| 1 - 硝基芘对GC - 2细胞的损伤效应及AhR信号通路的活化 |
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| 引用本文： | 邓久洋1,崔浩楠2,杨望2,柴子力2,史富全2,凌曦2,牛侨1,敖琳2,曹佳1,2. 1 - 硝基芘对GC - 2细胞的损伤效应及AhR信号通路的活化[J]. 现代预防医学, 2022, 0(10): 1874-1880 |
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| 作者姓名： | 邓久洋1 崔浩楠2 杨望2 柴子力2 史富全2 凌曦2 牛侨1 敖琳2 曹佳1 2 |
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| 作者单位： | 1.山西医科大学公共卫生学院劳动卫生教研室,山西 太原 030001;2.陆军军医大学军事预防医学系军事毒理学教研室,重庆 400038 |
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| 摘 要： | 目的 研究1 - 硝基芘（1 - nitropyrene, 1 - NP）对小鼠精母细胞株GC - 2的损伤效应及芳香烃受体（aryl hydrocarbon receptor, AhR）信号通路的影响。方法 建立不同剂量1 - NP染毒的GC - 2细胞模型,采用CCK - 8法检测细胞活性,流式细胞术检测细胞周期,Western blot分析各组细胞DNA双链断裂损伤标志物γ - H2AX、DNA损伤反应通路蛋白以及AhR通路蛋白的表达。实时荧光定量PCR检测细胞色素450 (CYP)1a1和1b1 mRNA表达水平。结果 1 - NP处理可导致GC - 2细胞活性降低及G2/M期细胞比例升高,同时诱导γ - H2AX蛋白表达升高,DNA损伤反应及细胞周期G2/M期检测点蛋白ATM、Chk1、Cdc25c、Cdc2的磷酸化表达水平升高,Cyclin B1表达降低。1 - NP染毒也提高了GC - 2细胞中AhR核蛋白及下游靶基因CYP1A1的蛋白表达,提高了Cyp1a1和Cyp1b1的转录表达水平。结论 1 - NP暴露造成小鼠生精细胞的DNA损伤、细胞周期阻滞和细胞活性抑制,其效应可能与AhR信号通路的活化及对化学物的代谢活化有关。
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| 关 键 词： | 1 - 硝基芘 生精细胞 DNA损伤 芳香烃受体 |
Adverse effects of 1-nitropyrene on GC-2 cells and the activation of aryl hydrocarbon receptor signaling pathway |
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| DENG Jiu-yang,CUI Hao-nan,YANG Wang,CHAI Zi-li,SHI Fu-quan,LING Xi,NIU Qiao,AO Lin,CAO Jia. Adverse effects of 1-nitropyrene on GC-2 cells and the activation of aryl hydrocarbon receptor signaling pathway[J]. Modern Preventive Medicine, 2022, 0(10): 1874-1880 |
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| Authors: | DENG Jiu-yang CUI Hao-nan YANG Wang CHAI Zi-li SHI Fu-quan LING Xi NIU Qiao AO Lin CAO Jia |
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| Affiliation: | *Department of Labor Health, School of Public Health, Shanxi Medical University, Taiyuan, Shanxi 030001, China |
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| Abstract: | Objective To investigate the effects of 1-nitropyrene (1-NP) on the damage of mouse spermatocyte cell line GC-2 and the effect of aryl hydrocarbon receptor (AhR) signaling pathway. Methods GC-2 cells were exposed to different doses of 1-NP. Cell viability was detected by CCK-8 method, cell cycle progression was detected by flow cytometry, and expression of DNA double-strand breaks marker γ-H2AX, proteins associated with DNA damage response pathway and AhR pathway was analyzed by Western blot. The mRNA expression levels of cytochrome 450 (CYP) 1a1 and 1b1 were detected by real-time fluorescence quantitative PCR. Results 1-NP treatment decreased the viability of GC-2 cells and increased the proportion of cells in G2/M phase. We also observed significantly increased levels of γ-H2AX, phosphorylated proteins associated with DNA damage response pathway, including ATM, Chk1, Cdc25c and Cdc2, and decreased level of Cyclin B1 expression in cells exposed to 1-NP. Additionally, 1-NP increased the nuclear expression level of AhR protein and its downstream protein of CYP1A1 in GC-2 cells. Increased transcriptional expression of Cyp1a1 and Cyp1b1was also found in 1-NP-exposed cells. Conclusion Exposure of 1-NP could induce DNA damage, cell cycle arrest and cell viability inhibition in mouse spermatogenic cells, which may be related to the metabolic activation of chemicals through AhR signaling pathway. |
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| Keywords: | 1-nitropyrene Spermatogenic cell DNA damage Aryl hydrocarbon receptor |
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