Possible role of lipid peroxidation in the induction of NF-kappa B and AP-1 in RFL-6 cells by crocidolite asbestos: evidence following protection by vitamin E

Environ Health Perspect. 1997 Sep;105 Suppl 5(Suppl 5):1127-30. doi: 10.1289/ehp.97105s51127.


Asbestos fibers cause persistent induction of the oxidative stress sensitive transcription factors nuclear factor kappa-B (NF-kappa B) and activator protein-1 (AP-1) in mammalian cells. These transcription factors play an important role in the regulation of cellular activity. Lipid peroxidation, mediated by reactive oxygen species, is thought to be a possible mechanism in the pathogenicity of asbestos fibers. These studies were designed to determine if crocidolite asbestos-induced lipid peroxidation plays a role in the mechanism of formation of NF-kappa B and AP-1. Treatment of a rat lung fibroblast cell line (RFL-6) with crocidolite asbestos in the presence and absence of the membrane antioxidant vitamin E decreased the levels of crocidolite-induced AP-1 and NF-kappa B to background levels. Preincubation of RFL-6 cells with 5,8,11,14-eicosatetraynoic acid, an inhibitor of arachidonic acid metabolism, prior to exposure to crocidolite, abrogated crocidolite-induced NF-kappa B DNA-binding activity to background levels. Coincubation with indomethacin, a cyclooxygenase inhibitor, had no effect on NF-kappa B DNA-binding activity induced by crocidolite. However, nordihydroguaiaretic acid, a lipoxygenase inhibitor, decreased levels of NF-kappa B to background levels. This would suggest that lipoxygenase metabolites of arachidonic acid, produced following lipid peroxidation, are involved in the cellular signalling events to NF-kappa B transcription factor induction by asbestos.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arachidonic Acid / metabolism
  • Asbestos, Crocidolite / toxicity*
  • Carcinogens / antagonists & inhibitors*
  • Carcinogens / toxicity*
  • Cell Line
  • Cells, Cultured
  • Cyclooxygenase Inhibitors / pharmacology
  • DNA / biosynthesis
  • Lipid Peroxidation / drug effects
  • Lipid Peroxidation / physiology*
  • Lipoxygenase Inhibitors / pharmacology
  • NF-kappa B / biosynthesis*
  • Rats
  • Transcription Factor AP-1 / biosynthesis*
  • Vitamin E / pharmacology*


  • Carcinogens
  • Cyclooxygenase Inhibitors
  • Lipoxygenase Inhibitors
  • NF-kappa B
  • Transcription Factor AP-1
  • Asbestos, Crocidolite
  • Vitamin E
  • Arachidonic Acid
  • DNA