Association of specific p53 polymorphisms with keratosis in individuals exposed to arsenic through drinking water in West Bengal, India

Chaudhuri, Sujata De; Mahata, Julie; Das, Jayanta; Mukherjee, Angshuman; Ghosh, Prasenjit; Sau, Tanmoy Jyoti; Mondal, Lakshmikanta; Basu, Santanu; Giri, Ashok K.; Roychoudhury, Susanta

doi:10.1016/j.mrfmmm.2006.06.014

Cited by 39 publications

(21 citation statements)

References 45 publications

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“…For the p53 16 bp duplication allele at intron 3, however, we did not observe any positive results. Several studies reported functional differences in genotypes at intron 3 and intron 6 polymorphisms of p53 gene (30,36,39,40). One study reported a lower repair capacity of lymphoblastoid cell lines that harbor less frequent alleles of 16 bp duplication at intron 3 and a G > A polymorphism at intron 6 (30).…”

Section: Discussionmentioning

confidence: 99%

Genetic Polymorphisms, Messenger RNA Expression of p53, p21, and CCND1, and Possible Links with Chromosomal Aberrations in Chinese Vinyl Chloride–Exposed Workers

Qiu

Wang

et al. 2008

Cancer Epidemiology, Biomarkers &Amp; Prevention

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This study explores the relationship between genetic polymorphisms of p53, p21, and CCND1, and the susceptibility of chromosomal damage induced by vinyl chloride monomer (CH 2 = CHCl, VCM). Besides gene polymorphisms, we detected the mRNA expression of p53, p21, and CCND1 in VCM-exposed workers and in a control group. One hundred and eighty-three workers occupationally exposed to VCM were investigated. Chromosome damage in peripheral lymphocyte was measured by cytokinesis-block micronucleus assay. The PCR-restriction fragment length polymorphism technique was applied to detect polymorphisms of p53, p21 (exon 2 and exon 3), and CCND1 genes (exon 4). The quantity of gene mRNA expression was detected by realtime PCR (SYBR Green I). Taking into account the effects of genetic polymorphisms, as well as demographic and habitual factors, Poisson regression analysis showed that the risk of chromosomal damage induced by VCM for individuals carrying the p53 intron 6 heterozygous and mutant homozygous genotype was 1.23 times larger (90% confidence interval, 1.01-1.51 P = 0.0814), compared with those carrying wild-type homozygous genotypes. The p53 exon 4, intron 3, and intron 6 haplotype pairs of MMM/WWW (M, mutation allele; W, wild allele), and MWM/WWW were associated with increased frequencies of micronuclei. The p53 mRNA expression of VCM-exposed workers was significantly lower than that of nonexposed workers, but p21 mRNA expression in VCM-exposed workers was significantly higher than that of nonexposed workers. Our findings suggest that the p53 intron 6 polymorphism is one of the factors that potentially influence the frequency of micronuclei induced by VCM. (Cancer Epidemiol Biomarkers Prev 2008;17(10):2578 -84)

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Section: Discussionmentioning

confidence: 99%

Genetic Polymorphisms, Messenger RNA Expression of p53, p21, and CCND1, and Possible Links with Chromosomal Aberrations in Chinese Vinyl Chloride–Exposed Workers

Qiu

Wang

et al. 2008

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…The deletion mutants that showed arsenic-sensitive phenotype were categorized based on the biological functions of the genes. The information on the biological functions for each of these genes was obtained from Saccharomyces Genome Database (SGD) 1 and Comprehensive Yeast Genome Database (CYGD). 2 Interaction analysis of the genes using PathwayAssist software.…”

Section: Discussionmentioning

confidence: 99%

“…Human exposure to arsenic poses a global health problem affecting millions of people worldwide (1,2). The situation has been described as ''humanity's biggest mass poisoning'' (3).…”

Section: Introductionmentioning

confidence: 99%

Genetic Determinants of Mitochondrial Response to Arsenic in YeastSaccharomyces cerevisiae

Vujcic

Shroff²,

Singh³

2007

Cancer Research

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We have used yeast Saccharomyces cerevisiae as a tool to identify the importance of mitochondrial processes involved in arsenic-induced carcinogenicity in humans. We screened 466 single-gene knockout strains of yeast S. cerevisiae known to be involved in biogenesis of mitochondria for sodium arsenite (AsIII) and sodium arsenate (AsV) sensitivity. We identified 72 arsenite-sensitive and 81 arsenate-sensitive mutants. We categorized the identified mutants based on the various mitochondrial processes, including nucleic acid metabolism, oxidative phosphorylation, protein synthesis, and vacuolar acidification. We have identified 65 human orthologues to proteins involved in arsenite sensitivity and 3 human orthologues to arsenite resistance. Furthermore, 23 human orthologues to arsenate sensitivity and 20 human orthologues to arsenate-resistant proteins, including MSH3, COX10, GCSH, PPOX, and MTHFD1, were also identified. Using PathwayAssist software, we did cellular network analysis between identified mitochondrial proteins. Three types of interactions, (a) protein-protein interactions, (b) common transcriptional regulators, and (c) common target genes, were identified. We found that RTG (retrograde) genes involved in mitochondria-to-nucleus signaling regulate both arsenite sensitivity and resistance. Furthermore, our study revealed that ABF1, a multifunctional transcriptional factor, regulates genes involved in both arsenite and arsenate sensitivity and resistance. However, REB1 and RAP1 transcriptional regulators were common to only arsenate-and arsenite-sensitive genes, respectively. These studies indicate that multiple pathways involved in mitochondrial biogenesis protect yeast S. cerevisiae from arsenic-induced toxicity. Together, our studies suggest that evolutionary conserved mitochondrial networks identified in yeast S. cerevisiae must play an important role in arsenic-induced carcinogenesis in humans.

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“…Arsenic in drinking water and its health effects Ghosh et al toxicity and paves the way for gene-environment studies that are already being preformed by our group (De Chaudhuri et al, 2006;Ghosh et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Comparison of health effects between individuals with and without skin lesions in the population exposed to arsenic through drinking water in West Bengal, India

Ghosh

Banerjee

Chaudhuri

et al. 2006

J Expo Sci Environ Epidemiol

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A study was conducted to explore the effect of arsenic causing conjunctivitis, neuropathy and respiratory illness in individuals, with or without skin lesions, as a result of exposure through drinking water, contaminated with arsenic to similar extent. Exposed study population belongs to the districts of North 24 Parganas and Nadia, West Bengal, India. A total of 725 exposed (373 with skin lesions and 352 without skin lesions) and 389 unexposed individuals were recruited as study participants. Participants were clinically examined and interviewed. Arsenic content in drinking water, urine, nail and hair was estimated. Individuals with skin lesion showed significant retention of arsenic in nail and hair and lower amount of urinary arsenic compared to the group without any skin lesion. Individuals with skin lesion also showed higher risk for conjunctivitis ((odd's ratio) OR: 7.33, 95% CI: 5.05-10.59), peripheral neuropathy (OR: 3.95, 95% CI: 2.61-5.93) and respiratory illness (OR: 4.86, 95% CI: 3.16-7.48) compared to the group without any skin lesion. The trend test for OR of the three diseases in three groups was found to be statistically significant. Again, individuals without skin lesion in the exposed group showed higher risk for conjunctivitis (OR: 4.66, 95% CI: 2.45-8.85), neuropathy (OR: 3.99, 95% CI: 1.95-8.09), and respiratory illness (OR: 3.21, 95% CI: 1.65-6.26) when compared to arsenic unexposed individuals. Although individuals with skin lesions were more susceptible to arsenicinduced toxicity, individuals without skin lesions were also subclinically affected and are also susceptible to arsenic-induced toxicity and carcinogenicity when compared to individuals not exposed to arsenic.

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Association of specific p53 polymorphisms with keratosis in individuals exposed to arsenic through drinking water in West Bengal, India

Cited by 39 publications

References 45 publications

Genetic Polymorphisms, Messenger RNA Expression of p53, p21, and CCND1, and Possible Links with Chromosomal Aberrations in Chinese Vinyl Chloride–Exposed Workers

Genetic Polymorphisms, Messenger RNA Expression of p53, p21, and CCND1, and Possible Links with Chromosomal Aberrations in Chinese Vinyl Chloride–Exposed Workers

Genetic Determinants of Mitochondrial Response to Arsenic in YeastSaccharomyces cerevisiae

Comparison of health effects between individuals with and without skin lesions in the population exposed to arsenic through drinking water in West Bengal, India

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