Assessment of bromodeoxyuridine-labeled S-phase cells in experimentally induced precancerous lesions in the rat's tongue

Abstract

Precancerous lesions and early invasive carcinomas were produced in the tongues of rats by oral administration of 0.001% 4-nitroquinoline 1-oxide in drinking water. The distribution and densities of S-phase cells were then studied in an attempt to clarify the mechanism of carcinogenesis from the viewpoint of cell cycle. Bromodeoxyuridine (BrdU)-labeled S-phase cells were demonstrated by an indirect peroxidase method, using anti-BrdU monoclonal antibody, and their percentage was determined as the labeling index (LI). The average BrdU LI was significantly higher in the precancerous lesions than in the normal epithelium. There was a wide range of LI found in cells showing such changes as hyperplasia, hyperparakeratosis, dysplasia and papilloma, but the differences among them were not significant. These findings also showed that there could be considerable differences in proliferative activity among lesions of the same grade, while the difference in histology did not mean a difference in proliferative activity. Additionally, many BrdU-labeled cells were seen in a few layers over the basement membranes of non-cancerous lesions immediately adjacent to early invasive carcinoma, suggesting that these layers had a higher possibility for advancing to early invasive carcinoma.

Induction of focal epithelial hyperplasia in tongue of young bk6-E6/E7 HPV16 transgenic mice

“…Although FEH is a benign, asymptomatic disease and it has been related with low-risk HPV types 13 and 32 (Carlos and Sedano 1994;SeguraSaint-Gerons et al 2005), these alterations are suggestive of a possible premalignant status in tongue of transgenic mice. Interestingly, we have found FEH development in both dorsal and ventral surfaces of tongue obtained from transgenic mice, in comparison with other rodent models in which tongue lesions (dysplasia and neoplasm) were chemically induced and observed only in the dorsal surface (Tanaka et al 1992(Tanaka et al , 1993Yamamoto et al 1994;Hong et al 2007). Since HPV infection can be frequently detected in tongue premalignant dysplastic lesions, E6/E7 proteins might be expected to play a role early in oral carcinogenesis (Blons and Laurent-Puig 2003;Griep et al 1993;Ide et al 2001).…”