Oral epithelial atypia and acantholytic dyskeratosis in rats painted with 4-nitroquinoline N-oxide

Oral epithelial atypia and foci of acantholytic dyskeratosis (FAD) were investigated in 54 rats treated with the carcinogen 0.5% (w/v) 4-nitroquinoline-N-oxide in propylene glycol and in 18 rats treated with propylene glycol only. The palate of each animal was painted 3 times weekly for up to 9 months and rats were killed at monthly intervals. A gradual significant increase in the epithelial atypia indices of the palatal and lingual tissues (anterior and posterior of the intermolar tubercle) was observed with a maximum value of 17-22 of a possible 75 at 28-32 weeks. No significant differences were noted between the atypia indices of the palatal and lingual tissues. FAD were not evident in the palate or lingual tissues before 12 weeks and 16-24 weeks, respectively, and although the palate consistently showed more FAD compared with the lingual tissues the differences were not significant. Features of epithelial atypia and FAD were absent in the 18 control rats treated with propylene glycol only and in 8 untreated control animals. At 28 weeks of 4NQO treatment 2 of 5 rats, at 32 weeks 3 of 4 rats and at 36 weeks 3 of 3 rats had developed infiltrating squamous cell carcinomas in either/both the palate or tongue. The results suggest that epithelial dysplasia and acantholytic dyskeratosis may be late morphological features of a more fundamental change occurring earlier in the process of tumour development.