Genetic Variants Associated with Arsenic Susceptibility: Study of Purine Nucleoside Phosphorylase, Arsenic (+3) Methyltransferase, and Glutathione
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            -Transferase Omega Genes

Chaudhuri, Sujata De; Ghosh, Pritha; Sarma, Nilendu; Majumdar, Papiya; Sau, Tanmoy Jyoti; Basu, Santanu; Roychoudhury, Susanta; Ray, Kunal; Giri, Ashok K.

doi:10.1289/ehp.10581

Cited by 94 publications

(66 citation statements)

References 30 publications

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“…(Vahter, 2002). With the exception of As V reduction to As III , which is catalyzed by purine nucleoside phosphorylase, these steps are catalyzed by glutathione S-transferases v1 and v2 (using glutathione as the reducing agent) and arsenic methyltransferase (using S-adenosylmethionine as the methyl donor) (De Chaudhuri et al, 2008) (Fig. 1).…”

Section: Introductionmentioning

confidence: 99%

Arsenic, Reactive Oxygen, and Endothelial Dysfunction

Ellinsworth

2015

J Pharmacol Exp Ther

102

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Human exposure to drinking water contaminated with arsenic is a serious global health concern and predisposes to cardiovascular disease states, such as hypertension, atherosclerosis, and microvascular disease. The most sensitive target of arsenic toxicity in the vasculature is the endothelium, and incubation of these cells with low concentrations of arsenite, a naturally occurring and highly toxic inorganic form of arsenic, rapidly induces reactive oxygen species (ROS) formation via activation of a specific NADPH oxidase (Nox2). Arsenite also induces ROS accumulation in vascular smooth muscle cells, but this is relatively delayed because, depending on the vessel from which they originate, these cells often lack Nox2 and/or its essential regulatory cytosolic subunits. The net effect of such activity is attenuation of endothelium-dependent conduit artery dilation via superoxide anion-mediated scavenging of nitric oxide (NO) and inhibition and downregulation of endothelial NO synthase, events that are temporally matched to the accumulation of oxidants across the vessel wall. By contrast, ROS induced by the more toxic organic trivalent arsenic metabolites (monomethylarsonous and dimethylarsinous acids) may originate from sources other than Nox2. As such, the mechanisms through which vascular oxidative stress develops in vivo under continuous exposure to all three of these potent arsenicals are unknown. This review is a comprehensive analysis of the mechanisms that mediate arsenic effects associated with Nox2 activation, ROS activity, and endothelial dysfunction, and also considers future avenues of research into what is a relatively poorly understood topic with major implications for human health.

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Section: Introductionmentioning

confidence: 99%

Arsenic, Reactive Oxygen, and Endothelial Dysfunction

Ellinsworth

2015

J Pharmacol Exp Ther

102

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“…Among the four candidate genes, distribution of three exonic polymorphisms, His 20His, Gly 51Ser, and Pro 57Pro of PNP was found to be associated with arsenicosis. Genotypes with minor alleles were significantly overrepresented in the case group: OR Z 1.69 (95% CI Z 1.08e2.66) for His 20His; OR Z 1.66 (95% CI Z 1.04e2.64) for Gly 51Ser; and OR Z 1.67 (95% CI Z 1.05e2.66) for Pro 57Pro.The results indicate that three PNP variants render participants susceptible toward developing arsenic-induced skin lesions [75].…”

Section: Genetic Polymorphismmentioning

confidence: 95%

Chronic arsenic toxicity: Studies in West Bengal, India

Mazumder¹,

Dasgupta

2011

The Kaohsiung J of Med Scie

177

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Chronic arsenic toxicity (arsenicosis) as a result of drinking arsenic-contaminated groundwater is a major environmental health hazard throughout the world, including India. A lot of research on health effects, including genotoxic effect of chronic arsenic toxicity in humans, have been carried out in West Bengal during the last 2 decades. A review of literature including information available from West Bengal has been made to characterize the problem. Scientific journals, monographs, and proceedings of conferences with regard to human health effects, including genotoxicity, of chronic arsenic toxicity have been reviewed. Pigmentation and keratosis are the specific skin diseases characteristic of chronic arsenic toxicity. However, in West Bengal, it was found to produce various systemic manifestations, such as chronic lung disease, characterized by chronic bronchitis, chronic obstructive and/or restrictive pulmonary disease, and bronchiectasis; liver diseases, such as non cirrhotic portal fibrosis; polyneuropathy; peripheral vascular disease; hypertension; nonpitting edema of feet/hands; conjunctival congestion; weakness; and anemia. High concentrations of arsenic, greater than or equal to 200 μg/L, during pregnancy were found to be associated with a sixfold increased risk for stillbirth. Cancers of skin, lung, and urinary bladder are the important cancers associated with this toxicity. Of the various genotoxic effects of arsenic in humans, chromosomal aberration and increased frequency of micronuclei in different cell types have been found to be significant. Various probable mechanisms have been incriminated to cause DNA damage because of chronic arsenic toxicity. The results of the study in West Bengal suggest that deficiency in DNA repair capacity, perturbation of methylation of promoter region of p53 and p16 genes, and genomic methylation alteration may be involved in arsenic-induced disease manifestation in humans. P53 polymorphism has been found to be associated with increased occurrence of arsenic-induced keratosis. Of the various genes involved in the regulation of arsenic metabolism, single-nucleotide polymorphisms of purine nucleoside phosphorylase, in one study, showed increased occurrence of arsenicosis.

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“…Again, screening of the entire coding region revealed only one exonic SNP (Met287Thr) in our population, with a heterozygosity of about 9%, similar to studies with African-American and white American populations. Thus the result (Table 1) depict that the individuals carrying these genotypes are showing an increased tendency of developing arsenic induced skin lesions and hence increased susceptibility towards arsenic toxicity (De Chaudhuri et al, 2008).…”

Section: Analysis Of Purine Nucleoside Phosphorylase (Pnp) and Arsenimentioning

confidence: 98%

Arsenic Induced Health Effects, Genetic Damage and Genetic Variants in the Population Exposed to Arsenic through Drinking Water in West Bengal

Banerjee¹,

Giri²

2014

Proceedings of the Indian National Science Academy

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Ar s e n i c i s a p o t e n t h u ma n c a r c i n o g e n , wh i c h a ffe c t s mi l l i o n s o f p e o p l e a r o u n d t h e wo r l d c a u s i n g d e l e t e r i o u s h e a l t h impacts including cancer and death. In India, West Bengal is the worst affected state where more than 26 million people are exposed chronically to arsenic by drinking heavily contaminated ground water. Several hypotheses have been associated wi t h a r s e n i c -i n d u c e d c a r c i n o g e n e s i s i n c l u d i n g c h r o mo s o ma l a b n o r ma l i t i e s , o x i d a t i v e s t r e s s , a l t e r e d D N A r e p a i r, p 5 3 gene suppression, gene amplification, transformation and altered growth factors leading to increased cell proliferation and carcinogenesis. In addition to that, it has been hypothesised that altered DNA methylation patterns might contribute to a r s e n i c -i n d u c e d c a r c i n o g e n e s i s . E v e n t h e n , t h e m e c h a n i s m s l e a d i n g t o a r s e n i c -i n d u c e d c a r c i n o g e n e s i s a r e p o o r l y u n d e r s t o o d . W e h a v e b e e n t r y i n g t o i d e n t i f y t h e c o n t e n d e r s t h a t c o n t r i b u t e t o a r s e n i c s u s c e p t i b i l i t y , t o xi c i t y a n d c a r c i n o g e n i c i t y i n t h e arsenic exposed rural population of West Bengal. In this article, attempts have been made to summarise the work that we have carried out so far in the said human population exposed to arsenic through drinking water.

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Genetic Variants Associated with Arsenic Susceptibility: Study of Purine Nucleoside Phosphorylase, Arsenic (+3) Methyltransferase, and Glutathione S -Transferase Omega Genes

Cited by 94 publications

References 30 publications

Arsenic, Reactive Oxygen, and Endothelial Dysfunction

Arsenic, Reactive Oxygen, and Endothelial Dysfunction

Chronic arsenic toxicity: Studies in West Bengal, India

Arsenic Induced Health Effects, Genetic Damage and Genetic Variants in the Population Exposed to Arsenic through Drinking Water in West Bengal

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