Growth inhibition and differentiation induction in murine erythroleukemia cells by 4-hydroxynonenal

4-Hydroxynonenal (HNE) is one of the major end products of lipid peroxidati on. Here we show that the exposure of murine erythroleukemia (MEL) cells to 1 muM HNE, for 10.5 h over 2 days, induces a differentiation comparable wi th that observed in cells exposed to DMSO for the whole experiment (7 days) . The exposure of MEL cells for the same length of time demonstrates a high er degree of differentiation in HNE-treated than in DMSO-treated MEL cells. The protooncogene c-myc is down-modulated early, in HNE-induced MEL cells as well as in DMSO-treated cells. However, ornithine decarboxylase gene exp ression first increases and then decreases, during the lowering of the prol iferation rate. These findings indicate that FINE, at a concentration physi ologically found in many normal tissues and in the plasma, induces MEL cell differentiation by modulation of specific gene expression.