction of GSH levels had no effect on the toxicity of actinomycin-D, camptothecin or etoposide, nor did it affect the mode of cell death induced by these agents. These observations suggest that modulation of GSH levels effect the toxicity of alkylating agents and that GSH influences the mode of cell death induced by alkylating agents.

          Related collections

          Author and article information

          Comments

          Comment on this article