Formaldehyde-induced hematopoietic stem and progenitor cell toxicity in mouse lung and nose
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GENOTOXICITY AND CARCINOGENICITY
Formaldehyde‑induced hematopoietic stem and progenitor cell toxicity in mouse lung and nose Yun Zhao1,2 · Laura C. Magaña1 · Haiyan Cui2 · Jiawei Huang2 · Cliona M. McHale1 · Xu Yang2 · Mark R. Looney3,4 · Rui Li2 · Luoping Zhang1 Received: 3 August 2020 / Accepted: 8 October 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Formaldehyde (FA), an economically important and ubiquitous chemical, has been classified as a human carcinogen and myeloid leukemogen. However, the underlying mechanisms of leukemogenesis remain unclear. Unlike many classical leukemogens that damage hematopoietic stem/progenitor cells (HSC/HPC) directly in the bone marrow, FA—as the smallest, most reactive aldehyde—is thought to be incapable of reaching the bone marrow through inhalation exposure. A recent breakthrough study discovered that mouse lung contains functional HSC/HPC that can produce blood cells and travel bidirectionally between the lung and bone marrow, while another early study reported the presence of HSC/HPC in rat nose. Based on these findings, we hypothesized that FA inhalation could induce toxicity in HSC/HPC present in mouse lung and/ or nose rather than in the bone marrow. To test this hypothesis, we adapted a commercially available protocol for culturing burst-forming unit-erythroid (BFU-E) and colony-forming unit-granulocyte, macrophage (CFU-GM) colonies from bone marrow and spleen to also enable culture of these colonies from mouse lung and nose, a novel application of this assay. We reported that in vivo exposure to FA at 3 mg/m3 or ex vivo exposure up to 400 µM FA decreased the formation of both colony types from mouse lung and nose as well as from bone marrow and spleen. These findings, to the best of our knowledge, are the first empirically to show that FA exposure can damage mouse pulmonary and olfactory HSC/HPC and provide potential biological plausibility for the induction of leukemia at the sites of entry rather than the bone marrow. Keywords Formaldehyde · Leukemogenesis · HSC/HPC · Colony · Toxicity
Introduction Yun Zhao and Laura C. Magaña contributed equally to this work. * Rui Li [email protected] * Luoping Zhang [email protected] 1
Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, CA, USA
2
Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan, China
3
Department of Medicine, University of California, San Francisco (UCSF), San Francisco, CA, USA
4
Department of Laboratory Medicine, University of California, San Francisco (UCSF), San Francisco, CA, USA
Formaldehyde (FA) is a ubiquitous chemical extensively used in various industries (Tang et al. 2009; Duong et al. 2011). Exposure to FA mainly occurs via inhalation or skin absorption in workers in certain occupational settings including the production of FA resins and textiles, as well as embalming and medical laboratories (Zhang et al. 2009
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