title: Topical application of Aggregatibacter actinomycetemcomitans cytolethal distending toxin induces cell cycle arrest in the rat gingival epithelium in vivo.
abstract: BACKGROUND
  Aggregatibacter actinomycetemcomitans is one of the etiological pathogens implicated in the onset of periodontal disease. This pathogen produces cytolethal distending toxin (CDT) that acts as a genotoxin to induce cell cycle arrest and cellular distension in cultured cell lines. Therefore, CDT is a possible virulence factor; however, the in vivo activity of CDT on periodontal tissue has not been explored. Here, CDT was topically applied into the rat molar gingival sulcus; and the periodontal tissue was histologically and immunohistochemically examined.
  
  
  METHODS
  Recombinant purified A. actinomycetemcomitans CDT was applied to gingival sulcus of male Wistar rats and tissue samples were immunohistochemmically examined.
  
  
  RESULTS
  One day after application, infiltration of neutrophils and dilation of blood vessels in the gingival connective tissue were found. At day three, desquamation and detachment of cells in the junctional epithelium was observed. This abrasion of junctional epithelium was not observed in rats treated with mutated CDT, in which a His274Ala mutation is present in the CdtB subunit. This indicates the tissue abrasion may be caused by the genotoxicity of CdtB. Expression of the proliferating cell nuclear antigen (PCNA), a marker for proliferating cells, was significantly suppressed using CDT treatment in the junctional epithelium and gingival epithelium.
  
  
  CONCLUSIONS
  Using the rat model, these data suggest CDT intoxication induces cell cycle arrest and damage in periodontal epithelial cells in vivo.
authors.affiliation: Departments of Bacteriology, Hiroshima University Graduate School of Biomedical Sciences, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Ohara
authors.forename: M
authors.initials: M
authors.lastname: Miyauchi
authors.forename: K
authors.initials: K
authors.lastname: Tsuruda
authors.forename: T
authors.initials: T
authors.lastname: Takata
authors.forename: M
authors.initials: M
authors.lastname: Sugai
mesh_terms: D000287:Administration, Topical; D016976:Aggregatibacter actinomycetemcomitans / Q000378:metabolism*; D000818:Animals; D001427:Bacterial Toxins / Q000008:administration & dosage / Q000494:pharmacology*; D002196:Capillaries / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003238:Connective Tissue / Q000098:blood supply / Q000187:drug effects; D004846:Epithelial Attachment / Q000166:cytology / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects; D004926:Escherichia coli; D005881:Gingiva / Q000098:blood supply / Q000166:cytology / Q000187:drug effects*; D007150:Immunohistochemistry; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D023421:Models, Animal; D009153:Mutagens / Q000494:pharmacology; D020556:Neutrophil Infiltration / Q000187:drug effects; D018809:Proliferating Cell Nuclear Antigen / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014664:Vasodilation; D037521:Virulence Factors / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D001427:Bacterial Toxins; D008070:Lipopolysaccharides; D009153:Mutagens; D018809:Proliferating Cell Nuclear Antigen; D037521:Virulence Factors; C067044:cytolethal distending toxin