Effects of tobacco-specific nitrosamines and snuff extract on cell proliferation and activities of ornithine decarboxylase and aryl hydrocarbon hydroxylase in mouse tongue primary epithelial cell cultures

J Cancer Res Clin Oncol. 1989;115(6):558-63. doi: 10.1007/BF00391358.


Tobacco and its related compounds, including snuff, have been implicated in oral cancers. Tobacco-specific nitrosamines have been shown to be the causative agents present in tobacco and its related compounds. Both, N-nitrosonornicotine (NNN) and its butanone derivative (NNK) are carcinogenic in animals. In our in vitro studies using embryonic mouse tongue epithelial cells, NNN is linked to an increase in [3H]dT uptake along with a concomitant increase in ornithine decarboxylase and aryl hydrocarbon hydroxylase activities. NNK, the more potent compared to NNN, causes a further increase in [3H]dT uptake, cell count and ornithine decarboxylase activity. However, aryl hydrocarbon hydroxylase behaves differently in cultures treated with NNK compared to those treated with NNN. Snuff extract has an overall inhibitory effect on cell count, [3H]dT uptake, and ornithine decarboxylase and aryl hydrocarbon hydroxylase activities when administered either alone or in combination with NNN and NNK. How the inhibitory effect of snuff in the presence of tobacco-specific nitrosamines is involved in oral carcinogenesis should be further investigated.

MeSH terms

  • Animals
  • Aryl Hydrocarbon Hydroxylases / metabolism
  • Carcinogens*
  • Cell Division / drug effects
  • Cells, Cultured
  • Epithelium / drug effects
  • Epithelium / enzymology
  • Epithelium / pathology
  • Mice
  • Mice, Inbred BALB C
  • Mouth Neoplasms / chemically induced
  • Nitrosamines / toxicity*
  • Ornithine Decarboxylase / metabolism*
  • Plants, Toxic*
  • Tobacco / analysis*
  • Tobacco, Smokeless / analysis*
  • Tongue / drug effects
  • Tongue / enzymology*
  • Tongue / pathology


  • Carcinogens
  • Nitrosamines
  • 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone
  • Aryl Hydrocarbon Hydroxylases
  • Ornithine Decarboxylase
  • N'-nitrosonornicotine