Tumor promoters inhibit spontaneous and induced differentiation of murine erythroleukemia cells in culture.

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Abstract
Addition of the potent tumor promoter, 12-O-tetradecanoyl-phorbol-13-acetate (TPA), to mouse erythroleukemia cell lines in suspension cultures inhibited spontaneous differentiation and differentiation induced by hexamethylene bisacetamide (HMBA), dimethyl sulfoxide or butyric acid. Inhibition was unrelated to cytotoxicity and was reversible. When several plant diterpenes were tested, there was a positive correlation between tumor promoting activity and inhibition of differentiation. TPA inhibited HMBA induced differentiation only if added prior to the time of commitment to differentiation, as assayed by scoring for differentiation after transfer of cells from HMBA to fresh medium without HMBA. TPA mediated inhibition of differentiation was associated with a decrease in globin mRNA accumulation.