The mechanism of Cr(VI) genotoxicity has still not been elucidated. We used Fpg-modified comet assay to assess direct-oxidative DNA damage on human lung (A549) and bronchial (BEAS-2B) cells exposed to 0.1, 0.5, 1.0 and 10 mu M sodium chromate for 0.5, 1 and 4 h. Moreover we evaluated apoptosis by morphological analysis and caspase-3 activity, also after 24 h. On A549 cells a time-dependent DNA damage, expressed as tail DNA%, beginning from 0.5 mu M was found. For oxidative DNA damage an induction after 30 min to 0.5 mu M decreasing with time, and a time-dependent increase at 10 mu M was found, indicating for low Cr(VI) concentration the oxidative stress as the first event followed by direct DNA damage and for the highest concentration a time-dependent increase in oxidative DNA damage. On BEAS-2B cells DNA damage was induced within 1 h at 0.5-10 mu M, without changes with time, showing that BEAS-2B cells are able to resist to Cr(VI) genotoxicity. Early oxidative DNA damage at 0.1 mu M decreasing with time was also found. Significant apoptosis was observed by morphological analysis in A549 cells and to a lower extent in BEAS-2B at 10 mu M. The exposure to 10 mu M induced caspase-3 activity after 4 h in BEAS-2B and after 24 h in A549 cells. The findings show a higher responsiveness of A549 cells to genotoxic effect of Cr(VI) and early transient oxidative DNA damage in BEAS-2B. The results emphasize the suitability of this experimental model to evaluate the early genotoxic response of different cells to non-cytotoxic concentrations of Cr(VI) on target organ.
|Titolo:||Direct-oxidative DNA damage and apoptosis induction in different human respiratory cells exposed to low concentrations of sodium chromate|
|Data di pubblicazione:||2010|
|Appare nelle tipologie:||1.1 Articolo in rivista|