Arsenic-induced carcinogenesis and immune dysregulation

Arsenic, a metal ubiquitously distributed in the environment, remains an important global health threat. Drinking arsenic-contaminated water is the major route of human exposure. Exposure to arsenic contributes to several malignancies, in the integumentary, respiratory, hepatobiliary, and urinary systems. Cutaneous lesions are important manifestations after long-term arsenic exposure. Arsenical skin cancers usually herald the development of other internal cancers, making the arsenic-induced skin carcinogenesis a good model to investigate the progression of chemical carcinogenesis. In fact, only a portion of arsenic-exposed humans eventually develop malignancies, likely attributed to the arsenic-impaired immunity in susceptible individuals. Currently, the exact pathophysiology of arsenic-induced carcinogenesis remains elusive, although increased reactive oxidative species, aberrant immune regulations, and chromosome abnormalities with uncontrolled cell growth might be involved. This review discusses how arsenic induces carcinogenesis, and how the dysregulated innate and adaptive immunities in systemic circulation and in the target organs contribute to arsenic carcinogenesis. These findings offer evidence for illustrating the mechanism of arsenic-related immune dysregulation in the progression of carcinogenesis, and this may help explain the nature of multiple and recurrent clinical lesions in arsenic-induced skin cancers.