Short-term and long-term exposure to hexavalent chromium alters 53BP1 via H3K18ac and H3K27ac

Add time:08/17/2019    Source:sciencedirect.com

Hexavalent chromium (Cr(VI)) is a well-known human carcinogen and a strong oxidizer that causes severe DNA damage. However, the associations between epigenetic dysregulation and DNA damage have not been well-characterized. In this study, we evaluated the effects of short-term and long-term exposure to Cr(VI) in human bronchial epithelial (16HBE) cells. Then, we explored the role of epigenetic modification in Cr(VI)-induced DNA damage. We found that short- and long-term exposure to Cr(VI) induced DNA damage and reduced the expression 53BP1, but increased the expression of other DNA repair mediators. Short- and long-term exposure to Cr(VI) reduced the levels of H3K18ac and H3K27ac and reduced their enrichment at the promoter of 53BP1. Long-term Cr(VI) exposure resulted in multiple malignant characteristics including cell invasion, migration, and tumorgenicity. These data demonstrated that reduced H3K18ac and H3K27ac following Cr(VI) treatment contributed to the suppression of 53BP1. Our study demonstrated that epigenetic changes and DNA damage responses are involved in short-term toxicity and long-term carcinogenesis induced by Cr(VI).

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