Hexavalent chromium [Cr(VI)] is one of the most common environmental carcinogen causing lung cancer in humans; however, the mechanism of Cr(VI) carcinogenesis remains elusive.
This study aimed to (i) identify biological pathways that are consistently modulated by Cr(VI) in the lung through the compilation of transcriptomic-based databases, (ii) predict interactions between epigenetic regulators and transcriptional responses, and (iii) relate findings to previous literature to postulate a mechanism of action underlying Cr(VI)-induced lung cancer involving changes in genomic/epigenomic signatures.
Hexavalent chromium [Cr(VI)] is known to cause lung cancer in workers of certain industries, but an association with stomach cancer is uncertain and widely debated.
Hexavalent chromium [Cr(VI)] is a common human carcinogen associated with lung cancer and other pulmonary diseases as exposure to excessive Cr(VI) induces malignant transformation in human lung epithelial cells.
We conducted a MOA analysis for Cr(VI)-induced lung cancer evaluating toxicokinetic and toxicological data in humans and rodents and mechanistic data to assess plausibility, dose-response, and temporal concordance for potential MOAs.
Since humans are frequently exposed to both Cr(VI) and PAHs, it is possible that Cr(VI) and PAHs have a synergistic effect on mutagenecity and cytotoxicity that contributes to the high incidence of lung cancer associated with exposure to both agents.