Suppression of tumorigenicity mediated by 5-azacytidine and associated with increased chromosome number.
5-Azacytidine (5-azaC), a hypomethylating agent, was examined for the effect on a highly tumorigenic murine cell line, T984-15. While 20 of 20 untreated subclones of T984-15 produced tumors when injected into BALB/c nude mice, 14 of 15 T984-15 subclones that were treated for 24 hours with 5 micrograms 5-azaC/ml displayed suppressed tumorigenesis under identical conditions. Of the 14 clones that were suppressed, 12 were nontumorigenic and 2 showed a greatly increased latency. Chromosome analyses of 5-azaC-treated nontumorigenic clones revealed that, in contrast to untreated tumorigenic controls (median chromosome number 49-59), 9 of 10 5-azaC-treated nontumorigenic clones analyzed displayed an elevated chromosome complement (68-94 chromosomes/cell). The increase in chromosome number occurred progressively with time, following a single 24-hour 5-azaC treatment, indicating that 5-azaC was not selecting for a subpopulation of cells with an elevated chromosome complement. The evidence that the hypomethylating agent 5-azaC can suppress a cell's tumorigenic potential and that this suppression correlates with increased chromosome number suggests that 5-azaC modulates cellular phenotypes by mechanisms that involve alterations in a cell's chromosome complement.
D000818:Animals; D001374:Azacitidine / Q000627:therapeutic use*; D002460:Cell Line; D002875:Chromosomes / Q000032:analysis* / Q000187:drug effects; D004273:DNA, Neoplasm / Q000378:metabolism; D008745:Methylation; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000235:genetics
D004273:DNA, Neoplasm; D001374:Azacitidine