DNA damage, apoptosis and cell cycle changes induced by fluoride in rat oral mucosal cells and hepatocytes
DNA damage, apoptosis and cell cycle changes induced by fluoride in rat oral mucosal cells and hepatocytes
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DOI：
10.3748/wjg.v12.i7.1144
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发表时间：
2006-02-21
影响因子：
4.3
通讯作者：
Jian-Gang Chen
中科院分区：
文献类型：
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作者：
Ling-Fei He;Jian-Gang Chen
目的：研究氟对大鼠口腔黏膜细胞和肝细胞氧化应激、DNA损伤和细胞周期的影响。方法：雄性SD大鼠10只，体重80120 g，随机分为对照组和氟化组，每组5只。氟化组动物可自由饮用含150 mg/L氟化钠的去离子水。对照组给予蒸馏水。四周后，这些动物被杀。用Fenton法测定口腔粘膜和肝脏中的ROS，用硫代巴比妥酸(TBA)法测定脂质过氧化产物丙二醛(MDA)，用二硫代硝基苯甲酸(DTNB)法测定还原型谷胱甘肽(GSH)。用单细胞凝胶(SCG)电泳法或彗星试验检测口腔粘膜细胞和肝细胞的DNA损伤。结果：染氟组大鼠口腔粘膜和肝组织中ROS、MDA含量显著高于对照组(P<0.01)，而GSH含量显著低于对照组(P<0.01)。口腔粘膜中ROS、丙二醛和谷胱甘肽含量分别为(134.73+/-12.63)U/mg蛋白质、(1.48+/-0.13)mmol/mg蛋白质和(76.38+/-6.71)mmol/mg蛋白质；肝组织中分别为(143.45+/-11.76)U/mg蛋白质、(1.44+/-0.12)mmol/mg蛋白质和(78.83+/-7.72)mmol/mg蛋白质。染氟组口腔粘膜细胞DNA损伤率为50.20%，肝细胞DNA损伤率为44.80%，明显高于对照组(P<0.01)。染氟组口腔粘膜细胞凋亡率为(13.63+/-1.81)%，肝细胞凋亡率为(12.76+/-1.67)%，均高于对照组。过量氟可不同程度地降低处于G0/G1期和S G2/M期的口腔粘膜细胞和肝细胞的数量(P<；0.05)。结论：过量氟可引起大鼠口腔粘膜细胞和肝细胞的氧化应激和DNA损伤，并导致细胞凋亡和细胞周期的改变。(C)2006年WJG出版社。版权所有。
AIM: To study the effect of fluoride on oxidative stress, DNA damage and apoptosis as well as cell cycle of rat oral mucosal cells and hepatocytes.METHODS: Ten male SD rats weighing 80120 g were randomly divided into control group and fluoride group, 5 animals each group. The animals in fluoride group had free access to deionized water containing 150 mg/L sodium fluoride (NaF). The animals in control group were given distilled water. Four weeks later, the animals were killed. Reactive oxygen species (ROS) in oral mucosa and liver were measured by Fenton reaction, lipid peroxidation product, malondialdehyde (MDA), was detected by thiobarbituric acid (TBA) reaction, reduced glutathione (GSH) was assayed by dithionitrobenzoic acid (DTNB) reaction. DNA damage in oral mucosal cells and hepatocytes was determined by single cell gel (SCG) electrophoresis or comet assay. Apoptosis and cell cycle in oral mucosal cells and hepatocytes were detected by flow cytometry.RESULTS: The contents of ROS and MDA in oral mucosa and liver tissue of fluoride group were significantly higher than those of control group (P < 0.01), but the level of GSH was markedly decreased (P < 0.01). The contents of ROS, MDA and GSH were (134.73 +/- 12.63) U/mg protein, (1.48 +/- 0.13) mmol/mg protein and (76.38 +/- 6.71) mmol/mg protein in oral mucosa respectively, and (143.45 +/- 11.76) U/mg protein, (1.44 +/- 0.12) mmol/mg protein and (78.83 +/- 7.72) mmol/mg protein in liver tissue respectively. The DNA damage rate in fluoride group was 50.20% in oral mucosal cells and 44.80% in hepatocytes, higher than those in the control group (P < 0.01). The apoptosis rate in oral mucosal cells was (13.63 +/- 1.81) % in fluoride group, and (12.76 +/- 1.67) % in hepatocytes, higher than those in control group. Excess fluoride could differently lower the number of oral mucosal cells and hepatocytes at G0/G1 and S G2/M phases (P < 0.05).CONCLUSION: Excess fluoride can induce oxidativestress and DNA damage and lead to apoptosis and cell cycle change in rat oral mucosal cells and hepatocytes. (C) 2006 The WJG Press. All rights reserved.