The molecular mechanism of G2M cell cycle arrest induced by AFB1 in the jejunum

Oncotarget. 2016 Jun 14;7(24):35592-35606. doi: 10.18632/oncotarget.9594.

Abstract

Aflatoxin B1 (AFB1) has potent hepatotoxic, carcinogenic, genotoxic, immunotoxic and other adverse effects in human and animals. The aim of this study was to investigate the molecular mechanism of G2/M cell cycle arrest induced by AFB1 in the jejunum of broilers. Broilers, as experimental animals, were fed 0.6 mg/kg AFB1 diet for 3 weeks. Our results showed that AFB1 reduced the jejunal villus height, villus height/crypt ratio and caused G2/M cell cycle arrest. The G2/M cell cycle was accompanied by the increase of ataxia telangiectasia mutated (ATM), p53, Chk2, p21 protein and mRNA expression, and the decrease of Mdm2, cdc25C, cdc2, cyclin B and proliferating cell nuclear antigen protein and mRNA expression. In conclusion, AFB1 blocked G2/M cell cycle by ATM pathway in the jejunum of broilers.

Keywords: AFB1; G2/M phase; Pathology Section; cell cycle arrest; jejunum; mechanism.

MeSH terms

  • Aflatoxin B1 / toxicity*
  • Animals
  • Ataxia Telangiectasia Mutated Proteins / metabolism*
  • Cell Division
  • Checkpoint Kinase 2 / metabolism
  • Chickens
  • Cyclin B1 / metabolism
  • Flow Cytometry
  • G2 Phase Cell Cycle Checkpoints / drug effects*
  • Immunohistochemistry
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / pathology
  • Intestinal Mucosa / physiopathology*
  • Jejunum / drug effects
  • Jejunum / metabolism
  • Jejunum / pathology
  • Jejunum / physiopathology*
  • Microvilli / drug effects
  • Poisons / toxicity*
  • Proliferating Cell Nuclear Antigen / metabolism
  • Signal Transduction / drug effects*
  • Tumor Suppressor Protein p53 / metabolism
  • cdc25 Phosphatases / metabolism

Substances

  • Cyclin B1
  • Poisons
  • Proliferating Cell Nuclear Antigen
  • Tumor Suppressor Protein p53
  • Aflatoxin B1
  • Checkpoint Kinase 2
  • Ataxia Telangiectasia Mutated Proteins
  • cdc25 Phosphatases