Experimental induction of irreversible precancerous changes in the palatal epithelium of the rat

The development of irreversible precancerous changes in the palatal mucosa of the rat was studied macroscopically and histologically after painting the palate 3 times a week with 0.5% 4-nitroquinoline-N-oxide for 1-22 weeks. Control animals were painted with the solvent propylene glycol. After the application periods, the spontaneous development of premalignant epithelial changes and carcinomas was recorded by repeated biopsy procedures. Short application periods (1-6 weeks) were consistently followed by prolonged expectancy periods (51-80 weeks) before the development of carcinomas. Comparably long application periods (more than 12 weeks), however, induced carcinomas after relatively short expectancy periods (8-21 weeks). The total experimental periods (application plus expectancy periods) for animals painted for more than 12 weeks were frequently less than 1/2 of that for animals painted for 1-6 weeks. All experimentally induced tumours represented highly differentiated squamous cell carcinomas with excessive keratin formation. They were consistently preceded by different stages of epithelial dysplasia. Advanced carcinomatous changes were frequently not visible macroscopically. Irreversible precancerous transformation had already occurred in epithelium at early hyperplastic, non-dysplastic stages.