title: Formaldehyde induces micronuclei in mouse erythropoietic cells and suppresses the expansion of human erythroid progenitor cells.
abstract: Although formaldehyde (FA) has been classified as a human leukemogen, the mechanisms of leukemogenesis remain elusive. Previously, using colony-forming assays in semi-solid media, we showed that FA exposure in vivo and in vitro was toxic to human hematopoietic stem/progenitor cells. In the present study, we have applied new liquid in vitro erythroid expansion systems to further investigate the toxic effects of FA (0-150 μM) on cultured mouse and human hematopoietic stem/progenitor cells. We determined micronucleus (MN) levels in polychromatic erythrocytes (PCEs) differentiated from mouse bone marrow. We measured cell growth, cell cycle distribution, and chromosomal instability, in erythroid progenitor cells (EPCs) expanded from human peripheral blood mononuclear cells. FA significantly induced MN in mouse PCEs and suppressed human EPC expansion in a dose-dependent manner, compared with untreated controls. In the expanded human EPCs, FA slightly increased the proportion of cells in G2/M at 100 μM and aneuploidy frequency in chromosomes 7 and 8 at 50 μM. Our findings provide further evidence of the toxicity of FA to hematopoietic stem/progenitor cells and support the biological plausibility of FA-induced leukemogenesis.
authors.affiliation: Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, CA 94720, USA.
authors.forename: Zhiying
authors.initials: Z
authors.lastname: Ji
authors.forename: Xiyi
authors.initials: X
authors.lastname: Li
authors.forename: Michele
authors.initials: M
authors.lastname: Fromowitz
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Mutter-Rottmayer
authors.forename: Judy
authors.initials: J
authors.lastname: Tung
authors.forename: Martyn T
authors.initials: MT
authors.lastname: Smith
authors.forename: Luoping
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D004305:Dose-Response Relationship, Drug; D015672:Erythroid Precursor Cells / Q000166:cytology / Q000187:drug effects*; D005557:Formaldehyde / Q000633:toxicity*; D006801:Humans; D051379:Mice; D048629:Micronuclei, Chromosome-Defective
chemical_list: D005557:Formaldehyde
keywords: Aneuploidy; Erythroid progenitor; Formaldehyde; Micronuclei