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

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.