4nqo-Induced Changes in Rat Oral and Gastrointestinal Tract Mucosa

4-nitroquinoline-N-oxide (4NQO) administered via drinking water is a known model of oral carcinogenesis in rats. Objective: To evaluate the effect of 4NQO on the rat tongue and gastrointestinal tract mucosa. Materials and Methods: The study design consisted of 50 Wistar rats administered 0.001% 4NQO via the drinking water and 10 control rats drinking tap water. Rats were sacrificed at two weeks intervals for 37 weeks. The tongue, esophagus, stomach and colon were dissected and processed for routine histopathologic examination. Hematoxylin and eosin (H&E) stained sections were analyzed for histomorphologic and histomorphometric parameters. Results: Examination of H&E stained sections of tongue mucosa revealed progression from simple hyperkeratosis to dysplasia and ultimately to invasive squamous cell carcinoma. Dysplasia was first observed after 4 weeks, squamous cell carcinoma (SCC) after 27 weeks. In the esophagus, hyperkeratosis was the most prevalent change, with mild dysplasia observed after 13 weeks, and carcinoma in situ after 35 weeks. In the forestomach changes of hyperkeratosis and mild dysplasia were noticed, beginning after 13 weeks. In the glandular stomach and colonic mucosa only atrophic changes were noticed, beginning at week 30 in the glandular stomach and 13 in the colon. With the exception of the tongue, invasive carcinoma did not develop in any other area of the GIT. Conclusions: The earliest and most severe changes induced by 4NQO were observed in the tongue, resulting in invasive SCC in all animals within 6 months. Less severe and delayed mucosal changes were found in the rest of the gastrointestinal tract, with decreasing severity along the passage.