[Cell differentiation action of 4'-epi-adriamycin in WEHI-3B myelomonocytic leukemia cells]

We studied the effect of 4'-epi-adriamycin on the differentiation of WEHI-3B (D+) murine myelomonocytic leukemia cell line (parent line) and WEHI-3B-MIT-R subline resistant to induction of differentiation by mitoxantrone. WEHI-3B(D+) cells were differentiated into mature granulocytes in suspension culture when exposed to 4'-epi-adriamycin regardless of the cell densities. The maximum differentiation rate was produced by 50 nM 4'-epi-adriamycin; at this concentration, approximately 40% of the cell population expressed a differentiated phenotype, as assessed by their ability to reduce nitroblue tetrazolium Induction of differentiation was observed by 4'-epi-adriamycin even at low cell densities (less than 10(5)/ml) that excluded the effects of autoinduction of differentiation. WEHI-3B-MIT-R cell line, which have a capacity of G-CSF-induced differentiation, was cross-resistance to 4'-epi-adriamycin. These results suggest that the mechanism of action differs from that of the induction of differentiation by G-CSF (which is known to show the activity by the secondary autoinduction of differentiation) and the differentiation induction is due to the direct action of 4'-epi-adriamycin.