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Modeling Oral-Esophageal Squamous Cell Carcinoma in 3D Organoids
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Optimizing Preclinical Models for Oral Cancer: The Influence of 4NQO Administration Routes on Tumor Development.

Jolien Van den Bosch1, Nuran Caz1, Sandrina Martens1

  • 1Laboratory for Functional Imaging and Research on Stem Cells (FIERCE Lab), Biomedical Research Institute (BIOMED), Hasselt University, 3950 Diepenbeek, Belgium.

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|July 12, 2025
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Summary

The 4-Nitroquinoline 1-oxide (4NQO) rat model effectively mimics oral squamous cell carcinoma (OSCC) progression. Oral administration via drinking water is superior for preclinical research, inducing earlier and more advanced tumors.

Keywords:
4-Nitroquinoline 1-oxideex vivo MRIhistopathologyoral squamous cell carcinomarat model

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Area of Science:

  • Oncology
  • Preclinical Cancer Models
  • Translational Research

Background:

  • Oral squamous cell carcinoma (OSCC) is a prevalent cancer with a complex progression from hyperplasia to invasive stages.
  • Developing accurate animal models for OSCC, particularly those capturing early and advanced disease, remains a significant challenge.
  • The 4-Nitroquinoline 1-oxide (4NQO) model is recognized for its potential to recapitulate all phases of OSCC development.

Purpose of the Study:

  • To comprehensively characterize the 4-Nitroquinoline 1-oxide (4NQO) rat model for oral squamous cell carcinoma (OSCC).
  • To compare the efficacy of two distinct 4NQO administration methods: oral (drinking water) and topical application.
  • To evaluate the suitability of the 4NQO model for preclinical testing of novel OSCC therapeutics.

Main Methods:

  • The study utilized a 4NQO rat model over an eight-month period.
  • Two administration routes were tested: 4NQO in drinking water and topical 4NQO application.
  • Histopathological analysis and ex vivo magnetic resonance imaging (MRI) were performed monthly to monitor tumor development and progression.

Main Results:

  • Carcinoma in situ (CIS) developed by three months with drinking water administration, progressing to invasive squamous cell carcinoma (ISCC) by six months.
  • Topical application induced CIS by eight months but did not result in ISCC formation.
  • The drinking water group, especially with tongue involvement, exhibited earlier CIS, larger lesions, and deeper invasion compared to topical application.
  • Proliferative activity was high in dysplastic lesions but decreased upon invasion.
  • MRI successfully visualized macroscopic tumor lesions, correlating with histological findings.

Conclusions:

  • The 4NQO rat model, particularly when administered via drinking water, accurately replicates the histopathological progression of human oral squamous cell carcinoma (OSCC).
  • This validated model provides a robust platform for preclinical evaluation of therapeutic strategies targeting OSCC.
  • The findings underscore the importance of the administration method in optimizing the 4NQO model for translational research.