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Molecular and Cellular Biochemistry

, Volume 279, Issue 1–2, pp 169–181 | Cite as

Resistance to apoptosis, increased growth potential, and altered gene expression in cells that survived genotoxic hexavalent chromium [Cr(VI)] exposure

  • Daryl E. Pritchard
  • Susan Ceryak
  • Keri E. Ramsey
  • Travis J. O'Brien
  • Linan Ha
  • Jamie L. Fornsaglio
  • Dietrich A. Stephan
  • Steven R. PatiernoEmail author
Article

Abstract

Certain hexavalent chromium [Cr(VI)] compounds are known genotoxic respiratory carcinogens, which induce apoptosis as a predominant mode of cell death. Selection of cells that are resistant to apoptosis may be a factor in tumour progression. We developed sub-populations of telomerase-transfected human fibroblasts (BJ-hTERT) that survived a 99% clonogenically lethal exposure to Cr(VI) (B-5Cr). B-5Cr cells were markedly resistant to apoptosis induced by several agents and exhibited increased clonogenic survival, especially at apoptogenic doses. B-5Cr cells did not exhibit altered cellular uptake of Cr(VI) and retained a normal p53 response to Cr(VI) exposure. We conducted large-scale gene expression analysis at different time-points after a secondary genotoxic Cr(VI) insult in B-5Cr and BJ-hTERT cells using Affymetrix Genechip® human genome arrays. Cr(VI) exposure led to differential regulation of many genes, which affect a diverse set of cellular activities such as transcription, signal transduction, stress response, cell adhesion, DNA repair, apoptosis and cell cycle modulation. We compared Cr(VI)-induced altered gene expression in the B-5Cr cells to that in the parental cells and identified 223, 147 and 204 genes with at least a two-fold difference in expression at 4, 8 and 18 h after exposure, respectively. Cluster analysis by gene function revealed altered expression of genes involved in apoptosis, cell cycle regulation and DNA repair. Our data suggest an alteration in gene expression that may favor cell survival and/or incomplete DNA repair after genotoxic exposure. Selection of cells with altered expression of these genes may constitute the early stages of tumour progression.

Keywords

Hexavalent Chromium Altered Gene Expression Genome Array Clonogenic Survival Cell Cycle Modulation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science + Business Media, Inc. 2005

Authors and Affiliations

  • Daryl E. Pritchard
    • 1
  • Susan Ceryak
    • 1
  • Keri E. Ramsey
    • 2
  • Travis J. O'Brien
    • 1
  • Linan Ha
    • 1
  • Jamie L. Fornsaglio
    • 1
  • Dietrich A. Stephan
    • 2
  • Steven R. Patierno
    • 1
    • 3
    Email author
  1. 1.The George Washington University Medical CenterWashingtonUSA
  2. 2.Translational Genomics Research InstitutePhoenixUSA
  3. 3.Department of PharmacologyThe George Washington University Medical CenterWashingtonUSA

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