Research Papers: Immunology:

Sodium fluoride causes hepatocellular S-phase arrest by activating ATM-p53-p21 and ATR-Chk1-Cdc25A pathways in mice

Huan Liu, Qin Luo, Hengmin Cui _, Huidan Deng, Ping Kuang, Yujiao Lu, Jing Fang, Zhicai Zuo, Junliang Deng, Yinglun Li, Xun Wang and Ling Zhao

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Oncotarget. 2018; 9:4318-4337. https://doi.org/10.18632/oncotarget.23093

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Huan Liu1,*, Qin Luo1,*, Hengmin Cui1,2, Huidan Deng1, Ping Kuang1, Yujiao Lu1, Jing Fang1,2, Zhicai Zuo1,2, Junliang Deng1,2, Yinglun Li1,2, Xun Wang1,2 and Ling Zhao1,2

1 College of Veterinary Medicine, Sichuan Agricultural University, Wenjiang, Chengdu, China

2 Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Sichuan Agriculture University, Wenjiang, Chengdu, China

* These authors contributed equally to this work

Correspondence to:

Hengmin Cui, email:

Keywords: NaF; S phase arrest; protein expression; mRNA expression; liver; Immunology and Microbiology Section; Immune response; Immunity

Received: May 16, 2017 Accepted: November 14, 2017 Published: December 11, 2017


In this study, experimental pathology, flow cytometry (FCM), quantitative real-time polymerase chain reaction (qRT-PCR), and western blot (WB) were used to evaluate the effects of sodium fluoride (NaF) on hepatocellular cell cycle progression in mice. A total of 240 ICR mice were divided equally into four groups; the experimental groups received 12, 24, or 48 mg/kg NaF intragastrically for 42 days, while the control group received distilled water. Doses of NaF above 12 mg/kg increased the percentage of cells in S phase (S-phase arrest), reduced percentages of cells in G0/G1 or G2/M phase, and activated the ATM-p53-p21 and ATR-Chk1-Cdc25A pathways. Activation of these pathways was characterized by up-regulation of ATM, p53, p21, ATR, and Chk1 mRNA and protein expression, and down-regulation of Cdc25A, cyclin E, cyclin A, CDK2, CDK4, and proliferating cell nuclear antigen (PCNA) mRNA and protein expression. These results indicate that NaF caused S-phase arrest by activating the ATM-p53-p21 and ATR-Chk1-Cdc25A pathways.

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