Effect of 5-azacytidine treatment on mouse embryonal carcinoma cells.

Several properties of embryonal carcinoma (EC) cell lines, such as multipotent PCC4-aza-1 cells and nullipotent F9 cells originating from murine teratocarcinoma cells, were examined after treatment with 5-azacytidine, which produces undermethylated DNA. Drug-treated PCC4-aza-1 cells exhibited morphological changes and differentiated, whereas azacytidine-treated F9 cells displayed no detectable morphological change. After treatment with 5 azacytidine, PCC4-aza-1 cells, whether or not they differentiated, as well as F9 cells, became permissive for polyoma even though both cell types are usually resistant to polyoma. In contrast, only the differentiated azacytidine-treated PCC4-aza-1 cells became sensitive to SV40 infection, i.e., synthesized T antigen, despite the resistance normally shown by such cells to this viral infection. In some PCC4-aza-1 and F9 cells, drug treatment induced expression of H2 antigen but did not derepress plasminogen activator synthesis. These results suggest that undermethylation of certain cellular genes in PCC4-aza-1 and F9 cells is correlated with the establishment of Py permissivity, SV40 sensitivity, H2 antigen expression, and the triggering of a differentiation process. The relationship between the expression of these characters and differentiation is discussed.