An animal model for oral cancer

Human head and neck squamous cell carcinogenesis (SCC) is a common malignancy that appears to be related to continuous exposure to putative carcinogens or promoters such as tobacco and alcohol. To understand the mechanisms of the development of head and neck cancer and to test the efficiency of new therapeutic approaches, the characterization of an animal model system is necessary. The check-pouch carcinogenesis model in Syrian golden hamsters is probably the best known animal system that is most closely comparable with the development of premalignant and malignant lesions in human oral cancer. Furthermore, it is one of the most well-characterized animal system models for SCC. Our first approach to understanding the cellular and molecular changes that occur in the hamster cheek-pouch carcinogenesis process was to compare this model to the mouse-skin system, in which a number of critical events have been well characterized. We examined the sequential expression of hyperplasia, micronucleated cells, ornithine decarboxylase activity, polyamine levels, transglutaminase I activity, epidermal growth factor receptor levels, expression of several keratins, gamma-glutamyl transpeptidase, and nucleolar organizer regions. We suggest that these markers can be used to understand mechanisms of carcinogenesis and, in addition, can serve as alternative shorter end points in studies of chemoprevention. We also present preliminary molecular studies in the experimental oral model. We obtained a partial sequence of exon 2 of the Ha-ras gene and detected an A182----T transversion in codon 61 in hamster cheek-pouch SCC induced by 7,12-dimethylbenz(a)anthracene.