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The findings of this study indicate that NAC supplementation may potentially overcome the therapeutic limitations of -maintained HSPCs.

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.

Summary:We have used a superparamagnetic microbead selection system to positively select a murine bone marrow CD8 + cell population. The functional ability of these cells to enhance allogeneic bone marrow engraftment was compared with that of fluorescence activated cell sorter purified CD8 ؉ cells. The CD8 ؉ cell population prepared by the microbead selection procedure was as effective as cell sorter purified CD8 ؉ cells in enhancing T celldepleted allogeneic bone marrow engraftment in lethally irradiated mice. Phenotypic characterization of these cells shows that most of these CD8 ؉ cells express CD3 and the T cell antigen receptor complex.

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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 lineagespecific 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.

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