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Project Publications: New York University School of Medicine: Detection of Cr-DNA Adducts in Human Cells

Superfund Research Program

Detection of Cr-DNA Adducts in Human Cells

Project Leader: Max Costa
Grant Number: P42ES010344
Funding Period: 2000 - 2006

Project-Specific Links





  • Guo W, Yang Z, Xia Q, Liu J, Yu Y, Li J, Zuo Z, Zhang D, Li X, Shi X, Huang C. 2011. Arsenite stabilizes HIF-1 alpha protein through p85 alpha-mediated up-regulation of inducible Hsp70 protein expression. Cellular and Molecular Life Sciences 68(3):475-488. doi:10.1007/s00018-010-0459-7 PMID:20835880 PMCID:PMC3758129 (Completed with ARRA Funds)
  • Tchou-Wong KM, Kiok K, Tang Z, Kluz T, Smith PR, Brown S, Costa M, Arita A. 2011. Effects of nickel treatment on H3K4 trimethylation and gene expression. PLoS One 6(3):doi:10.1371/journal.pone.0017728 PMID:21455298 PMCID:PMC3063782 (Completed with ARRA Funds)


  • Chen H, Kluz T, Zhang R, Costa M. 2010. Hypoxia and nickel inhibit histone demethylase JMJD1A and repress Spry2 expression in human bronchial epithelial BEAS-2B cells. Carcinogenesis 31:2136-2144. doi:10.1093/carcin/bgq197 PMID:20881000 PMCID:PMC2994281 (Completed with ARRA Funds)


  • Li Q, Suen T, Sun H, Arita A, Costa M. 2009. Nickel compounds induce apoptosis in human bronchial epithelial Beas-2B cells by activation of c-Myc through ERK pathway. Toxicol Appl Pharmacol 235(2):191-198. doi:10.1016/j.taap.2008.12.005 PMID:19135467 PMCID:PMC2657554 (Completed with ARRA Funds)



  • Uddin AN, Burns FJ, Rossman TG, Chen H, Kluz T, Costa M. 2007. Dietary chromium and nickel enhance UV-carcinogenesis in skin of hairless mice. Toxicol Appl Pharmacol 221(3):329-38. PMID:17499830


  • Arakawa H, Wu F, Costa M. 2006. Sequence specificity of Cr(III)-DNA adduct formation in the p53 gene: NGG sequences are preferential adduct-forming sites. Carcinogenesis 27(3):639-645. PMID:16251206
  • Chen H, Ke Q, Kluz T, Yan Y, Costa M. 2006. Nickel ions increase histone H3 lysine 9 dimethylation and induce transgene silencing. Mol Cell Biol 26(10):3728-3737. PMID:16648469
  • Costa M, Klein C. 2006. Toxicity and carcinogenicity of chromium compounds in humans. Crit Rev Toxicol 36(2):155-163. PMID:16736941
  • Garrick MD, Singleton S, Vargas F, Kuo H, Zhao L, Knopfel M, Davidson T, Costa M, Paradkar P, Roth JA, Garrick LM. 2006. DMT1: which metals does it transport?. Biol Res 39(1):79-85. PMID:16629167
  • Kang GS, Li Q, Chen H, Costa M. 2006. Effect of metal ions on HIF-1alpha and Fe homeostasis in human A549 cells. Mutat Res 610(1-2):48-55. doi:10.1016/j.mrgentox.2006.06.012 PMID:16877034
  • Ke Q, Davidson T, Chen H, Kluz T, Costa M. 2006. Alterations of histone modifications and transgene silencing by nickel chloride. Carcinogenesis 27(7):1481-1488. PMID:16522665
  • Li Q, Chen H, Huang X, Costa M. 2006. Effects of 12 metal ions on iron regulatory protein 1 (IRP-1) and hypoxia-inducible factor-1 alpha (HIF-1alpha) and HIF-regulated genes. Toxicol Appl Pharmacol 213(3):245-255. doi:10.1016/j.taap.2005.11.006 PMID:16386771 PMCID:PMC2965073


  • Chen H, Davidson T, Singleton S, Garrick MD, Costa M. 2005. Nickel decreases cellular iron level and converts cytosolic aconitase to iron-regulatory protein 1 in A549 cells. Toxicol Appl Pharmacol 206(3):275-287. PMID:16039939
  • Davidson T, Chen H, Garrick MD, D'Angelo G, Costa M. 2005. Soluble nickel interferes with cellular iron homeostasis. Mol Cell Biochem 279(1-2):157-162. PMID:16283525


  • Caruso RP, Levinson B, Melamed J, Wieczorek R, Taneja S, Polsky D, Chang C, Zeleniuch-Jacquotte A, Salnikow K, Yee H, Costa M, Osman I. 2004. Altered N-myc downstream-regulated gene 1 protein expression in African-American compared with caucasian prostate cancer patients. Clin Cancer Res 10(1):222-227. PMID:14734473
  • Davidson T, Kluz T, Burns FJ, Rossman TG, Zhang Q, Uddin AN, Nadas A, Costa M. 2004. Exposure to chromium(VI) in the drinking water increases susceptibility to UV-induced skin tumors in hairless mice. Toxicol Appl Pharmacol 196(3):431-437. PMID:15094314
  • Li J, Davidson G, Huang Y, Jiang B, Shi X, Costa M, Huang C. 2004. Nickel compounds act through phosphatidylinositol-3-kinase/Akt-dependent, p70(S6k)-independent pathway to induce hypoxia inducible factor transactivation and Cap43 expression in mouse epidermal Cl41 cells. Cancer Res 64(1):94-101. PMID:14729612
  • Li J, Dokka S, Wang L, Shi X, Castranova V, Yan Y, Costa M, Huang C. 2004. Activation of aPKC is required for vanadate-induced phosphorylation of protein kinase B (Akt), but not p70S6k in mouse epidermal JB6 cells. Mol Cell Biochem 255(1-2):217-225. PMID:14971662
  • Zhao J, Chen H, Davidson T, Kluz T, Zhang Q, Costa M. 2004. Nickel-induced 1,4-alpha-glucan branching enzyme 1 up-regulation via the hypoxic signaling pathway. Toxicol Appl Pharmacol 196(3):404-409. PMID:15094311
  • Zhao J, Yan Y, Salnikow K, Kluz T, Costa M. 2004. Nickel-induced down-regulation of serpin by hypoxic signaling. Toxicol Appl Pharmacol 194(1):60-68. PMID:14728980


  • Costa M. 2003. Potential hazards of hexavalent Cr in our drinking water. Toxicol Appl Pharmacol 188(1):1-5. PMID:12668116
  • Costa M, Yan Y, Zhou D, Salnikow K. 2003. Molecular mechanisms of nickel carcinogenesis: gene silencing by nickel delivery to the nucleus and gene activation/inactivation by nickel-induced cell signaling. J Environ Monit 5(2):222-223. PMID:12729258
  • Davidson T, Salnikow K, Costa M. 2003. Hypoxia inducible factor-1 alpha-independent suppression of aryl hydrocarbon receptor-regulated genes by nickel. Mol Pharmacol 64(6):1485-1493. PMID:14645679
  • Feng Z, Hu W, Rom WN, Costa M, Tang M. 2003. Chromium(VI) exposure enhances polycyclic aromatic hydrocarbon-DNA binding at the p53 gene in human lung cells. Carcinogenesis 24(4):771-778. PMID:12727806
  • Salnikow K, Davidson T, Kluz T, Chen H, Zhou D, Costa M. 2003. GeneChip analysis of signaling pathways effected by nickel. J Environ Monit 5(2):206-209. PMID:12729255
  • Salnikow K, Davidson T, Zhang Q, Chen L, Su W, Costa M. 2003. The involvement of hypoxia-inducible transcription factor-1-dependent pathway in nickel carcinogenesis. Cancer Res 63(13):3524-3530. PMID:12839937
  • Yan Y, Kluz T, Zhang P, Chen H, Costa M. 2003. Analysis of specific lysine histone H3 and H4 acetylation and methylation status in clones of cells with a gene silenced by nickel exposure. Toxicol Appl Pharmacol 190(3):272-277. PMID:12902198
  • Zhang Q, Salnikow K, Kluz T, Chen L, Su W, Costa M. 2003. Inhibition and reversal of nickel-induced transformation by the histone deacetylase inhibitor trichostatin A. Toxicol Appl Pharmacol 192(3):201-211. PMID:14575637


  • Cangul H, Broday L, Salnikow K, Sutherland JE, Peng W, Zhang Q, Poltaratsky V, Yee H, Zoroddu MA, Costa M. 2002. Molecular mechanisms of nickel carcinogenesis. Toxicol Lett 127(1-3):69-75. PMID:12052643
  • Cangul H, Salnikow K, Yee H, Zagzag D, Commes T, Costa M. 2002. Enhanced expression of a novel protein in human cancer cells: a potential aid to cancer diagnosis. Cell Biol Toxicol 18(2):87-96. PMID:12046693
  • Cangul H, Salnikow K, Yee H, Zagzag D, Commes T, Costa M. 2002. Enhanced overexpression of an HIF-1/hypoxia-related protein in cancer cells. Environ Health Perspect 110(Suppl.5):783-788. PMID:12429530
  • Costa M. 2002. Molecular mechanisms of nickel carcinogenesis. Biol Chem 383(6):961-967. doi:10.1515/BC.2002.102 PMID:12222685
  • Costa M, Salnikow K, Sutherland JE, Broday L, Peng W, Zhang Q, Kluz T. 2002. The role of oxidative stress in nickel and chromate genotoxicity. Mol Cell Biochem 234-235(1-2):265-275. PMID:12162442
  • Salnikow K, Davidson T, Costa M. 2002. The role of hypoxia-inducible signaling pathway in nickel carcinogenesis. Environ Health Perspect 110(Suppl.5):831-834. PMID:12426141
  • Salnikow K, Kluz T, Costa M, Piquemal D, Demidenko ZN, Xie K, Blagosklonny MV. 2002. The regulation of hypoxic genes by calcium involves c-Jun/AP-1, which cooperates with hypoxia-inducible factor 1 in response to hypoxia. Mol Cell Biol 22(6):1734-1741. PMID:11865053 PMCID:PMC135615
  • Zhang Q, Kluz T, Salnikow K, Costa M. 2002. Comparison of the cytotoxicity, cellular uptake, and DNA-protein crosslinks induced by potassium chromate in lymphoblast cell lines derived from three different individuals. Biol Trace Elem Res 86(1):11-22. PMID:12002656
  • Zoroddu MA, Peana M, Kowalik-Jankowska T, Kozlowski H, Costa M. 2002. The binding of Ni(II) and Cu(II) with the N-terminal tail of the histone H4. Journal of the Chemical Society - Dalton Transactions 3:458-465.


  • Costa M, Sutherland JE, Peng W, Salnikow K, Broday L, Kluz T. 2001. Molecular biology of nickel carcinogenesis. Mol Cell Biochem 222(1-2):205-211. PMID:11678603
  • Huang C, Li J, Costa M, Zhang Z, Leonard SS, Castranova V, Vallyathan V, Ju G, Shi X. 2001. Hydrogen peroxide mediates activation of nuclear factor of activated T cells (NFAT) by nickel subsulfide. Cancer Res 61:8051-8057. PMID:11719426
  • Huang C, Li J, Ding M, Costa M, Castranova V, Vallyathan V, Ju G, Shi X. 2001. Transactivation of RARE and GRE in the cellular response to arsenic. Mol Cell Biochem 222:119-125. PMID:11678593
  • Huang C, Li J, Ding M, Wang L, Shi X, Castranova V, Vallyathan V, Ju G, Costa M. 2001. Arsenic-induced NF kappa beta transactivation through Erks- and JNKs-dependent pathways in mouse epidermal JB6 cells. Mol Cell Biochem 222:29-34. PMID:11678607
  • Huang C, Zhang Q, Li J, Shi X, Castranova V, Ju G, Costa M, Dong Z. 2001. Involvement of Erks activation in cadmium-induced AP-1 transactivation in vitro and in vivo. Mol Cell Biochem 222(1-2):141-147. doi:10.1023/A:1017953927347 PMID:11678596
  • Sutherland JE, Peng W, Zhang Q, Costa M. 2001. The histone deacetylase inhibitor trichostatin A reduces nickel-induced gene silencing in yeast and mammalian cells. Mutat Res 479(1-2):225-233. PMID:11470494
  • Zoroddu MA, Kowalik-Jankowska T, Kozlowski H, Salnikow K, Costa M. 2001. Ni(II) and Cu(II) binding with a 14-aminoacid sequence of Cap43 protein, TRSRSHTSEGTRSR. J Inorg Biochem 84:47-54. PMID:11330481


  • Cohen M, Costa M. 2000. Chromium. In: Environmental Toxicants, Human Exposures and their Health Effects (2nd Edition). John Wiley & Sons, Inc, New York, NY. pp.173-192.
  • Costa M. 2000. Chromium. In: Molecular Biology and Toxicology of Metals. Taylor & Francis, Inc., New York, NY. pp.113-128.
  • Sutherland JE, Zhitkovich A, Kluz T, Costa M. 2000. Rats retain chromium in tissues following chronic ingestion of drinking water containing hexavalent chromium. Biol Trace Elem Res 74(1):41-53. PMID:11049199
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