Ras gene mutation is not related to tumour invasion during rat tongue carcinogenesis induced by 4-nitroquinoline 1-oxide

BACKGROUND: The aim of this study was to investigate whether mutations in the genes H-ras and K-ras were related to the mechanism of invasion as a result of the immunoexpression of H-Ras, Ki-67, alpha-smooth muscle actin (SMA) and vascular endothelial growth factor (VEGF) during 4-nitroquinoline 1-oxide (4NQO)-induced rat tongue carcinogenesis. METHODS: Male Wistar rats were distributed into three groups of 10 animals each and treated with 50 ppm 4NQO solution through their drinking water for 4, 12 and 20 weeks. Ten animals were used as negative control. RESULTS: Although no histopathological abnormalities were induced in the epithelium after 4 weeks of carcinogen exposure, Ki-67 was overexpresssed in the 'normal' oral epithelium. In pre-neoplastic lesions at 12 weeks following carcinogen exposure, the levels of Ki-67 were increased (P < 0.05) when compared to negative control. Ki-67, alpha-SMA and VEGF were also overexpressed in squamous cell carcinomas induced after 20 weeks of treatment with 4NQO. No significant statistical differences (P > 0.05) were found in H-ras protein expression for all experimental periods evaluated that corresponded to normal oral mucosa, hyperplasia, dysplasia and squamous cell carcinomas. In the same way, no mutations in H-ras or K-ras genes were found. CONCLUSIONS: Our results support the idea that expression of Ki-67 plays a crucial role during malignant transformation being closely related to neoplastic conversion of the oral mucosa cells. However, it seems that mutations in the ras genes are not involved to experimental tongue carcinogenesis induced by 4NQO.