Effects of nickel, chromate, and arsenite on histone 3 lysine methylation

Toxicol Appl Pharmacol. 2009 Apr 1;236(1):78-84. doi: 10.1016/j.taap.2009.01.009. Epub 2009 Jan 27.


Occupational exposure to nickel (Ni), chromium (Cr), and arsenic (As) containing compounds has been associated with lung cancer and other adverse health effects. Their carcinogenic properties may be attributable in part, to activation and/or repression of gene expression induced by changes in the DNA methylation status and histone tail post-translational modifications. Here we show that individual treatment with nickel, chromate, and arsenite all affect the gene activating mark H3K4 methylation. We found that nickel (1 mM), chromate (10 microM), and arsenite (1 microM) significantly increase tri-methyl H3K4 after 24 h exposure in human lung carcinoma A549 cells. Seven days of exposure to lower levels of nickel (50 and 100 microM), chromate (0.5 and 1 microM) or arsenite (0.1, 0.5 and 1 microM) also increased tri-methylated H3K4 in A549 cells. This mark still remained elevated and inherited through cell division 7 days following removal of 1 microM arsenite. We also demonstrate by dual staining immunofluorescence microscopy that both H3K4 tri-methyl and H3K9 di-methyl marks increase globally after 24 h exposure to each metal treatment in A549 cells. However, the tri-methyl H3K4 and di-methyl H3K9 marks localize in different regions in the nucleus of the cell. Thus, our study provides further evidence that a mechanism(s) of carcinogenicity of nickel, chromate, and arsenite metal compounds may involve alterations of various histone tail modifications that may in turn affect the expression of genes that may cause transformation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Arsenites / toxicity*
  • Cell Line, Tumor
  • Cell Transformation, Neoplastic / drug effects
  • Chromates / toxicity*
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation, Neoplastic / drug effects
  • Histones / metabolism*
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism*
  • Lysine
  • Methylation
  • Nickel / toxicity*
  • Potassium Compounds / toxicity*
  • Protein Processing, Post-Translational / drug effects*
  • Sodium Compounds / toxicity*
  • Time Factors


  • Arsenites
  • Chromates
  • Histones
  • Potassium Compounds
  • Sodium Compounds
  • sodium arsenite
  • nickel sulfate
  • potassium chromate(VI)
  • nickel chloride
  • Nickel
  • Lysine