To understand the molecular mechanism of chemically-induced oral carcinogenesis is the primary objective of this proposal. An in vivo animal model (hamster cheek pouch)system, in which dimethylbenzanthracene (DMBA)-induced tumor formation has been well established, is utilized in this investigation. The various clinical stages of tumor development in hamster cheek pouch following DMBA treatment, has been clearly defined. An epidermoid carcinoma cell line (HCPC 1) has been established from such a hamster cheek pouch tumor. Our preliminary results reveal that the oncogene Ha-ras is activated and c-erb B and c-sis genes are amplified in this oral carcinogenesis system during transition of the cell from normal to the neoplastic state. Experimental approaches will be made to define the stage of tumor development, in which the activation and amplification of these oncogenes initiate. Possible activation/inactivation of other cellular oncogenes will be tested. The role of these oncogene/s in the development of DMBA-induced oral cancer will be verified. The mechanism of activation of Ha-ras gene or any other oncogenes will be investigated. A general approach will be made to identify activation/inactivation of other cellular genes along with progression of tumorigenesis process. A correlation between the clinical changes (morphological and histopathological) and altered molecular events events during the development of DMBA induced hamster cheek pouch tumor, will be established. This criteria may provide a diagnostic tool for the early detection of oral cancer. Modern molecular biological and recombinant DNA technology, which are already established in this laboratory, will be utilized to achieve these goals.
