Nauta J M, Roodenburg J L, Nikkels P G, Witjes M J, Vermey A
Department of Oral and Maxillofacial Surgery, University Hospital Groningen, The Netherlands.
Head Neck. 1996 Sep-Oct;18(5):441-9. doi: 10.1002/(SICI)1097-0347(199609/10)18:5<441::AID-HED7>3.0.CO;2-5.
The carcinogen 4-nitroquinoline 1-oxide (4NQO) has been used in several studies concerning experimental oral carcinogenesis to induce squamous cell carcinoma in the palatal mucosa of rats, whereas limited attention has been paid to preceding premalignant mucosal changes. The aim of this study was to describe the macroscopic and microscopic changes of the rat palatal mucosa treated with 4NQO as a function of the application time of this carcinogen.
The carcinogen 4NQO was applied to the palatal mucosa of male Wistar rats three times a week for 2-26 weeks. The Epithelial Atypia Index (EAI) was used to quantify the degree of dysplasia induced by the application of 4NQO for various time intervals.
This study shows that the EAI increases as a function of the application time. As soon as 2 weeks following application of the carcinogen, dysplastic alterations in the mucosa were observed. The extent and grade of the dysplastic changes increased with time. At week 26, squamous cell carcinoma developed. In rats in which the application of 4NQO was discontinued earlier, the application period appeared to be in inverse proportion to the latency period i.e., the period between the last application of the carcinogen and the first clinical sign of squamous cell carcinoma. This emphasizes the premalignant character of the induced epithelial changes, because in all the rats squamous cell carcinoma eventually developed.
From this study, we concluded that the 4NQO rat palate model is a proper model in which both premalignant epithelial lesions and squamous cell carcinoma of the oral mucosa can be studied.
致癌物4-硝基喹啉-1-氧化物（4NQO）已用于多项关于实验性口腔致癌作用的研究，以诱导大鼠腭黏膜发生鳞状细胞癌，而对癌前黏膜前期变化的关注较少。本研究的目的是描述用4NQO处理的大鼠腭黏膜的宏观和微观变化与该致癌物应用时间的关系。
致癌物4NQO每周三次应用于雄性Wistar大鼠的腭黏膜，持续2 - 26周。上皮异型性指数（EAI）用于量化在不同时间间隔应用4NQO所诱导的发育异常程度。
本研究表明，EAI随应用时间增加。在应用致癌物后仅2周，就观察到黏膜发育异常改变。发育异常变化的程度和等级随时间增加。在第26周时，发生了鳞状细胞癌。在较早停止应用4NQO的大鼠中，应用期似乎与潜伏期成反比，即致癌物最后一次应用与鳞状细胞癌的首个临床体征之间的时间间隔。这强调了所诱导的上皮变化的癌前特征，因为在所有大鼠中最终都发生了鳞状细胞癌。
从本研究中，我们得出结论，4NQO大鼠腭模型是一个合适的模型，可用于研究口腔黏膜的癌前上皮病变和鳞状细胞癌。
