Suppression of hematopoietic-progenitor-cell proliferation by ethanol and acetaldehyde.
The effects of alcohol on bone marrow are not well understood. We measured the influence of ethanol and its metabolite, acetaldehyde, on the in vitro proliferation of hematopoietic progenitor cells from mice and human beings. Colony formation by both early and late erythroid progenitor cells was suppressed by concentrations of ethanol (0.05 to 0.2 per cent) that are easily achieved in vivo. The corresponding suppressing concentration of acetaldehyde was 0.001 per cent. In contrast, suppression of granulocyte/macrophage progenitor cells required 3.0 per cent ethanol or 0.03 per cent acetaldehyde. Spleen colony formation by pluripotent stem cells was resistant to concentrations of ethanol and acetaldehyde that suppressed in vitro colony formation of committed myeloid and erythroid progenitor cells by 50 per cent. The suppression of both myeloid and erythroid colony formation was partially reversed by supplementing the cultures with folinic acid or pyridoxine. These data provide an explanation for the preferential suppression of erythropoiesis observed clinically in ethanol abuse. They also suggest that acetaldehyde has a role in ethanol-mediated bone-marrow suppression.
D000079:Acetaldehyde / Q000494:pharmacology*; D000818:Animals; D001853:Bone Marrow / Q000187:drug effects; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D003864:Depression, Chemical; D004920:Erythropoiesis / Q000187:drug effects; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D005492:Folic Acid / Q000494:pharmacology; D006098:Granulocytes / Q000166:cytology; D006410:Hematopoiesis / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D008264:Macrophages / Q000166:cytology; D051379:Mice; D011736:Pyridoxine / Q000494:pharmacology; D013154:Spleen / Q000187:drug effects
D000431:Ethanol; D005492:Folic Acid; D000079:Acetaldehyde; D011736:Pyridoxine