Transition mutation in codon 248 of the p53 tumor suppressor gene induced by reactive oxygen species and a nitric oxide-releasing compound

Carcinogenesis. 2000 Feb;21(2):281-7. doi: 10.1093/carcin/21.2.281.


Exposing the human bronchial epithelial cell line BEAS-2B to the nitric oxide (NO) donor sodium 1-(N,N-diethylamino)diazen-1-ium-1, 2-diolate (DEA/NO) at an initial concentration of 0.6 mM while generating superoxide ion at the rate of 1 microM/min with the hypoxanthine/xanthine oxidase (HX/XO) system induced C:G-->T:A transition mutations in codon 248 of the p53 gene. This pattern of mutagenicity was not seen by 'fish-restriction fragment length polymorphism/polymerase chain reaction' (fish-RFLP/PCR) on exposure to DEA/NO alone, however, exposure to HX/XO led to various mutations, suggesting that co-generation of NO and superoxide was responsible for inducing the observed point mutation. DEA/NO potentiated the ability of HX/XO to induce lipid peroxidation as well as DNA single- and double-strand breaks under these conditions, while 0.6 mM DEA/NO in the absence of HX/XO had no significant effect on these parameters. The results show that a point mutation seen at high frequency in certain common human tumors can be induced by simultaneous exposure to reactive oxygen species and a NO source.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Polyomavirus Transforming / physiology
  • Bronchi / cytology
  • Cell Line, Transformed
  • Codon / chemistry
  • Codon / genetics*
  • DNA Damage*
  • DNA Fragmentation
  • Drug Synergism
  • Epithelial Cells / chemistry
  • Epithelial Cells / cytology
  • Genes, p53 / drug effects*
  • Genes, p53 / genetics
  • Humans
  • Hydrazines / pharmacology
  • Hydrazines / toxicity*
  • Hypoxanthine / metabolism
  • Lipid Peroxidation
  • Nitric Oxide / metabolism
  • Nitric Oxide Donors / pharmacology
  • Nitric Oxide Donors / toxicity*
  • Nitrogen Oxides
  • Point Mutation*
  • Reactive Oxygen Species*
  • Superoxides / metabolism
  • Xanthine Oxidase / metabolism


  • Antigens, Polyomavirus Transforming
  • Codon
  • Hydrazines
  • Nitric Oxide Donors
  • Nitrogen Oxides
  • Reactive Oxygen Species
  • Superoxides
  • Hypoxanthine
  • Nitric Oxide
  • 1,1-diethyl-2-hydroxy-2-nitrosohydrazine
  • Xanthine Oxidase