Fig. 6. Inhibition of glutathione synthesis sensitises PMDOs to short-term oxaliplatin treatment.

a PMDOs were treated for 24 h with BSO (100 μM) or solvent. Reduced glutathione (GSH) levels were then measured as described in the 'Materials and methods'. The barplot shows reduced GSH levels in control- and BSO-treated PMDOs. b, c Two distinct PMDOs were treated for 1 h with oxaliplatin at the indicated concentrations in the presence or absence of BSO (100 μM). The surviving cell fractions were then quantified by Cell Titer Glo. All values are plotted as % of untreated controls. d Bar graphs showing a quantification of Pt adducts in the genomic DNA of PMDOs following treatment with oxaliplatin (200 μM) with or without BSO (100 μM) and in the presence or absence of reduced GSH. e Western blot analysis of pRPA, GCLC and actin protein expression levels in PMDOs following a 5 or 24 h exposure to oxaliplatin (200 μM) in the presence or absence of BSO. f Experimental setup of the long-term regeneration experiments. g, h Two distinct PDOs were treated with oxaliplatin (200 μM) and BSO (100 μM) alone and in combination for 1 h at 42 °C. Three weeks after drug washout the regenerative capacity was assessed in all conditions by Cell Titer Glo measurements and photographs.