Hexavalent chromium(Cr(Ⅵ))is a potent human lung carcinogen,and numerous epidemiological studies have been performed to determine its carcinogenicity.While Cr(Ⅵ)-induced DNA damage has been well-documented,few studies has been focused on Cr(Ⅵ)-associated epigenetic alterations and their role in carcinogenesis.In this study,we showed that Cr(Ⅵ)treatment caused DNA damage and activated the pathway for the repair of DNA double-strand breaks(DSBs)in human bronchial epithelial cells(16HBE).In contrast,we found that among examined proteins,only 53BP1 in the DSB repair pathway was significantly and specifically reduced in response to Cr(Ⅵ)rather than other tested well-known toxicants.Mechanistically,we found a number of histone modifications,including histone marks for 53BP1 recruitment(H4K20me and H3K79me2)and for transcriptional activation(H3K18ac and H3K27ac),were significantly decreased at global level in Cr(Ⅵ)-treated cells.Specifically,both H3kl8ac and H3K27ac were found to be significantly reduced at the promoter of 53BP1,suggesting a potential mechanism for the downregulated 53BP1 in Cr(Ⅵ)-treated cells.Collectively,our results suggested a mechanistic link between epigenetic alterations,impaired DSB repair pathway by reducing the level of 53BP1 and its recruitment,and Cr(Ⅵ)-associated carcinogenesis.