氟对小鼠成釉细胞DNA损伤、细胞凋亡和增殖周期的影响
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摘要
目的探讨氟对小鼠成釉细胞DNA损伤、细胞凋亡和增殖周期的影响。方法取小鼠成釉细胞,分为0.25、0.50、1.00、2.00和4.00 mmol/L剂量组,经氟化钠染毒24 h后,收集细胞,检测细胞内超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)活力、脂质过氧化物丙二醛(MDA)和8-OHd G含量、DNA单链断裂情况、细胞凋亡、细胞增殖周期以及细胞增殖活性。结果小鼠成釉细胞在氟浓度为2.00和4.00 mmol/L下作用24 h后,细胞SOD、GSH-Px的活性降低(P<0.05),MDA含量升高(P<0.05)。1.00和4.00 mmol/L剂量组的小鼠成釉细胞DNA尾长、Olive尾距、尾DNA%、尾/头长比均明显高于对照组(P<0.05),且在此剂量条件下,小鼠成釉细胞8-OHd G的含量明显升高(P<0.05),而在2.00 mmol/L剂量条件下,小鼠成釉细胞DNA损伤各指标的变化不明显。在2.00 mmol/L剂量条件下,G0/G1和G2/M期细胞均显著增多,S期细胞较对照组明显减少(P<0.05)。在4.00 mmol/L浓度下,成釉细胞凋亡率明显升高,而细胞增殖活性则在0.25 mmol/L浓度就开始出现了明显的下降(P<0.05)。结论在一定剂量条件下,氟可引起小鼠成釉细胞氧化应激,DNA损伤,细胞凋亡,细胞增殖周期改变和细胞增殖活性的降低。氟在2.00 mmol/L剂量条件下可诱导小鼠成釉细胞抗氧化应激反应,但相关机制需结合Nrf2信号通路深入研究。
引文
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[18]陈嘉兴,陈智健,吴礼康,等.Nrf2信号因子在镉所致HEK细胞氧化损伤中的作用[J].华中科技大学学报(医学版),2017,46(2):145-149.
[2]范灵凯,梁俊,阳慧萍,等.有机氟生产工职业紧张状况及影响因素研究[J].实用预防医学,2017,24(8):897-901.
[3]钟苑芳,钟炜轲,陈秉,等.氟对大鼠成骨细胞氧化应激和8-羟基脱氧鸟苷生成影响[J].中国职业医学,2011,38(2):109-112.
[4]马林,张颖,钟鸣,等.氟对体外培养大鼠成釉细胞活性和细胞凋亡的影响[J].上海口腔医学,2014,23(5):519-523.
[5]Denbesten P,Li W.Chronic fluoride toxicity:dental fluorosis[J].Monogr Oral Sci,2011,22:81-95.
[6]李玲,刘怡,彭睿,等.氟对成釉细胞钙稳态的影响及其机制的研究进展[J].中国地方病防治杂志,2016,31(1):34-36.
[7]Suzuki M,Shin M,Simmer JP,et al.Fluoride affects enamel protein content via TGF-β1-mediated KLK4inhibition[J].J Dent Res,2014,93(10):1022-1027.
[8]Manivannan J,Sinha S,Ghosh M,et al.Evaluation of multi-end point assay to detect genotoxicity and oxidative stress in mice exposed to sodium fluoride[J].Mutat Res Genet Toxicol Environ Mutagen,2013,751(1):59-65.
[9]Thangapandiyan S,Miltonprabu S.Epigallocatechin gallate effectively ameliorates fluoride-induced oxidative stress and DNA damage in the liver of rats[J].Can J Physiol Pharmacol,2013,91(7):528-537.
[10]Campospereira FD,Lopesaguiar L,Renosto FL,et al.Genotoxic effect and rat hepatocyte death occurred after oxidative stress induction and antioxidant gene downregulation caused by long term fluoride exposure[J].Chem Biol Interact,2017,264:25-33.
[11]Dec K,Lukomska A,Maciejewska D,et al.The Influence of fluorine on the disturbances of homeostasis in the central nervous system[J].Biol Trace Elem Res,2016,177(2):224-234.
[12]吴礼康,陈嘉兴,田亚锋,等.DNA单链断裂与8-羟基脱氧鸟苷生成在镉所致人胚肾上皮细胞毒性作用分析[J].中国职业医学,2016,43(4):424-428.
[13]宋国华,高继萍,刘茂林,等.氟化钠诱导大鼠肾脏细胞DNA损伤及细胞凋亡的实验研究[J].毒理学杂志,2013,27(6):436-438.
[14]Li W,Jiang B,Cao X,et al.Protective effect of lycopene on fluoride-induced ameloblasts apoptosis and dental fluorosis through oxidative stress-mediated caspase pathways[J].Chem Biol Interact,2017,261:27-34.
[15]张颖,马林,李健,等.过量氟诱导成釉细胞钙超载及细胞凋亡的实验研究[J].华西口腔医学杂志,2014,32(6):542-546.
[16]Yan Q,Zhang YW,Denbesten P.Micromolar fluoride alters ameloblast lineage cells in vitro[J].J Dent Res,2007,86(4):336-340.
[17]钟苑芳,贺凌飞,余日安.转录因子NF-E2相关因子2-抗氧化转录元件信号通路组成与激活机制[J].中国职业医学,2010,37(5):416-419.
[18]陈嘉兴,陈智健,吴礼康,等.Nrf2信号因子在镉所致HEK细胞氧化损伤中的作用[J].华中科技大学学报(医学版),2017,46(2):145-149.