Mechanisms and Immune Dysregulation in Arsenic Skin Carcinogenesis

Long-term exposure to arsenic is associated with cancers of lung, urinary bladder, kidney, liver and skin. Arsenic carcinogenesis might result from oxidative stress, altered growth factors, chromosomal abnormality, immune dysregulation, and aberrant epigenetic regulations. Bowen’s disease (As-BD) is the most common form of arsenic-induces skin cancers and is characterized by chronicity, multiplicity, and predisposition in sun-spare skin. However, only about 1% of the population exposed to arsenic developped skin cancers, indicating the host immune response plays an important modulatory role in skin carcinogenesis. In this review, we review the pathomechanisms of arsenic skin carcinogenesis and the immune interactions. Arsenic affects innate and adaptive immune responses through CD4+ T cells, monocytes, macrophages, and Langerhans cells. In skin of As-BD, CD4+ T cells undergo selective and differential apoptosis via Fas-FasL interaction. Numbers and dendrites of Langerhans cells are reduced in As-BD lesions. There is a defective homeostasis and aberrant trafficking of Langerhans cells. Such information is essential to understand the molecular mechanism for arsenic carcinogenesis in both skin and in internal organs.