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MoDCs populations generated from three healthy volunteers displayed the phenotype responsive to NiSO4 and non-responsive to sodium dodecyl sulfate (SDS). Clear up-regulation of IL-1beta mRNA as well as CD54, CD86 and HLA-DR expression in response to NiSO4 (250 microM) was detected after 48 hrs of exposure. No up-regulation of evaluated surface antigens was observed following the treatment with SDS (150 microM). TCPP (150 microM) similarly to NiSO4 induced up-regulation of IL-1beta mRNA, CD54, CD86, but not HLA-DR expression. The response to TCPP showed less inter-individual variability, however it was weaker in comparison to the response to NiSO4. The results suggest that platinum salts can induce in MoDCs phenotypical changes characteristic for skin sensitizers.

The purpose of the study was to characterize the involvement of reactive oxygen species (ROS) in mediating the cytotoxic effects of arsenic trioxide (ATO) in combination with sulindac or its metabolites: sulfide (SS) and sulfone (SF) on human leukemic cell lines. Jurkat, HL-60, K562, and HPB-ALL cells were exposed to the drugs alone or in combinations. Cell viability was measured using WST-1 or XTT reduction tests and ROS production by dichlorodihydrofluorescein diacetate staining (flow cytometry). Modulation of (a) intracellular glutathione (GSH) level was done by using L: -buthionine sulfoximine (BSO) or diethylmaleate (DEM), (b) NADPH oxidase by using diphenyleneiodonium (DPI), and (c) MAP kinases by using SB202190 (p38), SP600125 (JNK), and U0126 (ERK) inhibitors. ATO cytotoxicity (0.5 or 1 μM) was enhanced by sulindacs, with higher activity showed by the metabolites. Strong cytotoxic effects appeared at SS and SF concentrations starting from 50 μM. The induction of ROS production seemed not to be the major mechanism responsible for the cytotoxicity of the combinations. A strong potentiating effect of BSO on ATO cytotoxicity was demonstrated; DEM (10-300 μM) and DPI (0.0025-0.1 μM; 72 h) did not influence the effects of ATO. Some significant decreases in the viability of the cells exposed to ATO in the presence of MAPK inhibitors comparing with the cells exposed to ATO alone were observed; however, the effects likely resulted from a simple additive cytotoxicity of the drugs. The combinations of ATO with sulindacs offer potential therapeutic usefulness.

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