Epithelial dysplasia and squamous cell carcinoma of the Wistar rat palatal mucosa: 4NQO model.

Abstract

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.