To investigate whether the difference in cellular sensitivity of Chinese hamster V79 and their H2O2-resistant variant cells (Hpr-4) to H2O2 relates to the difference in intracellular Ca2+ concentration in these cells, we measured Ca2+ concentration by calcium ion analysis after loading these cells with Fura-2/AM. Intracellular Ca2+ concentration increased in both Chinese hamster V79 and Hpr-4 cells as extracellular Ca2+ concentration increased. However, the increase in intracellular Ca2+ concentration in response to extracellular H2O2 was more pronounced in Hpr- 4 than V79 cells. H2O2 cytotoxicity of Hpr-4 but not V79 cells was also decreased in response to the increase in extracellular Ca2+ concentration. In parallel with the decrease in cytotoxicity in response to increasing extracellular Ca2+ concentration, the frequency of mitochondrial DNA single strand breaks (SSB) in Hpr-4 cells also decreased without producing observable nuclear DNA SSB. Use of permeabilized V79 and Hpr-4 cells exposed to H2O2 showed that mitochondrial DNA SSB decreased when extramitochondrial Ca2+ concentration increased. These findings indicate that elevated intracellular Ca2+ concentration may protect against H2O2-induced mitochondrial damage and cytotoxicity in these cells. (C) 2000 Elsevier Science Ireland Ltd.
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