Oxidative DNA damage is a preliminary step during rat tongue carcinogenesis induced by 4-nitroquinoline 1-oxide

Sandra Regina Miranda1, Juliana Noguti, Juliana Gonçalves Carvalho

  • 1Departamento de Patologia, Universidade Federal de Sao Paulo, UNIFESP, Santos, SP, Brazil.

Insights

Oxidative DNA damage occurs early in 4-nitroquinoline 1-oxide (4NQO)-induced rat tongue cancer. This damage is detectable even in normal oral epithelium before tumors form, highlighting its role in oral carcinogenesis.

Area of Science:

  • Biochemistry
  • Toxicology
  • Oncology

Background:

  • Oral cancer is a significant global health concern.
  • Multistep carcinogenesis involves accumulating genetic and epigenetic alterations.
  • Oxidative stress is implicated in cancer development.

Purpose of the Study:

  • To investigate oxidative DNA damage during 4-nitroquinoline 1-oxide (4NQO)-induced rat tongue carcinogenesis.
  • To determine if oxidative DNA damage is an early event in oral carcinogenesis.
  • To assess the utility of specific DNA damage markers in oral cancer research.

Main Methods:

  • Male Wistar rats were exposed to 50 ppm 4NQO in drinking water for 4, 12, and 20 weeks.
  • A negative control group received no 4NQO.
  • The alkaline Comet assay with lesion-specific enzymes was employed to detect DNA strand breaks and oxidized bases.

Main Results:

  • Oxidative DNA damage was detected in normal oral epithelium after 4 weeks of 4NQO exposure, prior to histopathological abnormalities.
  • Increased oxidative DNA damage was observed in pre-neoplastic lesions (12 weeks) and squamous cell carcinomas (20 weeks) compared to controls (P < 0.05).
  • The study identified specific types of oxidative DNA damage, including single/double strand breaks and oxidized purines/pyrimidines.

Conclusions:

  • Oxidative DNA damage is an early event in the multistep process of 4NQO-induced oral carcinogenesis.
  • The findings suggest that monitoring oxidative DNA damage could be valuable for assessing oral cancer risk.
  • This approach may be particularly relevant for high-risk populations, such as smokers and alcohol consumers.

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