title: Effects of 4-nonylphenol on proliferation of AGS gastric cells.
abstract: OBJECTIVE
  Nonylphenol (NP) is present ubiquitously in both aquatic and terrestrial environments. This compound is considered an important endocrine disruptor and its toxic/oestrogenic activity has been investigated in a number of in vitro and in vivo studies. Human exposure to NP may occur by cutaneous absorption, ingestion of contaminated food or water and inhalation. Moreover, while the cytotoxic effects of NP are known and studied, its effects on cell death and related mechanisms are not known. Our group decided to investigate NP effects on a gastric epithelial cell line (AGS), in particular NP effects on AGS cell cycle and apoptosis.
  
  
  METHODS
  Cell cycle was analysed by flow cytometry, p21 and p27 induction, and apoptosis was analysed by flow cytometry and annexin-V assays, Fas, Fas-L, caspase 8 and caspase 3 activation.
  
  
  RESULTS
  We have demonstrated that NP affected cell cycle and apoptosis in a time- and dose-dependent manner, reaching the most notable effect at concentration of 10(-7)m, for 48 h. Flow cytometry revealed that treatment with 10(-7) m NP led to accumulation of cells at G(2) /M transition and increased percentage population of apoptotic cells. Results have shown that NP at concentration 10(-7) m induced marked increase in Fas and Fas-L expression. Moreover, 10(7) m NP induced activation of caspases 8 and 3, but not activation of caspase 9.
  
  
  CONCLUSIONS
  The results reported suggest that gastric cells can be useful as screening population for appropriate study of developmental toxicity.
authors.affiliation: Department of Medicine and Public Health, Section of Human Anatomy, Second University of Naples, Naples, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Manente
authors.forename: A
authors.initials: A
authors.lastname: Sellitti
authors.forename: A
authors.initials: A
authors.lastname: Lucariello
authors.forename: V
authors.initials: V
authors.lastname: Laforgia
authors.forename: M
authors.initials: M
authors.lastname: De Falco
authors.forename: A
authors.initials: A
authors.lastname: De Luca
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D052244:Endocrine Disruptors / Q000633:toxicity*; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D053222:Fas Ligand Protein / Q000378:metabolism; D005506:Food Contamination; D005753:Gastric Mucosa / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D010636:Phenols / Q000633:toxicity*; D016160:Retinoblastoma Protein / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism
chemical_list: D052244:Endocrine Disruptors; C491901:FAS protein, human; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D010636:Phenols; D016160:Retinoblastoma Protein; D019014:fas Receptor; C505407:CASP3 protein, human; D053148:Caspase 3; C041594:4-nonylphenol