Objective: To establish a more realistic animal model for oral carcinogenesis which reveals histological and immunological characteristics similar to the human counterpart.
Methods: 0.002% 4-nitroquinoline 1-oxide (4NQO) in drinking water was administered orally to SD rats for 9-32 weeks. Then the rats were killed and their tongues were removed for histological assessment.
Results: Gross changes included leukoplakia, erosion, ulcer and papillary appearance on the dorsum of the posterior tongue were present during carcinogenesis. Their corresponding histopathological findings ranged from hyperplasia (HP), mild-moderate dysplasia (mmDP), severe dysplasia (sDP) and in situ carcinoma (ISC) to well-differentiated invasive squamous cell carcinoma (SCC). The severity of lesions corresponded to the duration of administration. The tongues in rats treated with 4NQO for 9 weeks showed HP (80.0%) and mmDP (20.0%); those for 13 weeks showed mmDP (66.6%) and sDP (33.3%); those for 16 weeks showed sDP (55.5%) and ISC (44.4%); and those for 32 weeks showed sDP (12.5%), ISC (12.5%) and SCC (75.0%). The incidence of tongue cancer in rats treated with 4NQO for 9 weeks, 13 weeks, 16 weeks and then observed for 32 weeks was 50.0%, 62.5%, and 77.8%, respectively. No metastases were found.
Conclusion: 4NQO reliably produced preneoplastic and neoplastic tongue mucosa lesions, which morphologically and histologically mimic human oral carcinogenesis. The rat tongue, a target organ of 4NQO, is not an immunologically privileged site like the hamster buccal pouch. Thus, the model should be appropriate to study molecular mechanism of neoplastic transformation and to assess new treatment modalities of premalignant and malignant lesions of the human oral cavity.