Differential responses of lineages-committed hematopoietic progenitors and altered expression of self-renewal and differentiation-related genes in 1,4-benzoquinone (1,4-BQ) exposure

Research output: Research - peer-reviewArticle

Abstract

Despite of reports on hematotoxic and leukemogenic evidences related to benzene exposure, the mechanism of benzene toxicity affecting the hematopoietic stem and progenitor cells (HSPCs) fate remains unclear. This study aims to elucidate the benzene's effect on the lineages-committed progenitors and genes-regulating self-renewal and differentiation of HSPCs. Isolated mouse bone marrow (BM) cells were exposed to the benzene metabolite, 1,4-benzoquinone (1,4-BQ) at 1.25, 2.5, and 5 μM for 24 h. The clonogenic potency of erythroid, myeloid, and Pre-B lymphoid progenitors was evaluated through colony-forming-cell assay. Quantitative real time-PCR was used to analyze the self-renewal (Bmi-1, HoxB4, and Wnt3) and differentiation (GATA1, GATA2, and GATA3)-related genes’ expression levels. 1,4-BQ exposure significantly lowered the clonogenicity of the myeloid progenitor at 1.25 and 2.5 μM (p < 0.05), but affected neither the erythroid nor Pre-B lymphoid progenitors. Furthermore, significant upregulation of HoxB4 expression level was observed at all concentrations. GATA3 and Bmi-1 expressions were also significant upregulated at 2.5 and 5 μM 1,4-BQ, respectively. In conclusion, 1,4-BQ could modulate the fate of HSPCs by altering the self-renewal and differentiation related genes. The definite role of lineages specificity and responsive genes in governing the hematotoxicity and leukemogenicity of 1,4-BQ should be further investigated.

LanguageEnglish
Pages122-128
Number of pages7
JournalToxicology in Vitro
Volume46
DOIs
StatePublished - 1 Feb 2018

Fingerprint

Hematopoietic Stem Cells
Genes
benzoquinone
Benzene
Metabolites
Gene expression
Toxicity
Assays
Bone
Cells
Bone Marrow Cells
Real-Time Polymerase Chain Reaction
Up-Regulation
Gene Expression
Cell Self Renewal

Keywords

  • 1,4-benzoquinone
  • Benzene
  • Differentiation
  • Hematopoietic stem and progenitor cells
  • Lineages
  • Self-renewal

ASJC Scopus subject areas

  • Toxicology

Cite this

@article{f27d4e57d8e349caa0fe27da00daa0cc,
title = "Differential responses of lineages-committed hematopoietic progenitors and altered expression of self-renewal and differentiation-related genes in 1,4-benzoquinone (1,4-BQ) exposure",
abstract = "Despite of reports on hematotoxic and leukemogenic evidences related to benzene exposure, the mechanism of benzene toxicity affecting the hematopoietic stem and progenitor cells (HSPCs) fate remains unclear. This study aims to elucidate the benzene's effect on the lineages-committed progenitors and genes-regulating self-renewal and differentiation of HSPCs. Isolated mouse bone marrow (BM) cells were exposed to the benzene metabolite, 1,4-benzoquinone (1,4-BQ) at 1.25, 2.5, and 5 μM for 24 h. The clonogenic potency of erythroid, myeloid, and Pre-B lymphoid progenitors was evaluated through colony-forming-cell assay. Quantitative real time-PCR was used to analyze the self-renewal (Bmi-1, HoxB4, and Wnt3) and differentiation (GATA1, GATA2, and GATA3)-related genes’ expression levels. 1,4-BQ exposure significantly lowered the clonogenicity of the myeloid progenitor at 1.25 and 2.5 μM (p < 0.05), but affected neither the erythroid nor Pre-B lymphoid progenitors. Furthermore, significant upregulation of HoxB4 expression level was observed at all concentrations. GATA3 and Bmi-1 expressions were also significant upregulated at 2.5 and 5 μM 1,4-BQ, respectively. In conclusion, 1,4-BQ could modulate the fate of HSPCs by altering the self-renewal and differentiation related genes. The definite role of lineages specificity and responsive genes in governing the hematotoxicity and leukemogenicity of 1,4-BQ should be further investigated.",
keywords = "1,4-benzoquinone, Benzene, Differentiation, Hematopoietic stem and progenitor cells, Lineages, Self-renewal",
author = "Chow, {Paik Wah} and Rajab, {Nor Fadilah} and Chua, {Kien Hui} and Chan, {Kok Meng} and {Abd Hamid}, Zariyantey",
year = "2018",
month = "2",
doi = "10.1016/j.tiv.2017.10.001",
volume = "46",
pages = "122--128",
journal = "Toxicology in Vitro",
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publisher = "Elsevier Limited",

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T1 - Differential responses of lineages-committed hematopoietic progenitors and altered expression of self-renewal and differentiation-related genes in 1,4-benzoquinone (1,4-BQ) exposure

AU - Chow,Paik Wah

AU - Rajab,Nor Fadilah

AU - Chua,Kien Hui

AU - Chan,Kok Meng

AU - Abd Hamid,Zariyantey

PY - 2018/2/1

Y1 - 2018/2/1

N2 - Despite of reports on hematotoxic and leukemogenic evidences related to benzene exposure, the mechanism of benzene toxicity affecting the hematopoietic stem and progenitor cells (HSPCs) fate remains unclear. This study aims to elucidate the benzene's effect on the lineages-committed progenitors and genes-regulating self-renewal and differentiation of HSPCs. Isolated mouse bone marrow (BM) cells were exposed to the benzene metabolite, 1,4-benzoquinone (1,4-BQ) at 1.25, 2.5, and 5 μM for 24 h. The clonogenic potency of erythroid, myeloid, and Pre-B lymphoid progenitors was evaluated through colony-forming-cell assay. Quantitative real time-PCR was used to analyze the self-renewal (Bmi-1, HoxB4, and Wnt3) and differentiation (GATA1, GATA2, and GATA3)-related genes’ expression levels. 1,4-BQ exposure significantly lowered the clonogenicity of the myeloid progenitor at 1.25 and 2.5 μM (p < 0.05), but affected neither the erythroid nor Pre-B lymphoid progenitors. Furthermore, significant upregulation of HoxB4 expression level was observed at all concentrations. GATA3 and Bmi-1 expressions were also significant upregulated at 2.5 and 5 μM 1,4-BQ, respectively. In conclusion, 1,4-BQ could modulate the fate of HSPCs by altering the self-renewal and differentiation related genes. The definite role of lineages specificity and responsive genes in governing the hematotoxicity and leukemogenicity of 1,4-BQ should be further investigated.

AB - Despite of reports on hematotoxic and leukemogenic evidences related to benzene exposure, the mechanism of benzene toxicity affecting the hematopoietic stem and progenitor cells (HSPCs) fate remains unclear. This study aims to elucidate the benzene's effect on the lineages-committed progenitors and genes-regulating self-renewal and differentiation of HSPCs. Isolated mouse bone marrow (BM) cells were exposed to the benzene metabolite, 1,4-benzoquinone (1,4-BQ) at 1.25, 2.5, and 5 μM for 24 h. The clonogenic potency of erythroid, myeloid, and Pre-B lymphoid progenitors was evaluated through colony-forming-cell assay. Quantitative real time-PCR was used to analyze the self-renewal (Bmi-1, HoxB4, and Wnt3) and differentiation (GATA1, GATA2, and GATA3)-related genes’ expression levels. 1,4-BQ exposure significantly lowered the clonogenicity of the myeloid progenitor at 1.25 and 2.5 μM (p < 0.05), but affected neither the erythroid nor Pre-B lymphoid progenitors. Furthermore, significant upregulation of HoxB4 expression level was observed at all concentrations. GATA3 and Bmi-1 expressions were also significant upregulated at 2.5 and 5 μM 1,4-BQ, respectively. In conclusion, 1,4-BQ could modulate the fate of HSPCs by altering the self-renewal and differentiation related genes. The definite role of lineages specificity and responsive genes in governing the hematotoxicity and leukemogenicity of 1,4-BQ should be further investigated.

KW - 1,4-benzoquinone

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KW - Hematopoietic stem and progenitor cells

KW - Lineages

KW - Self-renewal

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DO - 10.1016/j.tiv.2017.10.001

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SP - 122

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JO - Toxicology in Vitro

T2 - Toxicology in Vitro

JF - Toxicology in Vitro

SN - 0887-2333

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