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Int. J. Environ. Res. Public Health 2015, 12(8), 9298-9313; doi:10.3390/ijerph120809298

Altered Expression of Genes in Signaling Pathways Regulating Proliferation of Hematopoietic Stem and Progenitor Cells in Mice with Subchronic Benzene Exposure

Key Laboratory of Environmental Medicine Engineering, Ministry of Education
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Author to whom correspondence should be addressed.
Academic Editor: Paul B. Tchounwou
Received: 14 June 2015 / Revised: 29 July 2015 / Accepted: 2 August 2015 / Published: 7 August 2015
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Abstract

Leukemias and hematopoietic disorders induced by benzene may arise from the toxicity of benzene to hematopoietic stem or progenitor cells (HS/PCs). Since there is a latency period between initial benzene exposure and the development of leukemia, subsequent impact of benzene on HS/PCs are crucial for a deeper understanding of the carcinogenicity and hematotoxicity in post-exposure stage. This study aims to explore the effects of benzene on HS/PCs and gene-expression in Wnt, Notch and Hh signaling pathways in post-exposure stage. The C3H/He mice were injected subcutaneously with benzene (0, 150, 300 mg/kg/day) for three months and were monitored for another 10 months post-exposure. The body weights were monitored, the relative organ weights, blood parameters and bone marrow smears were examined. Frequency of lineage- sca-1+ c-kit+ (LSK) cells, capability of colony forming and expression of genes in Wnt, Notch and Hedghog (Hh) signaling pathways were also analyzed. The colony formation of the progenitor cells for BFU-E, CFU-GEMM and CFU-GM was significantly decreased with increasing benzene exposure relative to controls, while no significant difference was observed in colonies for CFU-G and CFU-M. The mRNA level of cyclin D1 was increased and Notch 1 and p53 were decreased in LSK cells in mice exposed to benzene but with no statistical significance. These results suggest that subsequent toxic effects of benzene on LSK cells and gene expression in Wnt, Notch and Hh signaling pathways persist in post-exposure stage and may play roles in benzene-induced hematotoxicity. View Full-Text
Keywords: benzene; post-exposure toxicity; hematopoietic stem cell; Wnt; Notch; Hedghog benzene; post-exposure toxicity; hematopoietic stem cell; Wnt; Notch; Hedghog
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Sun, R.; Zhang, J.; Xiong, M.; Wei, H.; Tan, K.; Yin, L.; Pu, Y. Altered Expression of Genes in Signaling Pathways Regulating Proliferation of Hematopoietic Stem and Progenitor Cells in Mice with Subchronic Benzene Exposure. Int. J. Environ. Res. Public Health 2015, 12, 9298-9313.

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Int. J. Environ. Res. Public Health EISSN 1660-4601 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
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