Elucidating Lineage-Specific Myelotoxicity and Chromosomal Abberation Status in Hydroquinone-Exposed Hematopoietic Stem / Progenitor Cells
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Keywords

benzene
hematopoietic stem
progenitor cells
hematotoxicity
myelotoxicity
lineage-dependent

How to Cite

Mohd Idris, J., Abdul Hamid, Z., Ng, K. E., Chow, P. W., Shuib, S., & Mathialagan, R. D. (2018). Elucidating Lineage-Specific Myelotoxicity and Chromosomal Abberation Status in Hydroquinone-Exposed Hematopoietic Stem / Progenitor Cells. Life Sciences, Medicine and Biomedicine, 2(1). https://doi.org/10.28916/lsmb.2.1.2018.10

Abstract

Benzene exposure has been associated with hematotoxicity and leukemogenicity. However, the impact of benzene exposure on complex microenvironment of Hematopoetic Stem Cells (HSCs) niche, comprising of HSCs and lineage-specific progenitors remains elusive. Thus, a study on benzene-targeting HSCs niche could uncover mechanism linking benzene to HSCs niche alteration. This study evaluates the lineage-specific responses following exposure to a benzene metabolite, namely hydroquinone (HQ) in targeting HSCs and myeloid-committed progenitors. Freshly isolated murine bone marrow cells (BMCs) were exposed to HQ at series of concentrations (0 – 50 µM) for 24 hours; followed by cell viability analysis using MTT assay. Chromosomal aberration (CA) status was determined using karyotyping analysis. Expression of surface antigen for HSCs (Sca-1) was confirmed by flow cytometer. Lineage-specific myelotoxicity was studied using the colony-forming unit (CFU) assay for the following myeloid progenitors: CFU granulocyte /erythrocyte /macrophage /megakaryocyte (CFU-GEMM), CFU-granulocyte/macrophage (CFU-GM), CFU-granulocyte (CFU-G), CFU-macrophage (CFU-M), CFU-erythroid (CFU-E) and Burst-forming unit erythroid (BFU-E). HQ reduced (p<0.05) viability of BMCs at 25 µM and 50 µM with the IC10, IC25, and IC50 were at 17 µM, 23 µM and 35 µM, respectively. Increased (p<0.05) frequency of CA was observed in HQ-treated group as compared to control. Reduced (p<0.05) Sca-1+ cells at 17 µM, 23 µM and 35 µM indicates cytotoxic effect of HQ targeting HSCs population. Reduced (p<0.05) total colony counts were noted following HQ exposure at 6.25 µM and a complete inhibition of colony growth were observed at higher concentration (12.5 µM). HQ reduced (p<0.05) the growth of CFU-GEMM, CFU-GM and CFU-G at 6.25 µM, while the growth of CFU-M, CFU-E and BFU-E were not remarkably affected at lower concentrations (1.56 µM and 6.25 µM). Conclusively, HQ induces chromosomal aberration and cytotoxicity on HSCs with notable lineage-specific responses in governing benzene-mediated myelotoxicity targeting HSCs niche.

https://doi.org/10.28916/lsmb.2.1.2018.10
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References

FRGS (UKM) FRGS/1/2016/SKK13/UKM/03/1