Chow Paik Wah, Abd Hamid Zariyantey, Mathialagan Ramya Dewi, Rajab Nor Fadilah, Shuib Salwati, Sulong Sarina
Biomedical Science Programme and Center for Diagnostic, Therapeutic and Investigative Studies, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Kuala Lumpur 50300, Malaysia.
Biomedical Science Programme and Center for Healthy Ageing & Wellness, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Kuala Lumpur 50300, Malaysia.
Toxics. 2021 May 12;9(5):107. doi: 10.3390/toxics9050107.
Previous reports on hematotoxicity and leukemogenicity related to benzene exposure highlighted its adverse effects on hematopoiesis. Despite the reported findings, studies concerning the mechanism of benzene affecting chromosomal integrity in lineage-committed hematopoietic stem/progenitor cells (HSPCs) remain unclear. Here, we studied the clastogenicity and aneugenicity of benzene in lineage-committed HSPCs via karyotyping. Isolated mouse bone marrow cells (MBMCs) were exposed to the benzene metabolite 1,4-benzoquinone (1,4-BQ) at 1.25, 2.5, 5, 7, and 12 μM for 24 h, followed by karyotyping. Then, the chromosomal aberration (CA) in 1,4-BQ-exposed hematopoietic progenitor cells (HPCs) comprising myeloid, Pre-B lymphoid, and erythroid lineages were evaluated following colony-forming cell (CFC) assay. Percentage of CA, predominantly via Robertsonian translocation (Rb), was increased significantly ( < 0.05) in MBMCs and all progenitors at all concentrations. As a comparison, Pre-B lymphoid progenitor demonstrated a significantly higher percentage of CA ( < 0.05) than erythroid progenitor at 1.25, 2.5, and 7 μM as well as a significantly higher percentage ( < 0.05) than myeloid progenitor at 7 μM of 1,4-BQ. In conclusion, 1,4-BQ induced CA, particularly via Rb in both MBMCs and HPCs, notably via a lineage-dependent response. The role of lineage specificity in governing the clastogenicity and aneugenicity of 1,4-BQ deserves further investigation.
先前关于苯暴露相关血液毒性和致白血病性的报告强调了其对造血作用的不良影响。尽管有这些报告结果,但关于苯影响定向造血干/祖细胞(HSPCs)染色体完整性机制的研究仍不清楚。在此,我们通过核型分析研究了苯在定向HSPCs中的致断裂性和非整倍体性。将分离的小鼠骨髓细胞(MBMCs)分别暴露于浓度为1.25、2.5、5、7和12 μM的苯代谢物1,4-苯醌(1,4-BQ)中24小时,随后进行核型分析。然后,在集落形成细胞(CFC)测定后,评估暴露于1,4-BQ的包括髓系、前B淋巴细胞系和红系的造血祖细胞(HPCs)中的染色体畸变(CA)。在所有浓度下,MBMCs和所有祖细胞中CA的百分比,主要通过罗伯逊易位(Rb)显著增加(<0.05)。作为比较,在1.25、2.5和7 μM的1,4-BQ浓度下,前B淋巴细胞系祖细胞的CA百分比显著高于红系祖细胞(<0.05),在7 μM的1,4-BQ浓度下,也显著高于髓系祖细胞(<0.05)。总之,1,4-BQ诱导了CA,特别是在MBMCs和HPCs中通过Rb诱导,尤其是通过一种谱系依赖性反应。谱系特异性在控制1,4-BQ的致断裂性和非整倍体性中的作用值得进一步研究。