The long term goal of the proposed research is to study induced and spontaneous changes in expression of the epidermal phenotype within the framework of a progressive and evolving transformation program initiated by infection of keratinocytes with the oncogenic virus, SV40. We will approach this goal from two distinct, but interrelated directions: 1) by studying spontaneous, transformation-related changes in the patterns of synthesis of keratin and involucrin, two well characterized phenotypic proteins, as well as induced changes in the synthesis of these proteins and histologic expression of the epidermal phenotype using chemicals (azacytidine and purine analogs) and growth in vivo as effectors, 2) by studying structural differences in the state of the viral genome (i.e. free vs. integrated forms) is clonal populations with a view towards correlating these differences with variation in phenotype expression among the clonal populations examined. We will also use interferon in an attempt to reduce the cellular content of viral DNA to determine how 'curing' the cells of the virus will affect phenotype expression. The results of these experiments will be considered in the context of a model of the evolution of cells to a malignant state.
