Effect of alpha-difluoromethylornithine on DNA methylation in murine erythroleukaemic cells. Relationship to stimulation of induced differentiation.
Murine erythroleukaemic (MEL) cells cultured with alpha-difluoromethylornithine (DFMO) accumulated decarboxylated S-adenosylmethionine(decarboxylated AdoMet). In the absence of the inducer hexamethylenebisacetamide (HMBA), this accumulation of decarboxylated AdoMet was associated with a concomitant and proportional increase in DNA hypomethylation. In the presence of HMBA, DFMO, which stimulates the erythrodifferentiation of MEL cells, enhanced the differentiation-associated DNA hypomethylation. However, this differentiation-associated DNA hypomethylation was neither temporally nor quantitatively correlated with the accumulation of decarboxylated AdoMet in these cells. Therefore DFMO probably stimulates the HMBA-induced differentiation of MEL cells and the associated DNA hypomethylation via the effect of this drug on polyamine biosynthesis.
D000081:Acetamides / Q000494:pharmacology; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism*; D000518:Eflornithine / Q000494:pharmacology*; D004915:Leukemia, Erythroblastic, Acute / Q000378:metabolism*; D008745:Methylation; D051379:Mice; D012436:S-Adenosylmethionine / Q000378:metabolism; D013268:Stimulation, Chemical
D000081:Acetamides; D012436:S-Adenosylmethionine; D004247:DNA; C014026:hexamethylene bisacetamide; D000518:Eflornithine