Participation of nitric oxide and iron in the oxidation of DNA in asbestos-treated human lung epithelial cells

Arch Biochem Biophys. 1996 Feb 1;326(1):152-7. doi: 10.1006/abbi.1996.0059.


Treatment of human lung epithelial (A549) cells with crocidolite resulted in the formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in the DNA, synthesis of mRNA for the inducible form of nitric oxide synthase (NOS), and increased intracellular nitrite (NO2-), a stable oxidation product of NO. Iron, associated with crocidolite, was involved in both NO2- and 8-OHdG formation. Addition of the NOS inhibitor, aminoguanidine (AG), reduced intracellular NO2- and prevented formation of 8-OHdG in crocidolite-treated cells, suggesting that NO was required in 8-OHdG formation. Addition of an NO-generating compound, diethyltriamine/NO, with AG and crocidolite resulted in recovery of 8-OHdG, further supporting a role for NO in oxidation of deoxyguanosine.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Asbestos / toxicity*
  • Base Sequence
  • Carcinogens / toxicity*
  • Cell Line
  • DNA / metabolism*
  • Epithelium / metabolism
  • Humans
  • Iron / metabolism*
  • Lung / metabolism*
  • Molecular Sequence Data
  • Nitric Oxide / metabolism*
  • Oxidation-Reduction


  • Carcinogens
  • Asbestos
  • Nitric Oxide
  • DNA
  • Iron