The inhibitory effect of vitamin E on K-ras mutation at an early stage of lung carcinogenesis in mice

Eur J Pharmacol. 1997 Mar 26;323(1):99-102. doi: 10.1016/s0014-2999(97)00094-0.


In this study, we investigated the effect of vitamin E on the activation of the K-ras oncogene with a 61st codon A-->T mutation at an early stage of urethane-induced lung carcinogenesis in mice. Thirty days after urethane injection, the K-ras mutation was detected in 64% of lung samples tested by mutant-allele-specific amplification. The consumption of a supplemented diet with about 20-times more vitamin E than the control diet, only during the promotion phase or during both the initiation and promotion phases of lung carcinogenesis, reduced the frequency of the mutation to 36 and 18%, respectively. Also, vitamin E suppressed the level of proliferating cell nuclear antigen as a marker of cell proliferation in the lungs of mice treated with urethane. These results support the notion that vitamin E is a useful chemopreventive agent against lung cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Southern
  • Cell Division / drug effects
  • Disease Models, Animal
  • Genes, ras / drug effects*
  • Genes, ras / genetics
  • Lung / drug effects
  • Lung / metabolism
  • Lung Neoplasms / chemically induced
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics*
  • Male
  • Mice
  • Point Mutation / drug effects*
  • Point Mutation / genetics
  • Polymerase Chain Reaction
  • Specific Pathogen-Free Organisms
  • Urethane / administration & dosage
  • Urethane / toxicity
  • Vitamin E / administration & dosage
  • Vitamin E / pharmacology*
  • Vitamin E / therapeutic use


  • Vitamin E
  • Urethane