title: Cellular effects of genotoxic stress and gene silencing of the checkpoint kinases in human oral cells.
abstract: BACKGROUND
  The human oral cells have different physiological properties and different origins in developmental stages. Mechanical, physiological, and chemical stress can cause damage and irritation during clinical treatment in various oral tissues.
  
  
  OBJECTIVE
  The effects of DNA damage response and gene silencing of checkpoint kinases (Chk1/2) is not unclear in oral primary and cancer cells.
  
  
  METHODS
  Treatment with doxorubicin involving DNA damage and gene silencing of Chk1/2 by shRNA constructs was performed in pulp, periodontal ligament, gingival tissues (HGF), and mouth epithelial carcinoma cells (KB).
  
  
  RESULTS
  The KB cells were more sensitive to genotoxic stress response than oral primary cells. Endogenous levels of Chk1/2 in KB cell were higher than in pulp cells. When doxorubicin was administered, Chk2 activation was induced in KB cell, but not in pulp cells. However, viability in KB cells did not decrease by the suppression of the checkpoint proteins, whereas primary cells were defective in gene silencing. When doxorubicin treatment and gene silencing were combined, both primary cells and KB cell were defective. Moreover, in case of KB cell, cell death was increased and activation of Chk2 was increased in doxorubicin dose-dependent.
  
  
  CONCLUSIONS
  These data indicate that not only stress response mechanism may be different in oral primary and cancer cells but also Chk1/2 proteins may have essential roles in oral primary cells. Based on these data, checkpoint proteins may be crucial drug targets for oral cancer therapy.
authors.affiliation: Laboratory of Cell Cycle and Signal Transduction, Department of NanoBioMedical Sciences, Dankook University, Chungnam, Korea.
authors.forename: Jae-Hoon
authors.initials: JH
authors.lastname: Ji
authors.forename: Young-Joo
authors.initials: YJ
authors.lastname: Jang
mesh_terms: D002277:Carcinoma / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D002470:Cell Survival; D000071877:Checkpoint Kinase 1; D064447:Checkpoint Kinase 2; D003603:Cytotoxins / Q000633:toxicity*; D004249:DNA Damage / Q000502:physiology; D003782:Dental Pulp / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000633:toxicity*; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology*; D020868:Gene Silencing; D018816:Genes, cdc / Q000187:drug effects / Q000502:physiology; D005881:Gingiva / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D009055:Mouth / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D009062:Mouth Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D010513:Periodontal Ligament / Q000187:drug effects / Q000201:enzymology; D011494:Protein Kinases / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D003603:Cytotoxins; D004317:Doxorubicin; D011494:Protein Kinases; D064447:Checkpoint Kinase 2; C000605867:CHEK1 protein, human; C578634:CHEK2 protein, human; D000071877:Checkpoint Kinase 1; D017346:Protein Serine-Threonine Kinases