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 5μM for 24h. 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 2.5μM (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 5μM 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.