Differential gene expression in nickel(II)-treated normal rat kidney cells

Res Commun Mol Pathol Pharmacol. 2006;119(1-6):77-87.

Abstract

Nickel(II) compounds are carcinogenic metals which induce genotoxicity and oxidative stress through the generation of reactive oxygen species. In search of new molecular pathways toward understanding the molecular mechanism of nickel(II)-induced carcinogensis, we performed mRNA differential display analysis using total RNA extracted from nickel(II) acetate-treated normal rat kidney cells (NRK-52E). Cells were exposed for 2 months to 160 and 240 microM nickel(II) concentrations. cDNAs corresponding to mRNAs for which expression levels were altered by nickel(II) were isolated, sequenced, and followed by a GenBank Blast homology search. Specificity of differential expression of cDNAs was determined by RT-PCR. Two of them (SH3BGRL3 and FHIT) were down-regulated and one (metallothionein) was up-regulated by nickel(II) treatment. The expression of these mRNAs were nickel(II) concentration-dependent. Overall, although the fundamental questions related to function of these genes in nickel(II)-mediated carcinogenicity are not answered, our study suggests that they can be interesting candidates for studies of molecular mechanisms of nickel(II) carcinogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetates / toxicity*
  • Acid Anhydride Hydrolases / genetics
  • Acid Anhydride Hydrolases / metabolism*
  • Animals
  • Cell Line
  • DNA, Complementary / genetics
  • DNA, Complementary / isolation & purification
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation / drug effects*
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Kidney / cytology
  • Metallothionein / genetics
  • Metallothionein / metabolism*
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Organometallic Compounds / toxicity*
  • RNA, Messenger / metabolism
  • Rats
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Analysis, DNA
  • Time Factors

Substances

  • Acetates
  • DNA, Complementary
  • Intracellular Signaling Peptides and Proteins
  • Neoplasm Proteins
  • Organometallic Compounds
  • RNA, Messenger
  • fragile histidine triad protein
  • Metallothionein
  • nickel acetate
  • Acid Anhydride Hydrolases