The object of this project is to examine the regulation of gene expression associated with cellular differentiation in two experimental model systems; 1) the human promyelocytic leukemia cell line, HL60, and 2) the rat hepatoma cell lines, Reuber and 7777. The results obtained in the HL60 cell line study include a functional assocaition of c-myc RNA levels with the differentiation state of the cell. Specifically, expression of c-myc is almost exclusively associated with the promyelocytic status of the HL60 cells and this expression is repressed during differentiation of the promyelocytes to monocytes. Conversely N-ras specific transcription is eff-ted to no significant extent during differentiation specific or growth specific treatment. The results obtained and experiments in progress in the rat hepatoma cell study include an albumin specific gene response following treatment with butyric acid or inhibitors of ADP-ribosylation. This response was independent of the """"""""differentiation state"""""""" of the cells, as measured by alpha-fetoprotein (AFP) or albumin production, since the albumin specific response was present in the high albumin, high AFP producer cell line (Reuber) or the low albumin, low AFP producer line (7777). The AP gene was not affected by this treatment protocol in either cell line.
