MNU AFFECTS MOUSE ERYTHROLEUKEMIA CELL-DIFFERENTIATION AT SUB-CYTOTOXIC DOSES

MNU is a potent carcinogen and mutagen to various tissues. Molecular e vents during differentiation show particular sensitivity to MNU exposu re. We have investigated the mouse erythroleukemia (MEL) cell differen tiation in response to DMSO and the influence of subcytotoxic doses of MNU on this process to assess the role of MNU on the course of differ entiation and specific gene expression in a single cell type. Differen tiation was followed by determining the extent of hemoglobinization an d beta-globin gene expression, which are representative measures of re d cell maturation. In this study we have shown a delay and decrease in the extent of MEL cell differentiation by MNU exposure at the time of induction to differentiate, even at sub-lethal MNU concentrations. On ce the differentiation process was initiated, exposure to MNU at sub-l ethal doses showed a significantly smaller effect on the molecular cou rse of events. Pre-treatment of MEL cells with MNU before DMSO inducti on did not affect differentiation. The MNU-induced delay in differenti ation was reflected in the delayed appearance of beta-globin transcrip ts during the first 12 h post induction. However, transcription could not account for reduced hemoglobinization of the MNU-treated cells at 48 and 72 h post induction.