# A comparative study of the effects of three modes of 4-Nitroquinoline N-oxide induction of Sprague Dawley rats in animal models of oral leukoplakia

**Authors:** Mengyu Jiao, Peiyan Wang, Xiaofei Yu, Changqing Yuan, Pei Sun, Junjie Tong, Tianlu Wang, Jing Deng, Hui Zhang

PMC · DOI: 10.1515/biol-2025-1263 · Open Life Sciences · 2026-01-28

## TL;DR

This study compares methods for creating an oral leukoplakia model in rats using 4NQO and finds that drinking 0.002% 4NQO is the safest and most effective method.

## Contribution

The study identifies a safer and simpler method for inducing oral leukoplakia in rats using 4NQO.

## Key findings

- The 0.002% 4NQO drinking group showed no mortality and the best overall condition.
- All three groups exhibited pathological features consistent with human oral leukoplakia.
- The drinking method is recommended for its simplicity and safety.

## Abstract

Animal models are essential for advancing disease research. However, models for oral leukoplakia (OLK) remain relatively underexplored. This study sought to identify an optimal strategy for establishing a rat OLK model using 4-nitroquinoline 1-oxide (4NQO). The experimental groups included 0.002 % 4NQO drinking, 0.5 % 4NQO painting, and 0.002 % 4NQO drinking combined with 0.5 % 4NQO painting groups. Morphological changes, behavioral status, body weight, water intake and mortality were monitored. Histopathological features of rat tongue lesions were compared with those of human OLK. Drinking combined with painting group showed a large number and area of white lesions on tongue mucosa. The modeling effect of OLK in drinking group showed no significant difference from other groups, and the rats exhibited the best overall condition with no mortality. Painting group showed intermediate efficacy. Pathological manifestations in three groups were consistent with human OLK. Given its simplicity and superior safety profile, the 0.002 % 4NQO drinking protocol is recommended as the preferred approach for OLK model establishment.

## Linked entities

- **Chemicals:** 4-nitroquinoline 1-oxide (PubChem CID 5955), 4NQO (PubChem CID 5955)
- **Diseases:** oral leukoplakia (MONDO:0004844)

## Full-text entities

- **Genes:** TP53 (tumor protein p53) [NCBI Gene 7157] {aka BCC7, BMFS5, LFS1, P53, TRP53}, p53-ps (Wistar clone pR53P1 p53 pseudogene) [NCBI Gene 301300]
- **Diseases:** hyperplasia (MESH:D006965), intestinal obstruction (MESH:D007415), gastrointestinal irritation (MESH:D005767), oral mucosal disorders (MESH:D013280), epithelial hyperplasia (MESH:D017573), NM (MESH:C536816), death (MESH:D003643), OLK (MESH:D007972), carcinogenic (MESH:D011230), metabolic abnormalities (MESH:D008659), Tongue lesions (MESH:D014060), dysplastic leucoplakia (MESH:D004416), OSCC (MESH:D000077195), weight gain (MESH:D015430), Oral Diseases (MESH:D009059), epithelial dysplasia (MESH:C567703), alopecia (MESH:D000505), oral cancer (MESH:D009062), oral carcinogenesis (MESH:D063646), mucosal irritation (MESH:D001523), OLP (MESH:D017676), cancer (MESH:D009369), inflammatory (MESH:D007249), oral mucosal ulcers (MESH:D019226), dysplasia (MESH:D015792)
- **Chemicals:** benzopyrene (MESH:D001580), eosin (MESH:D004801), H (MESH:D006859), formalin (MESH:D005557), citrate (MESH:D019343), Diaminobenzidine (-), hydrogen peroxide (MESH:D006861), H &amp; E (MESH:D006371), Haematoxylin (MESH:D006416), dimethylbenzanthracene (MESH:D015127), Water (MESH:D014867), 4-Nitroquinoline N-oxide (MESH:D015112), Paraffin (MESH:D010232)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116], Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090]

## Full text

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## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12917560/full.md

## References

26 references — full list in the complete paper: https://tomesphere.com/paper/PMC12917560/full.md

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Source: https://tomesphere.com/paper/PMC12917560