Enhanced frequency of micronuclei in individuals exposed to arsenic through drinking water in West Bengal, India

Basu, Arindam; Mahata, Julie; Roy, A. K.; Sarkar, J.N.; Poddar, G.; Nandy, Ashoke; Sarkar, Prasanta Kumar; Dutta, Puspendu; Banerjee, A.; Das, Madhusudan; Ray, Kunal; Roychaudhury, S.; Natarajan, A.T.; Nilsson, Robert; Giri, Ashok K.

doi:10.1016/s1383-5718(02)00014-1

Cited by 92 publications

(40 citation statements)

References 26 publications

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“…Therefore at low dose, arsenite acts as an aneugen, but at high dose it acts as a clastogen [15]. An increased frequency of MN has been detected in exfoliated bladder cells, buccal cells, sputum cells and lymphocytes from arsenic-exposed population [41][42][43]. Chien et al reported that arsenite induced an increased frequency of MN in HaCaT cells which was associated with tumorigenicity in nude mice [44].…”

Section: Genotoxicitymentioning

confidence: 99%

Arsenic Carcinogenesis in the Skin

2006

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SummaryChronic arsenic poisoning is a world public health issue. Long-term 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 arsenic-induced skin cancers are Bowen's disease (carcinoma in situ), basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Arsenic-induced Bowen's disease (As-BD) is able to transform into invasive BCC and SCC. Individuals with As-BD are considered for more aggressive cancer screening in the lung and urinary bladder. As-BD 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 As-BD lesions. These cellular abnormalities relate to the p53 dysfunction induced by arsenic. The characteristic clinical figures of arsenic-induced skin cancer are: (i) occurrence on sun-protected 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 caspase-9 and caspase-8 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 ki-67 expression, as well as increased in the number of apoptotic cells in As-BD lesions which resulted in an inhibitory effect on proliferation. As-UVB interaction provides a reasonable explanation for the rare occurrences of arsenical cancer in the sun-exposed 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 As-BD 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 arsenic-induced skin cancer. In this

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Section: Genotoxicitymentioning

confidence: 99%

Arsenic Carcinogenesis in the Skin

2006

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“…Arsenite exposure induced micronuclei (MN) formation [38], which indicates cellular response to DNA damages. An increased frequency of MN was also detected in exfoliated bladder cells, buccal cells, and lymphocytes from arsenic-exposed humans [39][40][41]. Chien et al showed that arsenite results in tumorigenicity of HaCaT cells in nude mice by increased frequency of MN [42].…”

Section: Proposed Mechanisms Of Action In Arsenical Carcinogenesismentioning

confidence: 99%

Mechanisms and Immune Dysregulation in Arsenic Skin Carcinogenesis

Lee

Liao²,

Yu³

2010

JCT

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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.

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“…Bladder cancer has been associated with exposure to chemicals present in environmental and occupational settings, such as arsenic in drinking water (Basu et al, 2002), 4,4'-methylenebis-(2-chloroaniline) used in manufacturing of wear-resistant polyurethane products (Murray and Edwards, 1999) or occupational exposure as a painter (Straif et al, 2007). In particular, exposure to polycyclic aromatic hydrocarbons (PAHs) present in coal gasification and aluminium production industries, in mixtures of coal-tar pitch, coal tar and asphalt (Straif et al, 2005), as well as in tobacco smoke (Burgaz et al, 1995;DeMarini, 2004), reveal a statistically significant excess risk of bladder cancer.…”

Section: Introductionmentioning

confidence: 99%

“…Following arsenic exposure through drinking of contaminated water, an increase MNu frequency was observed in populations living in many countries, including India, Chile, China and United States (Basu et al, 2002;Biggs et al, 1997;Tian et al, 2001;Warner et al, 1994). Also, a follow-up study revealed a decreased frequency of MNu in individuals who lowered their intake of water contaminated with arsenic (Moore et al, 1997a), suggesting the usefulness of this urinary assay in environmental health.…”

Section: Introductionmentioning

confidence: 99%

Optimizing urothelial cell preparation for the human urinary micronucleus assay

Fortin

Anghel

Brochu

et al. 2010

Toxicology in Vitro

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Biological monitoring of early genotoxic effects in urothelial cells using the urinary micronucleus (MNu) assay is promising for early detection of cancer, such as bladder carcinoma. But many problems are encountered, the major being the poorly differential staining of cells, particularly in women having an important amount of squamous cells. We have optimized the protocol and obtained a differential staining of the cell types present in urine on 10 subjects. Following Carnoy I fixation and Papanicolaou staining, urothelial cells were blue while most squamous cells were pink. This differential staining allowed for optimization of the MNu assay on a single urine void, for both females and males. Even if our MNu means were comparable to the literature, the great variation in reported MNu results could reside in the ability of scorers to distinguish correctly between urothelial and squamous cells. When monitoring exposed populations, this erroneous distinction could largely influence the results, even more in women's urine samples. Given a situation where exposure would not increase micronuclei frequency in vaginal squamous cells, their erroneous analysis in the MNu assay could mask an early genotoxic effect. Therefore, as transitional cell carcinoma of the bladder originates from transformed urothelial cells, restricting micronuclei analysis to urothelial cells could yield a more precise estimate of cancer risk in exposed populations. Moreover, it is hoped that the improvements proposed in this paper will allow for an easier implementation of the MNu assay in various set-ups and enhance its specificity, since MNu are considered a suitable biomarker.

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Enhanced frequency of micronuclei in individuals exposed to arsenic through drinking water in West Bengal, India

Cited by 92 publications

References 26 publications

Arsenic Carcinogenesis in the Skin

Arsenic Carcinogenesis in the Skin

Mechanisms and Immune Dysregulation in Arsenic Skin Carcinogenesis

Optimizing urothelial cell preparation for the human urinary micronucleus assay

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