title: [Effects of chromosomal polyploidy on survival of colon cancer cells].
abstract: OBJECTIVE
  Tetraploid cells are frequently observed in the inflamed mucosal epithelial cells of the patients with Barrett's esophagus or chronic ulcerative colitis. Polyploidy often occurs during cell fusion, abortive cell cycle, and endoreplication. Most tetraploid cells are engaged to apoptotic pathway, but some remaining stable tetraploid cells consequently cause aneuploidization and chromosomal instability. We investigated whether tetraploid cells could acquire survival advantage and hold a dominant position for natural selection.
  
  
  METHODS
  We established tetraploid cell line (HCT116GH) from parental diploid colorectal cancer cell line (HCT116) via PEG-mediated cell fusion and compared its cell viability, cell cycle response and apoptotic fractions responded to H₂O₂) with diploid HCT116 and p53 suppressed HCT116/H6 cell lines.
  
  
  RESULTS
  Using MTT assay, plating efficiency and clonogenicity, we evaluated the survival of each cell line. Tetraploid cell line HCT116GH demonstrated an 83 fold greater resistance to 100 microM H₂O₂ than the parental diploid HCT116, and 6 fold greater than even the p53 negative diploid HCT116/E6. Cellular sensitivity, G2/M arrests, and apoptotic proportion were observed less in response to H₂O₂ in HCT116GH compared with HCT116 and HCT116/E6. HCT116GH expressed lower level of p53 and p21 than diploid HCT116.
  
  
  CONCLUSIONS
  Stable tetraploid cell lines showed enhanced viability in comparison to parental diploid cell lines. The enhanced viability observed in tetraploidization surpassed that from downregulation of p53. Frequent appearance of tetraploid cells in stressful condition can be caused by natural selection owing to their enhanced viability and may consequently contribute to cancer cell transformation.
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Sang Un
authors.initials: SU
authors.lastname: Park
authors.forename: Eun Sook
authors.initials: ES
authors.lastname: Choi
authors.forename: Yeon Sil
authors.initials: YS
authors.lastname: Jang
authors.forename: Seung-Hee
authors.initials: SH
authors.lastname: Hong
authors.forename: In-Hoo
authors.initials: IH
authors.lastname: Kim
authors.forename: Dong Kyung
authors.initials: DK
authors.lastname: Chang
mesh_terms: D017209:Apoptosis; D002455:Cell Division; D045744:Cell Line, Tumor; D002470:Cell Survival; D043171:Chromosomal Instability; D003110:Colonic Neoplasms / Q000235:genetics* / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D016195:G2 Phase; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D018384:Oxidative Stress; D011123:Polyploidy; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D016159:Tumor Suppressor Protein p53; D006861:Hydrogen Peroxide