Dietary NiCl₂ causes G₂/M cell cycle arrest in the broiler's kidney

Area of Science:

• Molecular Biology
• Cell Biology
• Toxicology

Background:

• Cell cycle regulation is crucial for normal cellular function and organism development.
• Environmental factors and chemical exposures can disrupt cell cycle progression, leading to adverse health outcomes.
• Nickel compounds are known environmental contaminants with potential toxicological effects.

Purpose of the Study:

• To investigate the effects of dietary nickel chloride (NiCl2) on cell cycle progression.
• To elucidate the molecular mechanisms underlying NiCl2-induced cell cycle alterations.
• To identify specific proteins and genes involved in the cellular response to NiCl2 exposure.

Main Methods:

• Administration of varying doses of NiCl2 in the diet.
• Analysis of cell cycle distribution using flow cytometry.
• Assessment of protein and mRNA expression levels of key cell cycle regulators (e.g., ATM, p53, Chk1/2, p21, cdc25C, cdc2, cyclinB, PCNA) via Western blotting and RT-qPCR.

Main Results:

• Dietary NiCl2 at concentrations exceeding 300 mg/kg induced a significant G2/M cell cycle arrest.
• A reduction in the proportion of cells in the S phase was observed.
• Upregulation of phosphorylated ataxia telangiectasia mutated (p-ATM), p53, p-Chk1, p-Chk2, p21 protein and mRNA expression was noted.
• Downregulation of p-cdc25C, cdc2, cyclinB, and proliferating cell nuclear antigen (PCNA) protein and mRNA expression was observed.

Conclusions:

• Dietary exposure to excess NiCl2 disrupts normal cell cycle progression, leading to G2/M arrest.
• The observed cell cycle arrest is mediated by the modulation of critical signaling pathways involving ATM, p53, and checkpoint kinases.
• NiCl2 exposure significantly alters the expression of proteins and genes essential for cell cycle progression and DNA repair.