MNU affects mouse erythroleukemia cell differentiation at sub-cytotoxic doses.
MNU is a potent carcinogen and mutagen to various tissues. Molecular events during differentiation show particular sensitivity to MNU exposure. We have investigated the mouse erythroleukemia (MEL) cell differentiation 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 differentiation and specific gene expression in a single cell type. Differentiation was followed by determining the extent of hemoglobinization and beta-globin gene expression, which are representative measures of red 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. Once the differentiation process was initiated, exposure to MNU at sub-lethal doses showed a significantly smaller effect on the molecular course of events. Pre-treatment of MEL cells with MNU before DMSO induction did not affect differentiation. The MNU-induced delay in differentiation was reflected in the delayed appearance of beta-globin transcripts 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.
Sun-Hoffman
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Department of Microbiology, University of Nevada, Reno 89557, USA.
Winicov
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I
D000818:Animals; D015152:Blotting, Northern; D002273:Carcinogens / Q000633:toxicity*; D002452:Cell Count / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D005786:Gene Expression Regulation; D005914:Globins / Q000235:genetics; D004915:Leukemia, Erythroblastic, Acute / Q000473:pathology*; D008770:Methylnitrosourea / Q000633:toxicity*; D051379:Mice; D008811:Mice, Inbred DBA; D012334:RNA, Neoplasm / Q000302:isolation & purification; D011994:Recombinant Proteins; D013997:Time Factors; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured / Q000187:drug effects*
D002273:Carcinogens; D012334:RNA, Neoplasm; D011994:Recombinant Proteins; D008770:Methylnitrosourea; D005914:Globins; D004121:Dimethyl Sulfoxide