The effect of glutathione depletion by diamide, diethyl maleate or buthione sulfoximine on the surface structure of mouse L-cells.
Radiosensitizers that act by reducing glutathione levels have been studied by many workers as agents to enhance the killing of hypoxic tumour cells. In this paper we describe a scanning electron microscope (SEM) study of the surface morphology of mouse L-cells after exposure to three of these: diazenedicarboxylic acid bis N,N-dimethylamide (diamide), DL-buthionine-S,R-sulfoximine (BSO) and diethyl maleate (DEM). Diamide at 0.1 to 0.6 mMol/L for 10 min produced large blebs on the cell surface as seen in the SEM. Transmission electron microscope (TEM) images show that these are clear, featureless regions of cytoplasm. BSO treatment for 24 h at 0.5 to 2.0 mMol/L, by contrast, left the surface similar to control cells. DEM at 0.5 mMol/L for 2 h produces small blebs over the cell surface and a reduction in the number of microvilli. A combined 24 h BSO treatment with 2 h of DEM produced large blebs, which were similar in TEM micrographs to those produced by diamide. Thus, although all three sensitizers reduce glutathione levels, they have different effects on cellular morphology and hence such secondary effects may account for the different degrees of radiation sensitization seen with these agents.
D000818:Animals; D001391:Azo Compounds / Q000494:pharmacology*; D019328:Buthionine Sulfoximine; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure*; D003958:Diamide / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism*; D007739:L Cells / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D008298:Maleates / Q000494:pharmacology*; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051379:Mice; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning
D001391:Azo Compounds; D008298:Maleates; D003958:Diamide; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; C014476:diethyl maleate; D005978:Glutathione