Concentration-dependent cellular responses of arsenic in keratinocytes

Arsenic (As) is considered as a human carcinogen or tumor-promoting agent. Epidemiological evidences indicated that cancer incidences of residents in arseniasis areas were significantly higher in multiple organs, including urinary bladder, lungs, and especially the skin, than those living in non-arseniasis areas. In the context of skin cancers, keratinocytes are believed to be the main target cells in As carcinogenesis. Therefore, we discuss the significance of keratinocyte-specific effects of As on skin carcinogenesis. As is known to be cytotoxic because of its chemical reactions with the thiol group of proteins and its ability to generate free radicals during cellular metabolism. However, at relatively low concentrations, As shows stimulatory effects, such as cell activation and proliferation. Because long-term As exposure is associated with skin carcinogenesis, we reviewed the mechanisms of As-induced keratinocyte dysfunctions by means of time- and concentration-dependent cellular responses. The mechanisms and interactions underlying As-induced keratinocyte dysfunctions not only provide a model of As in skin carcinogenesis process but also help in understanding the regulation of As carcinogenesis in other internal organs.