Arsenic-Induced Carcinogenesis and Immune Dysregulation

Abstract

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.

Importance of monitoring arsenic methylation metabolism in acute promyelocytic leukemia patients receiving the treatment of arsenic trioxide

“…The ATRA and ATO combination therapy for APL has brought significant advantages in both laboratory studies and clinical settings [ 1 ], especially when compared to the ATRA and anthracycline-based chemotherapy [ 3 , 7 , 8 ], suggesting that the addition of arsenic in the front-line therapy would guarantee a longer remission duration and survival. However, ATO was still considered as a potential toxicant as well as a carcinogen, which was commonly observed after long-time exposure to environmental contamination [ 18 , 19 ]. In our previous study, the incidence of mild liver dysfunction (15.2%) and hepatic steatosis (42.9%) in patients was significantly higher compared to the healthy controls [ 5 ].…”

Reproductive Toxicity of Arsenic: What We Know and What We Need to Know?

“…Recent studies revealed that chronic arsenic exposure induces oxidative DNA damage, reduced thymic functions and subsequent immunosuppression in childhood [76]. Arsenic is well known inducer of chromosomal aberration which involves both clastogenic and a euploidogenic [77]. Recent studies documented cytogenetic monitoring by using chromosomal aberration and micronuclei assay in order to observe genotoxic effects of arsenic in human and animal population [78].…”

Heavy Metals in Acrylic Color Paints Intended for the School Children Use: A Potential Threat to the Children of Early Age

“…Exposure to As plays an important role in the development of vascular endothelial deformity in the human body, leading to a diminution in the bioavailability and generation of nitric oxide. Besides, prolonged As exposure causes high oxidative stress, which leads to cardiovascular and central nervous system dysfunction [21] and skin cancer [22]. Cd exposure produces skin tumors and toxicity to the kidneys [23], Cd is readily retained in the proximal tubular cells of the human body.…”