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

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.