Clastogenicity and Aneugenicity of 1,4-Benzoquinone in Different Lineages of Mouse Hematopoietic Stem/Progenitor Cells

Abstract

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 (p < 0.05) in MBMCs and all progenitors at all concentrations. As a comparison, Pre-B lymphoid progenitor demonstrated a significantly higher percentage of CA (p < 0.05) than erythroid progenitor at 1.25, 2.5, and 7 μM as well as a significantly higher percentage (p < 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.

Future stem cell analysis: progress and challenges towards state-of-the art approaches in automated cells analysis

“…A stem cell has self-renewal ability and differentiates into a new cell categorised into multipotent stem cells. The HSCs are responsible for the differentiation of the blood cells such as erythrocyte (red blood cell), leukocyte (white blood cell), and platelet cell lineages through the hematopoiesis process ( Wu et al, 1968 ; Chow et al, 2021 ). The hematopoiesis process has been practically demonstrated in nuclear survivors and irradiated mice bone marrow transplants.…”

Blocking exosomal secretion aggravated 1,4‐benzoquinone‐induced cytotoxicity

“…It is generally accepted that 1,4‐benzoquinone (PBQ), the active benzene metabolite, causes bone marrow toxicity and hematotoxicity via oxidative stress and genotoxicity mechanisms 11,12 . Numerous studies have revealed that PBQ increases reactive oxygen species (ROS) generation, decreases mitochondrial membrane potential (MMP), induces autophagy, and ultimately leads to cell apoptosis in vitro 13–16 …”