Proteomic and biochemical analyses of in vitro carcinogen-induced lung cell transformation: synergism between arsenic and benzo[a]pyrene

Proteomics. 2006 Mar;6(5):1619-30. doi: 10.1002/pmic.200500332.


Chronic coexposures to carcinogens inorganic arsenic and benzo[a]pyrene (B[a]P) are common in the living environment. However, little is known about their effects exerted at the proteome level. Our previous study in rat lung epithelial cells showed that cell transformation frequency increased by more than 100-fold when arsenic was given in combination with B[a]P than cells either exposed to arsenic or B[a]P alone. This demonstrated a synergism between them. Here, we reported that alterations to the proteome varied and were more pronounced in the transformed cells that were exposed to a combination of arsenic and B[a]P than to B[a]P and much less to arsenic alone when compared to passage-matched control cells. In general, three proteins belonging to intermediate filaments were found to be significantly down-regulated and six proteins belonging to antioxidative stress-, chaperone-, and glycolytic proteins were up-regulated in these transformed cells. These transformed cells were also associated with an increase of proliferation and de-differentiation. Taken together, our findings suggest that although arsenic or B[a]P alone is sufficient to induce cell transformation and alter the proteome to a similar extent, the effects of coexposure are much more pronounced. This further substantiates the notion that these carcinogens act in concert during cocarcinogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actinin / metabolism
  • Actins / metabolism
  • Animals
  • Arsenic* / metabolism
  • Arsenic* / pharmacology
  • Benzo(a)pyrene* / metabolism
  • Benzo(a)pyrene* / pharmacology
  • Carcinogens* / metabolism
  • Carcinogens* / pharmacology
  • Cell Line
  • Cell Transformation, Neoplastic*
  • Electrophoresis, Gel, Two-Dimensional
  • Extracellular Signal-Regulated MAP Kinases / chemistry
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Intermediate Filament Proteins / chemistry
  • Intermediate Filament Proteins / metabolism
  • Lung / cytology
  • Lung / drug effects*
  • Lung / metabolism
  • Lung / pathology*
  • MAP Kinase Signaling System / physiology
  • Membrane Glycoproteins / chemistry
  • Membrane Glycoproteins / metabolism
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / metabolism
  • Peptides / genetics
  • Peptides / metabolism
  • Peripherins
  • Proteome / analysis*
  • Rats
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization


  • Actins
  • Carcinogens
  • Intermediate Filament Proteins
  • Membrane Glycoproteins
  • Nerve Tissue Proteins
  • Peptides
  • Peripherins
  • Proteome
  • smooth muscle actin, rat
  • Actinin
  • Benzo(a)pyrene
  • Extracellular Signal-Regulated MAP Kinases
  • Arsenic