Arsenic Carcinogenesis in the Skin

Authors: HsinSu Yu WeiTing Liao CheeYin Chai

Publish Date: 2006/06/29

Volume: 13, Issue: 5, Pages: 657-666

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Abstract

Chronic arsenic poisoning is a world public health issue Longterm exposure to inorganic arsenic As from drinking water has been documented to induce cancers in lung urinary bladder kidney liver and skin in a dose–response relationship Oxidative stress chromosomal abnormality and altered growth factors are possible modes of action in arsenic carcinogenesis Arsenic tends to accumulate in the skin Skin hyperpigmentation and hyperkeratosis have long been known to be the hallmark signs of chronic As exposure There are significant associations between these dermatological lesions and risk of skin cancer The most common arsenicinduced skin cancers are Bowen’s disease carcinoma in situ basal cell carcinoma BCC and squamous cell carcinoma SCC Arsenicinduced Bowen’s disease AsBD is able to transform into invasive BCC and SCC Individuals with AsBD are considered for more aggressive cancer screening in the lung and urinary bladder AsBD provides an excellent model for studying the early stages of chemical carcinogenesis in human beings Arsenic exposure is associated with G2/M cell cycle arrest and DNA aneuploidy in both cultured keratinocytes and AsBD lesions These cellular abnormalities relate to the p53 dysfunction induced by arsenic The characteristic clinical figures of arsenicinduced skin cancer are i occurrence on sunprotected areas of the body ii multiple and recrudescent lesions Both As and UVB are able to induce skin cancer Arsenic treatment enhances the cytotoxicity mutagenicity and clastogenicity of UV in mammalian cells Both As and UVB induce apoptosis in keratinocytes by caspase9 and caspase8 signaling respectively Combined UVB and As treatments resulted in the antiproliferative and proapoptotic effects by stimulating both caspase pathways in the keratinocytes UVB irradiation inhibited mutant p53 and ki67 expression as well as increased in the number of apoptotic cells in AsBD lesions which resulted in an inhibitory effect on proliferation AsUVB interaction provides a reasonable explanation for the rare occurrences of arsenical cancer in the sunexposed skin The multiple and recurrent skin lesions are associated with cellular immune dysfunction in chronic arsenism A decrease in peripheral CD4+ cells was noticed in the inhabitants of arsenic exposure areas There was a decrease in the number of Langerhans cells in AsBD lesion which results in an impaired immune function on the lesional sites Since CD4+ cells are the target cell affected by As the interaction between CD4+ cells and epidermal keratinocytes under As affection might be closely linked to the pathogenesis of multiple occurrence of arsenicinduced skin cancer In this review we provide and discuss the pathomechanisms of arsenic skin cancer and the relationship to its characteristic figures Such information is critical for understanding the molecular mechanism for arsenic carcinogenesis in other internal organs

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