Indirect induction of erythroid differentiation in mouse Friend cells: evidence for two intracellular reactions involved in the differentiation.

The mechanism of in vitro erythroid differentiation in mouse Friend cells was studied by employing cell fusion between two genetically marked Friend cells and other nonerythroid cells, including BHK (baby hamster kidney) and FM3A (mouse mammary gland) cells. We were able to induce erythroid differentiation indirectly by fusing Friend cells that had been exposed briefly to dimethyl sulfoxide prior to fusion with nonerythroid cells that had been treated with ultraviolet light (or other DNA-damaging agents). The results suggest that two distinct reactions are involved in erythroid differentiation in Friend cells in vitro. One reaction, originating from the damaged DNA (or inhibition of DNA replication as a consequence), exhibits an inducible nature, is nonspecific to Friend cells, and is trans-acting. The other reaction is specific to Friend cells and most likely is cis-acting. We also present evidence from the cell fusion experiments that a typical tumor promoter, 12-O-tetradecanoylphorbol 13-acetate, inhibits erythroid differentiation by affecting the latter reaction. The biological significance of these findings is discussed.