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

Sun R, Zhang J, Xiong M, Wei H, Tan K, Yin L, Pu Y - Int J Environ Res Public Health (2015)

Bottom Line: 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 Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Environmental Medicine Engineering, Ministry of Education. sunrongli20609@163.com.

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.

No MeSH data available.


Related in: MedlinePlus

β-catenin, c-Myc, Notch1, cyclin D1, Bmi 1 and p53 gene expression in mouse LSK cells following 10 months post-benzene exposure.
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ijerph-12-09298-f005: β-catenin, c-Myc, Notch1, cyclin D1, Bmi 1 and p53 gene expression in mouse LSK cells following 10 months post-benzene exposure.

Mentions: The nest real-time PCR was used to detect expression of 6 genes in Wnt/β-catenin, Notch and Hh signaling pathways. In this study, the mRNA level of β-catenin in LSKs was found declined slightly in B1 group and elevated in B2 group without significant differences (Figure 5).The specific known target genes of Wnt signaling include c-myc and cyclin D1. The expression of c-myc was decreased only in B1 group and no significant difference was found in B2 group. Elevated levels of cyclin D1 were detected in benzene groups with benzene dose increased, but the difference was not statistically significant because of variability between mice. Our results showed that the mRNA level of Notch1 was decreased in mice exposed to benzene. For the Bmi 1 mRNA expression, no statistical difference was found between these three groups. The mRNA level of p53, which is one of the target genes of Bmi 1, was lower than that of the non-exposure controls.


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

Sun R, Zhang J, Xiong M, Wei H, Tan K, Yin L, Pu Y - Int J Environ Res Public Health (2015)

β-catenin, c-Myc, Notch1, cyclin D1, Bmi 1 and p53 gene expression in mouse LSK cells following 10 months post-benzene exposure.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4555281&req=5

ijerph-12-09298-f005: β-catenin, c-Myc, Notch1, cyclin D1, Bmi 1 and p53 gene expression in mouse LSK cells following 10 months post-benzene exposure.
Mentions: The nest real-time PCR was used to detect expression of 6 genes in Wnt/β-catenin, Notch and Hh signaling pathways. In this study, the mRNA level of β-catenin in LSKs was found declined slightly in B1 group and elevated in B2 group without significant differences (Figure 5).The specific known target genes of Wnt signaling include c-myc and cyclin D1. The expression of c-myc was decreased only in B1 group and no significant difference was found in B2 group. Elevated levels of cyclin D1 were detected in benzene groups with benzene dose increased, but the difference was not statistically significant because of variability between mice. Our results showed that the mRNA level of Notch1 was decreased in mice exposed to benzene. For the Bmi 1 mRNA expression, no statistical difference was found between these three groups. The mRNA level of p53, which is one of the target genes of Bmi 1, was lower than that of the non-exposure controls.

Bottom Line: 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 Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Environmental Medicine Engineering, Ministry of Education. sunrongli20609@163.com.

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.

No MeSH data available.


Related in: MedlinePlus