Research Article

Oncogene expression profiles in K6/ODC mouse skin and papillomas following a chronic exposure to monomethylarsonous acid†

  1. Don A. Delker1,*,
  2. David R. Geter1,
  3. Barbara C. Roop1,
  4. William O. Ward1,
  5. Gene J. Ahlborn1,
  6. James W. Allen1,
  7. Gail M. Nelson1,
  8. Ming Ouyang2,
  9. William Welsh2,
  10. Yan Chen3,
  11. Thomas O'Brien3,
  12. Kirk T. Kitchin1

Article first published online: 18 DEC 2009

DOI: 10.1002/jbt.20304

Issue

Journal of Biochemical and Molecular Toxicology

Journal of Biochemical and Molecular Toxicology

Volume 23, Issue 6, pages 406–418, November/December 2009

Additional Information

How to Cite

Delker, D. A., Geter, D. R., Roop, B. C., Ward, W. O., Ahlborn, G. J., Allen, J. W., Nelson, G. M., Ouyang, M., Welsh, W., Chen, Y., O'Brien, T. and Kitchin, K. T. (2009), Oncogene expression profiles in K6/ODC mouse skin and papillomas following a chronic exposure to monomethylarsonous acid. Journal of Biochemical and Molecular Toxicology, 23: 406–418. doi: 10.1002/jbt.20304

Author Information

  1. 1

    National Health and Environmental Effects Research Laboratory, Office of Research and Development Environmental Carcinogenesis Division, United States Environmental Protection Agency, Research Triangle Park, NC 27711, USA

  2. 2

    Robert Wood Johnson Medical School & The Informatics Institute of UMDNJ, University of Medicine and Dentistry of New Jersey (UMDNJ), Piscataway, NJ 08854, USA

  3. 3

    ODC Mouse Group, Inc., Drexel Hill, PA 19026, USA

*School of Medicine, University of Utah, Salt Lake City, UT 84132, USA

  1. †

    The research described in this article has been reviewed by the National Health and Environmental Effects Research Laboratory, United States Environmental Protection Agency, and approved for publication. Approval does not signify that the contents necessarily reflect the views of the Agency, nor does the mention of trade names or commercial products constitute endorsement or recommendation for use.

Publication History

  1. Issue published online: 7 JAN 2010
  2. Article first published online: 18 DEC 2009
  3. Manuscript Accepted: 9 MAY 2009
  4. Manuscript Revised: 3 MAR 2009
  5. Manuscript Received: 19 JAN 2009

SEARCH

SEARCH BY CITATION

ARTICLE TOOLS

Get PDF (326K)

Keywords:

  • Gene Expression;
  • Monomethylarsonous Acid;
  • Skin;
  • K6/ODC Mouse;
  • Squamous Papillomas;
  • Arsenic

Abstract

We have previously observed that a chronic drinking water exposure to monomethylarsonous acid [MMA(III)], a cellular metabolite of inorganic arsenic, increases tumor frequency in the skin of keratin VI/ornithine decarboxylase (K6/ODC) transgenic mice. To characterize gene expression profiles predictive of MMA(III) exposure and mode of action of carcinogenesis, skin and papilloma RNA was isolated from K6/ODC mice administered 0, 10, 50, and 100 ppm MMA(III) in their drinking water for 26 weeks. Following RNA processing, the resulting cRNA samples were hybridized to Affymetrix Mouse Genome 430A 2.0 GeneChips®. Micoarray data were normalized using MAS 5.0 software, and statistically significant genes were determined using a regularized t-test. Significant changes in bZIP transcription factors, MAP kinase signaling, chromatin remodeling, and lipid metabolism gene transcripts were observed following MMA(III) exposure as determined using the Database for Annotation, Visualization and Integrated Discovery 2.1 (DAVID) (Dennis et al., Genome Biol 2003;4(5):P3). MMA(III) also caused dose-dependent changes in multiple Rho guanine nucleotide triphosphatase (GTPase) and cell cycle related genes as determined by linear regression analyses. Observed increases in transcript abundance of Fosl1, Myc, and Rac1 oncogenes in mouse skin support previous reports on the inducibility of these oncogenes in response to arsenic and support the relevance of these genomic changes in skin tumor induction in the K6/ODC mouse model. © 2009 Wiley Periodicals, Inc. J Biochem Mol Toxicol 23:406–418, 2009; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20304

Get PDF (326K)