Genomic instability in non-neoplastic oral mucosa cells can predict risk during 4-nitroquinoline 1-oxide-induced rat tongue carcinogenesis

Oral Oncol. 2004 Oct;40(9):910-5. doi: 10.1016/j.oraloncology.2004.04.010.


4-Nitroquinoline 1-oxide (4NQO)-induced rat tongue carcinogenesis is a useful model for studying oral squamous cell carcinoma. The aim of this study was to investigate the level of DNA damage induced by 4NQO in oral mucosa cells by the single cell gel (comet) assay. Male Wistar rats were distributed into three groups of 10 animals each and treated with 50 ppm 4NQO solution by drinking water for 4, 12 or 20 weeks. Ten animals were used as negative control. Statistically significant increase of DNA damage was observed in non-neoplastic oral cells at four weeks of 4NQO administration when compared with control (P < 0.05). The level of DNA damage was directly associated with the severity of histological changes. The results suggest that histologically normal tissue is able to harbor genetically unstable cells contributing to the initiation of oral carcinogenesis. Genomic instability appears to be associated with the risk and progression of oral cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Nitroquinoline-1-oxide
  • Animals
  • Carcinoma, Squamous Cell / chemically induced
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology
  • Cell Transformation, Neoplastic / genetics*
  • Cell Transformation, Neoplastic / pathology
  • Comet Assay / methods
  • DNA Damage
  • DNA, Neoplasm / genetics
  • Disease Progression
  • Genomic Instability*
  • Male
  • Mouth Mucosa / drug effects*
  • Mouth Mucosa / pathology
  • Precancerous Conditions / genetics
  • Precancerous Conditions / pathology
  • Rats
  • Rats, Wistar
  • Tongue Neoplasms / chemically induced
  • Tongue Neoplasms / genetics*
  • Tongue Neoplasms / pathology


  • DNA, Neoplasm
  • 4-Nitroquinoline-1-oxide