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.
D000818:Animals; D000956:Antigens, Viral / Q000032:analysis; D000957:Antigens, Viral, Tumor; D001374:Azacitidine / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D003599:Cytoskeleton / Q000648:ultrastructure; D004261:DNA Replication; D006183:H-2 Antigens / Q000032:analysis*; D008745:Methylation; D051379:Mice; D010960:Plasminogen Activators / Q000096:biosynthesis*; D011120:Polyomavirus / Q000502:physiology*; D013539:Simian virus 40 / Q000502:physiology; D013724:Teratoma; D014779:Virus Replication
D000956:Antigens, Viral; D000957:Antigens, Viral, Tumor; D006183:H-2 Antigens; D010960:Plasminogen Activators; D001374:Azacitidine