We are probing the relationship of oncogene activation as the stimulus to the phenotypic expression of transformation. It has become clear in recent years that the mechanism of cancer formation by environmental chemicals involves complex genetic alterations related to the binding of metabolically activated chemical intermediates with cellular macromolecules. While genes are the template for mutation, translation of oncogenes into active proteins are critical for phenotypic expression of mutation and cancer. Since cancer is the somatic expression of a genetic event we would like to understand the cascade of biochemical steps that steer the initiated cell through the malignant transformation process. The advent of multiple gel technology and the concomitant use of computerized image analysis has enabled a more sophisticated approach to the analysis of the enormous amount of bio-molecular information present in 2D Gels for both structural identification and comparative pattern analysis of proteins. The burgeoning gene sequence databases are a valuable adjunct to our research since it offers the possibility of retracing critical proteins identified from gels back to the gene of origin. This can be accomplished by """"""""backtranslating"""""""" genes to determine the triplet code template nucleotide sequence and searching via special algorithms to match the deduced sequence against known genes. Since the transformed phenotype is the result of aberrant regulatory and/or structural proteins we are advancing into identifying both the presence of oncoproteins and suppressor proteins as a result of chemical treatment as well as the changes in the cellular protein profile as a response to the presence of active oncoproteins.
