4NQO饮水诱发大鼠舌癌模型的建立

A rat model of tongue mucosa squamous cell carcinoma induced by oral administration of 4NQO in drinking water

目的 建立与人口腔环境相近的大鼠舌癌模型。方法 0 0 0 2 % 4 硝基喹啉 1 氧化物( 4NQO)饮水喂养SD大鼠 9～ 3 2周 ,肉眼及组织学观察癌变全过程。结果 随致癌剂作用时间延长 ,大鼠舌背后部粘膜相继出现白色斑块、溃疡、糜烂、乳头状增生等改变。 9周后 80 0 %大鼠舌背粘膜表现为单纯性上皮增生 ,2 0 0 %为轻中度异常增生 ;13周后 66 6%为轻中度异常增生 ,3 3 3 %为重度异常增生 ;16周后 5 5 5 %为重度异常增生 ,4 4 4 %为原位癌 ;3 2周后 12 5 %为重度异常增生 ,12 5 %原位癌 ,75 0 %为侵袭性高分化鳞癌 ;用药 9、13、16周 ,停药后观察到 3 2周时 ,舌癌发生率分别为5 0 0 %、62 5 %、77 8%。未见远处转移。结论 4NQO饮水诱发大鼠舌癌生长缓慢、潜伏期较长 ,致癌过程和组织病理学特征与人口腔癌相似 ,方法简便 ,靶器官代表性强 ,为口腔癌的发生机制研究和防治药物筛选提供了较理想的动物模型。

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