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

Huan Liu1, Qin Luo1, Hengmin Cui1,2

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

Oncotarget
|February 14, 2018
PubMed

Insights

Sodium fluoride (NaF) exposure in mice disrupts liver cell cycles, causing S-phase arrest. This occurs through the activation of specific molecular pathways, impacting cell division and proliferation.

Area of Science:

  • Hepatocellular toxicology
  • Cell cycle regulation
  • Molecular pathology

Background:

  • Hepatocellular cell cycle progression is crucial for liver function.
  • Environmental toxins can disrupt normal cellular processes.
  • Sodium fluoride (NaF) is a common environmental contaminant with potential health effects.

Purpose of the Study:

  • To investigate the impact of sodium fluoride (NaF) on hepatocellular cell cycle progression in mice.
  • To elucidate the molecular mechanisms underlying NaF-induced cell cycle alterations.

Main Methods:

  • Experimental pathology, flow cytometry (FCM), quantitative real-time polymerase chain reaction (qRT-PCR), and western blot (WB) were employed.
  • 240 ICR mice were administered varying doses of NaF (12, 24, 48 mg/kg) or distilled water for 42 days.
  • Analysis focused on cell cycle phase distribution and key pathway protein/mRNA expression.

Main Results:

  • NaF doses exceeding 12 mg/kg induced S-phase arrest in liver cells.
  • NaF exposure reduced the proportion of cells in G0/G1 and G2/M phases.
  • The ATM-p53-p21 and ATR-Chk1-Cdc25A signaling pathways were activated, with altered expression of related proteins and mRNA.

Conclusions:

  • Sodium fluoride exposure causes hepatocellular S-phase arrest in mice.
  • NaF-induced cell cycle disruption is mediated by the activation of ATM-p53-p21 and ATR-Chk1-Cdc25A pathways.
  • These findings highlight the potential hepatotoxicity of NaF through cell cycle interference.
Keywords:
Immune responseImmunityImmunology and Microbiology SectionNaFS phase arrestlivermRNA expressionprotein expression

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