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.
Abstract:
The aim of this study was to investigate oxidative DNA damage during 4-nitroquinoline 1-oxide (4NQO)-induced rat tongue carcinogenesis. For this purpose, male Wistar rats were distributed into three groups of 10 animals each and treated with 50 ppm 4NQO solution through their drinking water for 4, 12, and 20 weeks. Ten animals were used as negative control. The alkaline Comet assay modified with lesion-specific enzymes was used to detect single and double strand breaks, labile sites (SBs), and oxidised purines and pyrimidines. Although no histopathological abnormalities were induced in the epithelium after 4 weeks of carcinogen exposure, oxidative DNA damage was detected in the 'normal' oral epithelium. In pre-neoplastic lesions and squamous cell carcinomas induced after 12 and 20 weeks following carcinogen exposure, respectively, oxidative DNA damage was also increased (P < 0.05) when compared to negative control. In conclusion, our results suggest that oxidative DNA damage is an early event during multistep carcinogenesis assay induced by 4NQO. This kind of approach should be considered to persons with high risk of oral cancer, such as in smokers or alcohol consumers.
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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