Effect of α-difluoromethylornithine on DNA methylation in murine erythroleukaemic cells. Relationship to stimulation of induced differentiation

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Abstract
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.

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