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Systemic toxic effects during early phases of topical 4-NQO-induced oral carcinogenesis in rats
Ana Rita Ribeiro Barcessat1, Isaac Huang, Gustavo Davi Rabelo
1General Pathology Department, School of Dentistry, University of SãoPaulo, São Paulo, Brazil.
Background:
Most studies have demonstrated 4-NQO toxicity to oral epithelium during oral carcinogenesis induction, but systemic toxicity has been poorly addressed. The aim of this study was to describe the systemic effect of 4-NQO topical application during early phases of oral cancer induction.
Methods:
A 4-NQO propylene glycol ointment was topically applied on the rat tongue three times a week for 16 weeks. Local and systemic 4-NQO toxicity was evaluated by body weight gain, hematology, and serum chemistry analyses, histopathology, and proliferating cell nuclear antigen (PCNA) immunohistochemistry.
Results:
Significant reduction in body weight gain and in white blood cell count as well as significant increase in serum ALT and AST was observed after 16 weeks of 4-NQO topical application. Focal hepatic lobular necrosis, renal tubular degeneration, and decreased cellularity in the splenic white pulp were also detected.
Conclusions:
4-NQO topical application on the tongue of rats for 16 weeks seems to have caused hepatic, renal, and splenic toxicity. Potential systemic toxicity should be considered to monitor for variables that could interfere in topical oral carcinogenesis experiments.
Insights
Topical 4-NQO application in rats caused systemic toxicity, affecting the liver, kidneys, and spleen. This highlights the need to consider systemic effects in oral cancer research.
Area of Science:
- Toxicology
- Oral carcinogenesis
- Animal models
Background:
- 4-Nitroquinoline 1-oxide (4-NQO) is known for oral epithelium toxicity during cancer induction.
- Systemic toxicity of 4-NQO has been under-researched.
- Understanding systemic effects is crucial for accurate oral cancer research.
Purpose of the Study:
- To investigate the systemic toxicity of 4-NQO.
- To evaluate the effects of topical 4-NQO application on rat organs.
- To assess systemic impact during early oral cancer induction phases.
Main Methods:
- Topical application of 4-NQO ointment on rat tongues for 16 weeks.
- Evaluation of body weight, hematology, and serum chemistry.
- Histopathological and PCNA immunohistochemistry analyses for toxicity assessment.
Main Results:
- Significant reduction in body weight gain and white blood cell count.
- Increased serum ALT and AST levels, indicating liver damage.
- Histopathology revealed hepatic necrosis, renal degeneration, and splenic white pulp changes.
Conclusions:
- 16-week topical 4-NQO application induced hepatic, renal, and splenic toxicity in rats.
- Systemic toxicity must be considered in oral carcinogenesis experiments.
- Monitoring systemic variables is essential for reliable research outcomes.
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