Limits...
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

Colony-forming capability of mice after 10 months post-benzene exposure. * p < 0.05 compared with control.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4555281&req=5

ijerph-12-09298-f004: Colony-forming capability of mice after 10 months post-benzene exposure. * p < 0.05 compared with control.

Mentions: The frequency of LSK cells was dramatically decreased in Benzene groups after 3 months of benzene exposure. While at 10 months post benzene exposure, the frequency of LSK cells in the BM was slightly increased in Benzene groups although no statistical difference was noted as compared to Control group (Figure 3). To assess progenitor function, we performed colony forming cells assay, enumerating both erythroid burst-forming unit (BFU-E) as well as the committed progenitors granulocytes-erythroid-monocyte-megakaryocyte (GEMM), granulocyte-macrophages (GM), granulocytes (G), and macrophages (M) (Figure 4). By 10 months post-benzene exposure, the BM cells were harvested and plated in cytokine-supplemented methylcellulose. Twelve days later, the G and M progenitors were decreased but no significant differences compared with control, whereas BFU-E, CFU-GEMM and CFU-GM progenitors showed significantly dose-dependent decline in the benzene groups. Although no significant changes were found in percentage of HSC cells, the colony formation ability of progenitors was dramatically declined even after all benzene exposure has been stopped for ten months.


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)

Colony-forming capability of mice after 10 months post-benzene exposure. * p < 0.05 compared with control.
© Copyright Policy
Related In: Results  -  Collection

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

ijerph-12-09298-f004: Colony-forming capability of mice after 10 months post-benzene exposure. * p < 0.05 compared with control.
Mentions: The frequency of LSK cells was dramatically decreased in Benzene groups after 3 months of benzene exposure. While at 10 months post benzene exposure, the frequency of LSK cells in the BM was slightly increased in Benzene groups although no statistical difference was noted as compared to Control group (Figure 3). To assess progenitor function, we performed colony forming cells assay, enumerating both erythroid burst-forming unit (BFU-E) as well as the committed progenitors granulocytes-erythroid-monocyte-megakaryocyte (GEMM), granulocyte-macrophages (GM), granulocytes (G), and macrophages (M) (Figure 4). By 10 months post-benzene exposure, the BM cells were harvested and plated in cytokine-supplemented methylcellulose. Twelve days later, the G and M progenitors were decreased but no significant differences compared with control, whereas BFU-E, CFU-GEMM and CFU-GM progenitors showed significantly dose-dependent decline in the benzene groups. Although no significant changes were found in percentage of HSC cells, the colony formation ability of progenitors was dramatically declined even after all benzene exposure has been stopped for ten months.

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