EARLY GENETIC CHANGES IN IN VIVO CARCINOGENESIS

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Early Genetic Changes in In Vivo Carcinogenesis Carcinogenesis is a multi-step process and the cooperative interaction of two or more genes is believed to be involved. In an in vivo model of carcinogenesis, the role of two genes cHa-ras and cerb B will be examined in 7, 12 dimethylbenzanthracene (DMBA) induced hamster buccal pouch epithelium. The mRNA studies have shown that there is a sequential and stage specific overexpression of the two genes. In this investigation I propose to identify the protein products of cHa-ras and cerb B genes, establish the cellular compartmentalization of the genes' proteins, have an overview of the cHa-ras and cerb B expressing cells in the total population, and establish the temporal correlation between gene expression and histopathological changes in the HBPE tissues. There studies will be conducted by immunoflourescent technique using single as well as double primary antibodies and one or two more immunoreporters respectively. In addition, polymerase chain reaction will be helpful to amplify certain regions of the cHa-ras gene believed to contain mutation (s), which can be correlated to stage specific changes in cells and tissues. It has been proposed that the activation of the cHa-ras gene may generate the initial signal which is followed by activation of cell-proliferation-associated proto-oncogenes or deletion of suppressor genes. The later genes are involved in the progression of the ras-initiated cells to continuous proliferation and malignancy.