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Cancer Epidemiology, Biomarkers & Prevention
Cancer Epidemiology, Biomarkers & Prevention

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Associations between Arsenic Exposure and Global Posttranslational Histone Modifications among Adults in Bangladesh

Yana Chervona, Megan N. Hall, Adriana Arita, Fen Wu, Hong Sun, Hsiang-Chi Tseng, Eunus Ali, Mohammad Nasir Uddin, Xinhua Liu, Maria Antonietta Zoroddu, Mary V. Gamble and Max Costa
Yana Chervona
Authors' Affiliations: Department of Environmental Medicine, New York University School of Medicine; Columbia University Arsenic Project in Bangladesh; Departments of Epidemiology, Biostatistics, and Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York; and Department of Chemistry, University of Sassari, Sassari, Italy
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Megan N. Hall
Authors' Affiliations: Department of Environmental Medicine, New York University School of Medicine; Columbia University Arsenic Project in Bangladesh; Departments of Epidemiology, Biostatistics, and Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York; and Department of Chemistry, University of Sassari, Sassari, Italy
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Adriana Arita
Authors' Affiliations: Department of Environmental Medicine, New York University School of Medicine; Columbia University Arsenic Project in Bangladesh; Departments of Epidemiology, Biostatistics, and Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York; and Department of Chemistry, University of Sassari, Sassari, Italy
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Fen Wu
Authors' Affiliations: Department of Environmental Medicine, New York University School of Medicine; Columbia University Arsenic Project in Bangladesh; Departments of Epidemiology, Biostatistics, and Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York; and Department of Chemistry, University of Sassari, Sassari, Italy
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Hong Sun
Authors' Affiliations: Department of Environmental Medicine, New York University School of Medicine; Columbia University Arsenic Project in Bangladesh; Departments of Epidemiology, Biostatistics, and Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York; and Department of Chemistry, University of Sassari, Sassari, Italy
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Hsiang-Chi Tseng
Authors' Affiliations: Department of Environmental Medicine, New York University School of Medicine; Columbia University Arsenic Project in Bangladesh; Departments of Epidemiology, Biostatistics, and Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York; and Department of Chemistry, University of Sassari, Sassari, Italy
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Eunus Ali
Authors' Affiliations: Department of Environmental Medicine, New York University School of Medicine; Columbia University Arsenic Project in Bangladesh; Departments of Epidemiology, Biostatistics, and Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York; and Department of Chemistry, University of Sassari, Sassari, Italy
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Mohammad Nasir Uddin
Authors' Affiliations: Department of Environmental Medicine, New York University School of Medicine; Columbia University Arsenic Project in Bangladesh; Departments of Epidemiology, Biostatistics, and Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York; and Department of Chemistry, University of Sassari, Sassari, Italy
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Xinhua Liu
Authors' Affiliations: Department of Environmental Medicine, New York University School of Medicine; Columbia University Arsenic Project in Bangladesh; Departments of Epidemiology, Biostatistics, and Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York; and Department of Chemistry, University of Sassari, Sassari, Italy
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Maria Antonietta Zoroddu
Authors' Affiliations: Department of Environmental Medicine, New York University School of Medicine; Columbia University Arsenic Project in Bangladesh; Departments of Epidemiology, Biostatistics, and Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York; and Department of Chemistry, University of Sassari, Sassari, Italy
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Mary V. Gamble
Authors' Affiliations: Department of Environmental Medicine, New York University School of Medicine; Columbia University Arsenic Project in Bangladesh; Departments of Epidemiology, Biostatistics, and Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York; and Department of Chemistry, University of Sassari, Sassari, Italy
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Max Costa
Authors' Affiliations: Department of Environmental Medicine, New York University School of Medicine; Columbia University Arsenic Project in Bangladesh; Departments of Epidemiology, Biostatistics, and Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York; and Department of Chemistry, University of Sassari, Sassari, Italy
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DOI: 10.1158/1055-9965.EPI-12-0833 Published December 2012
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Abstract

Background: Exposure to arsenic (As) is associated with an increased risk of several cancers as well as cardiovascular disease, and childhood neuro-developmental deficits. Arsenic compounds are weakly mutagenic, alter gene expression and posttranslational histone modifications (PTHMs) in vitro.

Methods: Water and urinary As concentrations as well as global levels of histone 3 lysine 9 di-methylation and acetylation (H3K9me2 and H3K9ac), histone 3 lysine 27 tri-methylation and acetylation (H3K27me3 and H3K27ac), histone 3 lysine 18 acetylation (H3K18ac), and histone 3 lysine 4 trimethylation (H3K4me3) were measured in peripheral blood mononuclear cells (PBMC) from a subset of participants (N = 40) of a folate clinical trial in Bangladesh (FACT study).

Results: Total urinary As (uAs) was positively correlated with H3K9me2 (r = 0.36, P = 0.02) and inversely with H3K9ac (r = −0.47, P = 0.002). The associations between As and other PTHMs differed in a gender-dependent manner. Water As (wAs) was positively correlated with H3K4me3 (r = 0.45, P = 0.05) and H3K27me3 (r = 0.50, P = 0.03) among females and negatively correlated among males (H3K4me3: r = −0.44, P = 0.05; H3K27me3: r = −0.34, P = 0.14). Conversely, wAs was inversely associated with H3K27ac among females (r = −0.44, P = 0.05) and positively associated among males (r = 0.29, P = 0.21). A similar pattern was observed for H3K18ac (females: r = −0.22, P = 0.36; males: r = 0.27, P = 0.24).

Conclusion: Exposure to As is associated with alterations of global PTHMs; gender-specific patterns of association were observed between As exposure and several histone marks.

Impact: These findings contribute to the growing body of evidence linking As exposure to epigenetic dysregulation, which may play a role in the pathogenesis of As toxicity. Cancer Epidemiol Biomarkers Prev; 21(12); 2252–60. ©2012 AACR.

  • Received July 16, 2012.
  • Revision received September 25, 2012.
  • Accepted October 1, 2012.
  • ©2012 American Association for Cancer Research.
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Cancer Epidemiology Biomarkers & Prevention: 21 (12)
December 2012
Volume 21, Issue 12
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Associations between Arsenic Exposure and Global Posttranslational Histone Modifications among Adults in Bangladesh
Yana Chervona, Megan N. Hall, Adriana Arita, Fen Wu, Hong Sun, Hsiang-Chi Tseng, Eunus Ali, Mohammad Nasir Uddin, Xinhua Liu, Maria Antonietta Zoroddu, Mary V. Gamble and Max Costa
Cancer Epidemiol Biomarkers Prev December 1 2012 (21) (12) 2252-2260; DOI: 10.1158/1055-9965.EPI-12-0833

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Associations between Arsenic Exposure and Global Posttranslational Histone Modifications among Adults in Bangladesh
Yana Chervona, Megan N. Hall, Adriana Arita, Fen Wu, Hong Sun, Hsiang-Chi Tseng, Eunus Ali, Mohammad Nasir Uddin, Xinhua Liu, Maria Antonietta Zoroddu, Mary V. Gamble and Max Costa
Cancer Epidemiol Biomarkers Prev December 1 2012 (21) (12) 2252-2260; DOI: 10.1158/1055-9965.EPI-12-0833
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