Cargando…
Establishment of a zebrafish hematological disease model induced by 1,4-benzoquinone
Benzene exposure is associated with various hematological disorders, in particular leukemia. The reactive metabolite of benzene, 1,4-benzoquinone (BQ), generated in bone marrow, is suggested to be a key molecule in mediating benzene-induced hematotoxicity and carcinogenicity. However, its pathogenic...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Company of Biologists Ltd
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6451425/ https://www.ncbi.nlm.nih.gov/pubmed/30898970 http://dx.doi.org/10.1242/dmm.037903 |
Sumario: | Benzene exposure is associated with various hematological disorders, in particular leukemia. The reactive metabolite of benzene, 1,4-benzoquinone (BQ), generated in bone marrow, is suggested to be a key molecule in mediating benzene-induced hematotoxicity and carcinogenicity. However, its pathogenic role remains largely unknown due to a lack of suitable vertebrate whole-organism models. Here, we present an in vivo study to reveal the effect of BQ exposure on hematotoxicity in zebrafish. From embryonic stages to adulthood, BQ exposure suppressed erythroid and lymphoid hematopoiesis but led to abnormal accumulation of myeloid cells and precursors, which resembles benzene-induced cytopenia and myeloid dysplasia in humans. This myeloid expansion is caused by granulocyte, but not macrophage, lineage, emphasizing the significant role of lineage specificity in BQ-mediated hematopoietic toxicity. Analysis of the c-myb (also known as myb)-deficient mutant cmyb(hkz3) revealed that BQ induced neutrophilia in a c-myb-dependent manner, demonstrating that c-myb is a key intrinsic mediator of BQ hematotoxicity. Our study reveals that BQ causes lineage-specific hematotoxicity in zebrafish from embryonic stages to adulthood. Since c-myb is indispensable for BQ to induce neutrophilia, c-myb could serve as a potential drug target for reversing BQ hematotoxicity. |
---|