Archived Publication Announcements

January 1 2015

Association of Epigenetic Modifications with Arsenic Toxicity Point to Potential Pathways for Intervention

Dr. Maria Argos along with other Columbia SRP scientists Mary Gamble, Kristin Harper, Faruque Parvez, Joseph Graziano, and Habibul Ahsan studied the association between arsenic exposure and epigenome-wide white blood cell DNA methylation in a population of 400 Bangladeshi adults. Arsenic exposure was measured in terms of blood and urinary total arsenic concentrations. The study “Gene-Specific Differential DNA Methylation and Chronic Arsenic Exposure in an Epigenome-Wide Association Study of Adults in Bangladesh” was published in the January issue of Environmental Health Perspectives. The authors concluded that there are significant associations between arsenic exposure and gene-specific white blood cell DNA methylation. Thus, epigenetic modifications may be key to arsenic toxicity. Details from this study reveal “specific differentially methylated loci” and, thus, may help target key pathways for future interventions.

Argos M, Chen L, Jasmine F, Tong L, Pierce BL, Roy S, Paul-Brutus R, Gamble MV, Harper KN, Parvez F, Rahman M, Rakibuz-Zaman M, Slavkovich V, Baron JA, Graziano JH, Kibriya MG, Ahsan H.  Gene-specific differential DNA methylation and chronic arsenic exposure in an epigenome-wide association study of adults in Bangladesh.  Environ Health Perspect 2015 Jan; 123(1):64-71.  PMCID: PMC4286273. Doi: 10.1289/ehp.1307884


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September 25 2014

Study at Vineland NJ SF Site Indicates Oxalic Acid Speeds up Release and Removal of Arsenic

Karen Wovkulich with other Columbia SRP scientists recently published an online version of their paper “In situ oxalic acid injection to accelerate arsenic remediation at a superfund site in New Jersey” in Environmental Chemistry. Using a forced gradient approach in this pilot-scale field study at the Vineland Superfund site in NJ, they tested whether adding chemicals to the contaminated aquifer would increase arsenic release and, thus, boost the efficiency of pump and treat remediation. Their findings indicate that adding oxalic acid substantially speeds up the release and removal of arsenic. If this approach could be scaled up to an entire site successfully, then it has the potential to reduce the time that it takes to cleanup sites contaminated with arsenic compared to traditional pump and treat approached. The online peer-reviewed and edited version is available now. The final publication will appear in a later issue of the journal.

Preferred citation:
Wovkulich K, Stute M, Mailloux BJ, Keimowitz AR, Ross J, Bostick B, Sun J, and Chillrud SN. In situ oxalic acid injection to accelerate arsenic remediation at a superfund site in New Jersey. Online Early, Environ. Chem. 2014.

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May 26 2014

Norm, Ability, and Attitude Barriers Impede Testing for Arsenic in Maine Private Wells

On May 26, 2014, the journal Science of the Total Environment published online a second paper this year by Columbia's Community Engagement Core scientists Sara Flanagan and Yan Zheng  and study partner Robert Marvinney from the Maine Geological Survey. The paper “Influences on domestic well water testing behavior in a Central Maine area with frequent groundwater arsenic occurrence" analyzes the results from a 2013 household survey responses from over 500 residents of 13 towns in Central Maine. The survey gathers information on the population's well water testing practices and key behaviors which influence testing for arsenic in an area with high well-water dependency and naturally occurring groundwater arsenic.

Whether households tested for arsenic is significantly associated with knowing or believing the following: 1) extended exposure to arsenic increases related health risks, 2) contact information for well-water testing, 3) testing does not take too much time, and 4) neighbors regularly test their water. However, the study also found that well owners often believe that they are at lower risk of arsenic exposure than their neighbors.

The paper concludes that households with private wells in areas with high concentrations of arsenic may not be testing for arsenic due to a combination of norm, ability, and attitude factors and barriers.

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April 13 2014

Factors Influencing Homeowner Response to Arsenic in Private Drinking Wells

Columbia's Community Engagement Core scientists Sara Flanagan, Qiang Yang, and Yan Zheng collaborating with Robert Marvinney and Robert Johnston of the Maine Geological Survey co-authored the paper, "Dissemination of well water arsenic results to homeowners in Central Maine: Influences on mitigation behavior and continued risksfor exposure". The paper is available online as of April 13th and in press with the journal, Science of the Total Environment.

The researchers have conducted a survey in central Maine of 386 households who were notified 3-7 years earlier that their well water contained arsenic (As) above 10 μg/L. The follow-up survey found that 43% of the households had installed water treatment systems, an additional 30% took other protective actions such as drinking bottled water, and the remaining 27% did not take action. This study looks at socio-demographic and psychological factors that may have influenced which actions/non-actions were taken in response to receiving As test results. Risk perception that the untreated water is not safe to drink and the belief that reducing the water As would increase home value were identified as significant predictors of having taken protective action for As; among those that did act on test results, socioeconomic factors and confidence in one's ability to maintain a treatment system influenced the decision of whether to install a home treatment system or to avoid drinking from the well. Water samples collected from the tap in a subset of these households with treatment systems in place revealed that treatment failure and continued As exposure is a risk even when a homeowner has taken the protective action to install a system.

Suggested citation:

Flanagan, S. V., Marvinney, R. G., Johnston, R. A., Yang, Q., Zheng, Y. Dissemination of well water arsenic results to homeowners in Central Maine: Influences on mitigation behavior and continued risks for exposure. Science of The Total Environment. In Press, Available online 13 April 2014.

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April 1 2014

Water Arsenic >= 5 mug/L pose possible threat to children

Environmental Health has published in its April 2014 edition the Columbia SRP paper,  "A cross-sectional study of well water arsenic and child IQ in Maine schoolchildren." CU SRP Project 2 scientist Gail Wasserman is the lead author. Her Columbia collaborators include Xinhua Liu, Nancy J LoIacono, Jennie Kline, Pam Factor-Litvak, Alexander van Geen, Jacob L Mey, Diane Levy, and Joseph H Graziano. Richard Abramson formerly with Readfield ME Public Schools and Amy Schwartz at the University of New Hampshire also contributed to this paper.

The authors start with a description of past studies. Earlier research by the CU SRP team focused on dose-dependent adverse associations between consumption of arsenic (As)- contaminated water from household wells and intellectual function in young Bangladeshi children. Their  initial work with 6- and 10-year olds, after adjustment for social factors related to intellectual function, indicated that water arsenic concentration (WAs) was significantly negatively related to WPPSI-III and WISC-III Performance (nonverbal ability) scores, but, in most instances, not to other components of intelligence, such as Verbal scores.  A more recent study of Bangladeshi 9-10 year olds, resulted in marginally significant associations between WAs and both Verbal Comprehension and Working Memory scores from the WISC-IV, after adjustments for socio-demographic features and for co-occurring exposure to manganese in drinking wate.  Water Arsenic was unrelated to other aspects of intellectual functioning. These and other studies in different populations have suggested that As exposure may affect early development. However, there has been little consistency in the specific components of child intelligence most affected.

The CU SRP study described in this paper included 272 childrent in grades 3-5 in 3 Maine public school districts. It examined associations between drinking water Arsenic and intelligence as measured by the WISC-IV test. The findings suggest that levels of Water Arsenic equal or greater than 5 mug/L, levels, which are below EPA national standards and occur frequently in some US regions, could pose a threat to child development.


Wasserman Gail A, Liu  Xinhua, LoIacono Nancy J, Kline Jennie, Factor-Litvak  Pam, van Geen  Alexander, Mey Jacob L, Levy  Diane, Abramson  Richard, Schwartz Amy, Graziano Joseph H. A cross-sectional study of well water arsenic and child IQ in Maine schoolchildren. Environmental Health 2014, 13:23 (1 April 2014). DOI: 10.1186/1476-069X-13-23

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March 5 2014

Additional evidence that nutritional status may explain differences in susceptibility to arsenic toxicity

Caitlin Howe, Columbia SRP student with Project 3, is the lead author of the upcoming paper, "Folate and Cobalamin Modify Associations between S-adenosylmethionine and Methylated Arsenic Metabolites in Arsenic-Exposed Bangladeshi Adults" that will appear in the May 2014 publication of the Journal of Nutrition. Co-authors include Columbia SRP student alumnae and scientists as well as collaborators from Columbia University Arsenic Project in Bangladesh. The key findings provide additional evidence that nutritional status may explain some differences among individuals in arsenic metabolism and, thus, susceptibility to arsenic toxicity. The paper is currently available online. Please see the link below.

Suggested citation:

Howe CG, Niedzwiecki MM, Hall MN, Liu X, Ilievski V, Slavkovich V, Alam S, Siddique AB, Graziano JH,4 and Gamble MV. Folate and Cobalamin Modify Associations between S-adenosylmethionine and Methylated Arsenic Metabolites in Arsenic-Exposed Bangladeshi Adults J. Nutr. May 2014 jn.113.188789; first published online March 5, 2014. doi:10.3945/jn.113.188789.

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September 11 2013

Nature publication: Retardation of arsenic transport through a Pleistocene aquifer


Nature published on September 11, 2013 a paper by CU SRP scientists Alexander van Geen, Benjamin Bostik, Kathleen Radloff, Zahid Aziz, Jacob L. Mey along with several of their collaborators on "Retardation of arsenic transport through a Pleistocene aquifer". Here they present findings from their study on the contamination of a Pleistocene aquifer near Hanoi, Vietnam. Their study reveals that "changes in groundwater flow conditions and the redox state of the aquifer sands induced by groundwater pumping caused the lateral intrusion of arsenic contamination more than 120 metres from a Holocene aquifer into a previously uncontaminated Pleistocene aquifer.We also find that arsenic adsorbs onto the aquifer sands and that there is a 16–20-fold retardation in the extent of the contamination relative to the reconstructed lateral movement of groundwater over the same period. Our findings suggest that arsenic contamination of Pleistocene aquifers in south and southeast Asia as a consequence of increasing levels of groundwater pumping may have been delayed by the retardation of arsenic transport."

The research presented here was fund by the US National Science Foundation and the NIEHS Superfund Research Program.

Additional authors include Vi Mai Lan, Nguyen-Ngoc Mai, Phu Dao Manh and Pham Hung Viet, of the Hanoi University of Science, Mason Stahl and Charles Harvey from MIT, Beth Weinman from Vanderbilt University along with researchers from Anchor QEA, Eawag Swiss Federal Institute of Aquatic Science and Technology,Institute of Geochemistry and Petrology, Swiss Federal Institute of Technology.

Suggested citation:
van Geen, A., Bostick, B., Thi Kim Trang, P., et al. 2013. Retardation of arsenic transport through a Pleistocene aquifer. Nature 501, 204–207 doi:10.1038/nature12444 (onine 12 September 2013).

Sponsored by: NIEHS Superfund Research Program and National Science Foundation
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July 1 2013

Blood glutathione redox status and global methylation of peripheral blood mononuclear cell DNA in Bangladeshi adults

The July issue of Epigenetics will include a paper by Mailman graduate student Megan Niedzwiecki and her Columbia SRP colleagues entitled “Blood glutathione redox status and global methylation of peripheral blood mononuclear cell DNA in Bangladeshi adults”. In this article, the researchers investigated the relationship between oxidative stress and DNA methylation in humans.   Oxidative stress and DNA methylation are metabolically linked:  depletion of glutathione (GSH), the body’s primary antioxidant, might lead to depletion of S-adenosylmethionine (SAM), the universal methyl donor for methylation reactions.  Additionally, many enzymes involved in DNA methylation show altered activity under oxidized cellular conditions., The Columbia SRP scientists tested the hypothesis that a more oxidized blood GSH redox status is associated with decreased global peripheral blood mononuclear cell (PBMC) DNA methylation in a sample of Bangladeshi adults. They found that a more oxidized blood GSH redox state was associated with decreased global DNA methylation, but blood SAM was not a mediator of this association. Future research should explore mechanisms through which cellular redox status might influence global DNA methylation as this may represent an important pathway leading towards both carcinogenic and non-carcinogenic mechanisms of action of arsenic. Given that redox status and DNA methylation are both potentially modifiable through nutritional and other interventions, a greater mechanistic understanding of these observations could ultimately have therapeutic implications.

Suggested citation:

Niedzwiecki M, Hall MN, Liu X, Oka J, Harper KN, Slavkovich V, Ilievski V, Levy D, van Geen A, Mey JL, Alam S, Siddique AB, Parvez F, Graziano JH, and Gamble MV. Blood glutathione redox status and global methylation of peripheral blood mononuclear cell DNA in Bangladeshi adults. Epigenetics 2013:8(7):730-738. Published Online: May 17, 2013.

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June 21 2013

EHP Publication: Chronic Arsenic Exposure and Blood Glutathione and Glutathione Disulfide Concentrations in Bangladeshi Adults

Exposure to arsenic (As) has been shown to deplete glutathione (GSH), the primary intracellular antioxidant, and induce oxidative stress in In vitro and rodent studies. Glutathione disulfide (GSSG) is produced after GSH donates an electron to reactive oxygen species.  The primary objective of this study was to test whether As exposure was associated with decreases in GSH and increases in GSSG, i.e., a more oxidized intracellular environment. Lead author Dr. Hall and her colleagues also investigated whether As exposure was associated with reductions in cysteine (Cys) and increases in cystine (CySS); Cys and CySS are the predominant thiol/disulfide redox couple found in human plasma.  The authors observed inverse associations of As exposure with GSH and Cyss, but no associations with GSSG and Cys and concluded that “The observed associations are consistent with the hypothesis that As may influence concentrations of GSH and other non-protein sulfhydryls through binding and irreversible loss in bile and/or possibly in urine.”

Hall MN, Niedzwiecki M, Liu X, Harper KN, Alam S, Slavkovich V, Ilievski V, Levy D, Siddique S, Parvez F, Mey JL, van Geen A, Graziano J, and Gamble MV. Chronic Arsenic Exposure and Blood Glutathione and Glutathione Disulfide Concentrations in Bangladeshi Adults. Environmental Health Perspectives Advance Publication: 21 June 2013.

June 10 2013

Two Potential Perils in Cancer Studies Involving DNA Methylation Array Analysis

The June publication of Cancer Epidemiology Biomarkers & Prevention features a paper by Kristin Harper, Bradilyn Peters, and Mary Gamble on “Batch Effects and pathway analysis: Two potential perils in cancer studies involving DNA methylation array analysis”. It includes some recent findings from their research under the Columbia Superfund Research Program’s Project 3, Impact of Nutrition on Arsenic-Induced Epigenetic Dysregulation.

DNA methylation microarrays have become an increasingly popular means of studying the role of epigenetics in cancer, although the methods used to analyze these arrays are still being developed and existing methods are not always widely disseminated among microarray users.

Harper, Peters, and Gamble investigated two problems likely to confront DNA methylation microarray users: (i) batch effects and (ii) the use of widely available pathway analysis software to analyze results. First, DNA taken from individuals exposed to low and high levels of drinking water arsenic were plated twice on Illumina's Infinium 450 K HumanMethylation Array, once in order of exposure and again following randomization. Second, they conducted simulations in which random CpG sites were drawn from the 450 K array and subjected to pathway analysis using Ingenuity's IPA software.

They concluded that the analyses illustrated the pitfalls of not properly controlling for chip-specific batch effects as well as using pathway analysis software created for gene expression arrays to analyze DNA methylation array data. The in silico pathway analysis experiment yielded spurious but significant findings due to over-representation of CpGs on the 450K array chip that were associated with genes involved in pathways linked to cancer, developmental disorders, cellular development, cell morphology, embryological development, and more.

Suggested citation

Harper KN, Peters BA, Gamble MV. Batch Effects and pathway analysis: Two potential perils in cancer studies involving DNA methylation array analysis. Cancer Epidemiol Biomarkers Prev 2013; 22(6); 1–9. Published OnlineFirst April 29, 2013; doi:10.1158/1055-9965.EPI-13-0114.

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