Avian leukosis virus induces a bursal dependent B cell lymphoma in the chicken. A rare histopathological lesion, the transformed follicle, appears in the bursa shortly after infection. It has been proposed that this lesion is a preneoplastic stage required for the development of the lymphoma. The long range goal of this project is to define the biochemical characteristics that distinguish the preneoplastic cell from the normal cell. The preneoplastic cell represents an intermediate stage of neoplastic development that deserved considerable study. Analysis of the transformed follicle should provide information fundamental to an appreciation of the biochemical and physiological conditions that increase the propensity of a cell to develop into a tumor. The cells within the ALV-induced transformed follicle will be characterized by in situ hybridization and immunochemical analysis in order to identify the presence of specific mRNAs and proteins. A recombinant retroviral vector will be used to evaluate the hypothesis that the expression of c-myc results in the formation of the preneoplastic event. cDNA hybridization probes specific for the transformed follicle and the tumor will be developed by subtractive hybridization in order to identify clones within a cDNA library. These genes, expressed preferentially in preneoplastic or neoplastic tissue, will be characterized and the sequences encoding the protein inserted into retroviral vectors. Virus prepared from these vectors will be used in an in vivo assay to assess the functional significance of the expression of these genes in establishing the preneoplastic state.
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