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Direct‐oxidative DNA damage and apoptosis induction in different human respiratory cells exposed to low concentrations of sodium chromate
Author(s) -
Cavallo Delia,
Ursini Cinzia Lucia,
Fresegna Anna Maria,
Ciervo Aureliano,
Maiello Raffaele,
Rondi Bruna,
D'Agata Velia,
Iavicoli Sergio
Publication year - 2010
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.1487
Subject(s) - genotoxicity , dna damage , comet assay , a549 cell , oxidative stress , microbiology and biotechnology , apoptosis , chemistry , dna , toxicity , biology , biochemistry , organic chemistry
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 μ 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 μ m was found. For oxidative DNA damage an induction after 30 min to 0.5 μ m decreasing with time, and a time‐dependent increase at 10 μ 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 μ 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 μ 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 μ m . The exposure to 10 μ 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. Copyright © 2009 John Wiley & Sons, Ltd.