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Project Publications: Dartmouth College: Arsenic as an Endocrine Disrupter

Superfund Research Program

Arsenic as an Endocrine Disrupter

Project Leaders: Joshua W. Hamilton (Marine Biological Laboratory), Joshua W. Hamilton (Marine Biological Laboratory)
Grant Number: P42ES007373
Funding Period: 1995-2014

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  • Gosse JA, Taylor VF, Jackson BP, Hamilton JW, Bodwell J. 2014. Monomethylated trivalent arsenic species disrupt steroid receptor interactions with their DNA response elements at non-cytotoxic cellular concentrations. J Appl Toxicol 34(5):498-505. doi:10.1002/jat.2898 PMID:23765520 PMCID:PMC3884051


  • Kozul-Horvath CD, Zandbergen F, Jackson BP, Enelow RI, Hamilton JW. 2012. Effects of low-dose drinking water arsenic on mouse fetal and postnatal growth and development. PLoS One 7(5):e38249. doi:10.1371/journal.pone.0038249 PMID:22693606 PMCID:PMC3365045
  • Schwarzer A, Wolf B, Fisher JL, Schwaab T, Olek S, Baron U, Tomlinson CR, Seigne JD, Crosby NA, Gui J, Hampton TH, Fadul CE, Heaney JA, Ernstoff MS. 2012. Regulatory T-cells and associataed pathways in metastatic renal cell carcinoma (mRCC) patients undergoing DC-vaccination and cytokine-therapy. PLoS One 7(10):e46600. doi:10.1371/journal.pone.0046600 PMID:23118856 PMCID:PMC3485261


  • Fei DL, Li H, Kozul-Horvath CD, Black KE, Singh S, Gosse JA, DiRenzo J, Martin KA, Wang B, Hamilton JW, Karagas MR, Robbins DJ. 2010. Activation of Hedgehog signaling by the environmental toxicant arsenic may contribute to the etiology of arsenic-induced tumors. Cancer Res 70(5):1981-1988. doi:10.1158/0008-5472.CAN-09-2898 PMID:20179202 PMCID:PMC2831120


  • Barr FD, Krohmer LJ, Hamilton JW, Sheldon LA. 2009. Disruption of histone modification and CARM1 recruitment by arsenic represses transcription at glucocorticoid receptor-regulated promoters. PLoS One 4(8):e6766. doi:10.1371/journal.pone.0006766 PMID:19707557 PMCID:PMC2727952
  • Kozul-Horvath CD, Ely KH, Hamilton JW, Enelow RI. 2009. Low-dose arsenic compromises the immune response to influenza A infection in vivo. Environ Health Perspect 117(9):1441-1447. doi:10.1289/ehp.0900911 PMID:19750111 PMCID:PMC2737023
  • Kozul-Horvath CD, Hampton TH, Davey JC, Gosse JA, Nomikos AP, Eisenhauer PL, Weiss DJ, Thorpe JE, Ihnat MA, Hamilton JW. 2009. Chronic exposure to arsenic in the drinking water alters the expression of immune response genes in mouse lung. Environ Health Perspect 117(7):1108-1115. doi:10.1289/ehp.0800199 PMID:19654921 PMCID:PMC2717138


  • Andrew AS, Lantz RC, Rodgers, LS, Vaillancourt RR, Camenisch TD, Hays AM, Sollome JJ, Hamilton JW. 2008. Arsenic-induced decreases in the vascular matrix. Toxicol Pathol 36(6):805-817. doi:10.1177/0192623308323919 PMID:18812580 PMCID:PMC2875876
  • Davey JC, Nomikos AP, Wungjiranirun M, Sherman JR, Ingram L, Batki C, Lariviere JP, Hamilton JW. 2008. Arsenic as an endocrine disruptor: arsenic disrupts retinoic acid receptor-and thyroid hormone receptor-mediated gene regulation and thyroid hormone-mediated amphibian tail metamorphosis. Environ Health Perspect 116(2):165-172. doi:10.1289/ehp.10131 PMID:18288313 PMCID:PMC2235215
  • Kozul-Horvath CD, Nomikos AP, Hampton TH, Warnke L, Gosse JA, Davey JC, Thorpe JE, Jackson BP, Ihnat MA, Hamilton JW. 2008. Laboratory diet profoundly alters gene expression and confounds genomic analysis in mouse liver and lung. Chem Biol Interact 173(2):129-140. doi:10.1016/j.cbi.2008.02.008 PMID:18396267
  • Ye S, MacEachran DP, Hamilton JW, O'Toole GA, Stanton BA. 2008. Chemotoxicity of doxorubicin and surface expression of P-glycoprotein (MDR1) is regulated by the Pseudomonas aeruginosa toxin Cif. Am J Physiol Cell Physiol 295(3):C807-C818. doi:10.1152/ajpcell.00234.2008 PMID:18650266 PMCID:PMC2544439


  • Andrew AS, Bernardo V, Warnke L, Davey JC, Hampton TH, Mason RA, Thorpe JE, Ihnat MA, Hamilton JW. 2007. Exposure to arsenic at levels found inUS drinking water modifies expression in the mouse lung. Toxicol Sci 100(1):75-87. doi:10.1093/toxsci/kfm200 PMID:17682005
  • Bodwell J, Gosse JA, Hamilton JW, Davey JC. 2007. Arsenic as an endocrine disruptor: effects of arsenic on estrogen receptor-mediated gene expression in vivo and in cell culture. Toxicol Sci 98(1):75-86. doi:10.1093/toxsci/kfm013 PMID:17283378
  • Gosse JA, Hampton TH, Davey JC, Hamilton JW. 2007. Analysis and interpretation of toxicogenomic data: Biological responses to low, environmentally-relevant doses of toxicants. In: Toxicogenomics: An experimental tool for toxicity testing. (Sahu SC, ed).
  • Miller DS, Shaw JR, Stanton CR, Barnaby R, Karlson KH, Hamilton JW, Stanton BA. 2007. MRP2 and acquired tolerance to inorganic arsenic in the kidney of killifish (Fundulus heteroclitus). Toxicol Sci 97(1):103-110. doi:10.1093/toxsci/kfm030 PMID:17324950
  • Mustra DJ, Warren AJ, Wilcox DE, Hamilton JW. 2007. Preferential binding of human XPA to the mitomycin C-DNA interstrand crosslink and modulation by arsenic and cadmium. Chem Biol Interact 168(2):159-168. doi:10.1016/j.cbi.2007.04.004 PMID:17512921
  • Shaw JR, Gabor K, Hand E, Lankowski A, Durant L, Thibodeau R, Stanton CR, Barnaby R, Coutermarsh BA, Karlson KH, Sato J, Hamilton JW, Stanton BA. 2007. Role of glucocorticoid receptor in acclimation of killifish (Fundulus heteroclitus) to seawater and effects of arsenic. Am J Physiol Regul Integr Comp Physiol 292(2):R1052-R1060. doi:10.1152/ajpregu.00328.2006 PMID:17038445
  • Shaw JR, Jackson BP, Gabor K, Stanton S, Hamilton JW, Stanton BA. 2007. The influence of exposure history on arsenic accumulation and toxicity in the killifish, Fundulus heteroclitus. Environ Toxicol Chem 26:2704-2709. PMID:18020683


  • Andrew AS, Burgess JL, Meza MM, Demidenko E, Waugh MG, Hamilton JW, Karagas MR. 2006. Arsenic exposure is associated with decreased DNA repair in vitro and in individuals exposed to drinking water arsenic. Environ Health Perspect 114(8):1193-1198. PMID:16882524 PMCID:PMC1552016
  • Bodwell J, Gosse JA, Nomikos AP, Hamilton JW. 2006. Arsenic disruption of steroid receptor gene activation: complex dose-response effects are shared by several steroid receptors. Chem Res Toxicol 19(12):1619-1629. doi:10.1021/tx060122q PMID:17173375 PMCID:PMC2556599
  • DeCaprio AP, ed. 2006. Toxicologic Biomarkers. Informa Healthcare, New York, NY.
  • Hamilton JW. 2006. Toxicogenomic and Toxicoproteomic Approaches for Biomarkers. Chapter 11 in: Toxicologic Biomarkers. Informa Healthcare, New York, NY. pp.221-258.
  • Hamilton JW. 2006. Use of toxicogenomics to investigate the effects of toxicants in aquatic systems. In: Report on the CEISM Workshop, Marine Sciences and Public Health. Geneva, Switzerland.
  • Shaw JR, Dempsey TD, Chen CY, Hamilton JW, Folt CL. 2006. Comparative toxicity of cadmium, zinc, and mixtures of cadmium and zinc to daphnids. Environ Toxicol Chem 25(1):182-189. doi:10.1897/05-243R.1 PMID:16494240
  • Stanton CR, Thibodeau R, Lankowski A, Shaw JR, Hamilton JW, Stanton BA. 2006. Arsenic inhibits CFTR-mediated chloride secretion by killifish (Fundulus heteroclitus) opercular membrane. Cell Physiol Biochem 17(5-6):269-78. PMID:16791002
  • . 2006. Report on the CEISM Workshop, Marine Sciences and Public Health. Geneva, Switzerland.


  • Bates MN, Hamilton JW, LaKind JS, Langenberg P, O'Malley M, Snodgrass W. 2005. Workgroup report: biomonitoring study design, interpretation, and communication - lessons learned and path forward. Environ Health Perspect 113(11):1615-1621. PMID:16263520
  • Kamat CD, Green DE, Curilla S, Warnke L, Hamilton JW, Sturup S, Clark C, Ihnat MA. 2005. Role of HIF signaling on tumorigenesis in response to chronic low-dose arsenic administration. Toxicol Sci 86(2):248-257. doi:10.1093/toxsci/kfi190 PMID:15888669
  • Karagas MR, Park S, Warren AJ, Hamilton JW, Nelson HH, Mott LA, Kelsey KT. 2005. Gender, smoking, glutathione-S-transferase variants and bladder cancer incidence: a population-based study. Cancer Lett 219(1):63-69. doi:10.1016/j.canlet.2004.10.006 PMID:15694665
  • Maitra R, Hamilton JW. 2005. Arsenite regulates cystic fibrosis transmembrane conductance regulator and P-glycoprotein: evidence of pathway independence. Cell Physiol Biochem 16(1-3):109-118. doi:10.1159/000087737 PMID:16121039


  • Bodwell J, Kingsley LA, Hamilton JW. 2004. Arsenic at very low concentrations alters glucocorticoid receptor (GR)-mediated gene activation but not GR-mediated gene repression: complex dose-response effects are closely correlated with levels of activated GR and require a functional GR DNA binding domain. Chem Res Toxicol 17(8):1064-1076. PMID:15310238


  • Andrew AS, Karagas MR, Hamilton JW. 2003. Decreased DNA repair gene expression among individuals exposed to arsenic in United States drinking water. Int J Cancer 104(3):263-268. PMID:12569548
  • Andrew AS, Karagas MR, Klei L, Hamilton JW. 2003. Drinking water arsenic exposure is associated with decreased DNA repair gene expression. Toxicol Sci 72(S1):184.
  • Andrew AS, Warren AJ, Barchowsky A, Temple KA, Klei L, Soucy NV, O'Hara KA, Hamilton JW. 2003. Genomic and proteomic profiling of responses to toxic metals in human lung cells. Environ Health Perspect 111(6):825-838. PMID:12760830
  • Hamilton JW. 2003. Mechanism of hexavalent chromium (Cr(VI)) toxicity and carcinogenicity. Toxicol Sci 72(1):58.
  • Hamilton JW, Bodwell J, Kingsley LA, Barnet CS, Davey JC. 2003. Arsenic alters hormone-mediated positive, but not negative, regulatory effects of steroid receptors. Toxicol Sci 72(S1):16.
  • Shaw JR, Davey JC, Hamilton JW. 2003. Silver inhibits estrogen mediated gene transcription. In: Proceedings of the 24th Annual Meeting of the Society of Envirnmental Toxicology and Chemistry (SETAC), November 12, 2003. Austin, TX.
  • Zheng H, Wang X, Warren AJ, Legerski RJ, Nairn RS, Hamilton JW. 2003. Nucleotide excision repair- and polymerase -mediated error-prone removal of mitomycin C interstrand cross-links. Mol Cell Biochem 23(2):754-761. PMID:12509472


  • Andrew AS, Warren AJ, Temple KA, Hamilton JW. 2002. Differential effects of arsenic, chromium, cadmium, nickel and mitomycin C on gene expression as measured by DNA microarray. Toxicol Sci 66(S1):116.
  • Hamilton JW, Bodwell J, Kaltreider RC, Davis AM, Davey JC, Kingsley LA, Lariviere JP. 2002. Arsenic is an endocrine disruptor, blocking hormone-mediated gene regulation by the estrogen and glucocorticoid receptors in vivo. Toxicol Sci 66(S1):85.
  • Soucy NV, Barchowsky A, Klei L, Hamilton JW, Ihnat MA. 2002. Potential cellular mechanisms for arsenite-induced vascular diseases. Toxicol Sci 66(S1):86.
  • Wolf KK, Davis XM, Kaltreider RC, Davey JC, Lariviere JP, Hamilton JW. 2002. Chromium(III) and chromium(VI) stimulate cAMP-mediated cell signaling in cell culture and in vivo. Toxicol Sci 66(S1):32.


  • Hamilton JW, Davis AM, Kaltreider RC. 2001. Chromium(VI) alters glucocorticoid receptor (GR)-dependent and cAMP-dependent gene expression through a chromium(III)-sensitive, cAMP-mediated pathway. Toxicol Sci 60(S1):316.
  • Hamilton JW, Maitra R. 2001. The model anthracycline, doxorubicin, increases functional cell surface expression of DF508-CFTR protein by altering its structure and biogenesis. Pediatr Pulmonol 32(S22):256-281.
  • Kaltreider RC, Davis AM, Lariviere JP, Hamilton JW. 2001. Arsenic alters the function of the glucocorticoid receptor as a transcription factor. Environ Health Perspect 109(3):245-251. PMID:11333185
  • Maitra R, Halpin PA, Karlson KH, Page RL, Paik DY, Leavitt MO, Moyer BD, Stanton BA, Hamilton JW. 2001. Differential effects of mitomycin C and doxorubicin on P-glycoprotein expression. Biochem J 355(Pt3):617-624. PMID:11311122
  • Maitra R, Shaw CM, Stanton BA, Hamilton JW. 2001. Functional enhancement of CFTR expression by mitomycin C. Cell Physiol Biochem 11(2):93-98. doi:10.1159/000047796 PMID:11275687
  • Maitra R, Shaw CM, Stanton BA, Hamilton JW. 2001. Increased functional cell surface expression of CFTR and DeltaF508-CFTR by the anthracycline doxorubicin. Am J Physiol Cell Physiol 280(5):C1031-C1037. PMID:11287314
  • Mustra DJ, Warren AJ, Hamilton JW. 2001. Preferential binding of human full length XPA and the minimal DNA binding domain (XPA-MF122) with the mitomycin C-DNA interstrand crosslink. Biochemistry 40(24):7158-7164. PMID:11401562
  • Sillett KS, Chen CY, Folt CL, Hamilton JW. 2001. Using differential display RT-PCR to identify cadmium responsive genes in Daphnia pulex. In: Proceedings of the 22nd Annual Meeting of the Society of Environmental Toxicology and Chemistry (SETAC), November 11-15, 2001. Baltimore, MD.
  • Warren AJ, Mustra DJ, Hamilton JW. 2001. Detection of mitomycin C-DNA adducts in human breast cancer cells grown in culture, as xenografted tumors in nude mice, and in biopsies of human breast cancer patient tumors as determined by (32)P-postlabeling. Clin Cancer Res 7(4):1033-1042. PMID:11309355


  • Hamilton JW, Kaltreider RC, Davis AM, Green RA. 2000. Arsenic(III) and chromium(VI) alter glucocorticoid receptor (GR) function and GR-dependent gene regulation. Metal Ions in Biology and Medicine 6:66-68.
  • Kaltreider RC, Davis AM, Green RA, Hamilton JW. 2000. Arsenic(III)-induced alterations in glucocorticoid receptor (GR) function and correlation with alterations in GR-dependent gene expression. Chapter 41in: Proceedings of the 91st Annual Meeting of American Association for Cancer Research Annual Meeting, 2000. San Diego, CA. pp.506.
  • Warren AJ, Hamilton JW. 2000. Metal-induced alterations inecpression of nucleotide excision repair genes. Chapter 41in: Proceedings of the 91st Annual Meeting of American Association for Cancer Research Annual Meeting, 2000. San Diego, CA. pp.177.


  • Ihnat MA, Nervi AM, Anthony SP, Kaltreider RC, Warren AJ, Pesce CA, Davis SA, Lariviere JP, Hamilton JW. 1999. Effects of mitomycin C and carboplatin pre-treatment on multidrug resistance-associated P-glycoprotein expression and on subsequent suppression of tumor growth by doxorubicin and paclitaxel in human metastatic breast cancer xenografted nude mice. Oncol Res 11:303-310.
  • Kaltreider RC, Pesce CA, Ihnat MA, Lariviere JP, Hamilton JW. 1999. Differential effects of arsenic(III) and chromium(VI) on nuclear transcription factor binding. Mol Carcinog 25(3):219-229. PMID:10411148
  • Raha A, Hamilton JW, Bresnick E. 1999. The existence of the 4S polycyclic aromatic hydrocarbon-protein binding in 14-day-old chick embryo liver. Toxicol Appl Pharmacol 158:1-8. PMID:10387926
  • Yuann JP, Liu KJ, Hamilton JW, Wetterhahn KE. 1999. In vivo effects of ascorbate and glutathione on chromium uptake, formation of chromium(V), chromium-DNA binding and 8-OH-dG levels in liver and kidney of Ostegenic Disorder Shionogi (ODS) rats following treatment with chromium(VI). Carcinogenesis 20:1267-1275. PMID:10383900


  • Bentivegna CS, Ihnat MA, Baptiste NS, Hamilton JW. 1998. Developmental regulation of the 3 methylcholanthrene- and dioxin-inducible CYP1A5 gene in chick embryo liver in vivo. Toxicol Appl Pharmacol 151(1):166-173. PMID:9705900
  • Caron RM. 1998. Developmentally specific effects of the DNA crosslinking agent mitomycin C on phosphoenolpyruvate carboxykinase gene expression in vivo: Correlation with changes in chromatin structure within the promoter region of the gene. J Biochem Mol Toxicol 12:325-337. PMID:9736481
  • Hamilton JW, Kaltreider RC, Bajenova OV, Ihnat MA, McCaffrey J, Turpie BW, Rowell EE, Oh J, Nemeth MJ, Pesce CA, Lariviere JP. 1998. Molecular basis for effects of carcinogenic heavy metals on inducible gene expression. Environ Health Perspect 106Suppl.4:1005-1015. PMID:9703486
  • Warren AJ, Ihnat MA, Ogdon SE, Rowell EE, Hamilton JW. 1998. Binding of nuclear proteins associated with mammalian DNA repair to the mitomycin C-DNA interstrand crosslink. Environ Mol Mutagen 31:70-81. PMID:9464318
  • Warren AJ, Maccubbin AE, Hamilton JW. 1998. Detection of mitomycin C-DNA adducts in vivo by 32P-postlabeling: Time course for formation and removal of adducts and biochemical modulation. Cancer Res 58:453-461. PMID:9458089


  • Bajenova OV, Lariviere JP, Oh J, Ihnat MA, Hamilton JW. 1997. Effects of carcinogens on inducible gene expression using cell lines stably transfected with a PEPCK/luciferase model gene. Proc Am Assoc Cancer Res
  • Ihnat MA, Lariviere JP, Warren AJ, La Ronde N, Blaxall JN, Pierre KM, Turpie BW, Hamilton JW. 1997. Suppression of p-glycoprotein expression and multi-drug resistance by DNA crosslinking agents. Clin Cancer Res 3:1339-1346. PMID:9815817


  • Ihnat MA, Hamilton JW. 1996. Suppression of p-glycoprotein expression and multi-drug resistance by DNA cross-linking agents in rat and human cancer cells. Proc Am Assoc Cancer Res 37:333.
  • Warren AJ. 1996. Detection of mammalian nuclear proteins that specifically recognize the mitomycin C-DNA interstrand CpG crosslink. Proc Am Assoc Cancer Res 37:121-122.
  • Warren AJ, Hamilton JW. 1996. Synthesis and structural characterization of the N2G-mitomycin C-N2G interstrand crosslink in a model synthetic 23 base pair oligonucleotide DNA duplex. Chem Res Toxicol 9:1063-1071. PMID:8902260


  • Caron RM. 1995. Developmentally specific effects of mitomycin C on PEPCK gene expression and correlation with chromatin structure. Proc Am Assoc Cancer Res 36:158.
  • Caron RM. 1995. Preferential effects of the chemotherapeutic DNA crosslinking agent mitomycin C on inducible gene expression in vivo. Environ Mol Mutagen 25:4-11. PMID:7875125
  • Ihnat MA. 1995. Suppression of multi-drug resistance gene mdr1b mRNA and p-glycoprotein expression by mitomycin C in rat H4IIE cells. Proc Am Assoc Cancer Res 36:345.
  • Jacobs JM. 1995. Terminal enzymes of heme biosynthesis in the plant plasma membrane. Arch Biochem Biophys 323(2):274-8. PMID:7487088


  • McCaffrey J, Wolf CM, Hamilton JW. 1994. Effects of the genotoxic carcinogen chromium (VI) on basal and hormone-inducible phosphoenolpyruvate carboxykinase gene expression in vivo: correlation with glucocorticoid- and developmentally-regulated expression. Mol Carcinog 10:189-198. PMID:8068179
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