title: Oral carcinogenesis is not achieved in different carcinogen-treated PAI-1 transgenic and wild-type mouse models.
abstract: OBJECTIVE
  In an effort to assess the role of plasminogen activator inhibitor-1 (PAI-1) in oral squamous cancer development and progression, two different carcinogen treatment protocols were conducted.
  
  
  METHODS
  Protocol I included mice from a PAI-1 transgenic (Tg) breed (n=56) and their wild-type (WT) counterparts (n=56), divided into one control group and two main experimental groups, treated with 7,12-dimethylbenz[a]anthracene (DMBA) for 8 and 16 weeks, respectively. Protocol II included the same number and types of animals and groups, which were similarly treated with 4-Nitroquinoline 1-oxide (4-NQO) in drinking water. Two drugs that affect plasma PAI-1 levels, enalapril and pravastatin, were administered to certain subgroups of animals in both protocols.
  
  
  RESULTS
  None of the animals developed macroscopically-visible oral cancer lesions. Eleven animals under Protocol I and 52 animals under Protocol II died. Skin lesions were noted only in DMBA-treated animals (n=9). Almost all animals administered with 4-NQO developed alopecia and lost weight, while two of them developed stomach tumours, and one female mouse developed a large ovarian cyst.
  
  
  CONCLUSIONS
  Transgenic mice may respond differently when used in well-established carcinogen models and oral carcinogenesis is hard to achieve in these rodents.
authors.affiliation: Department of Oral and Maxillofacial Surgery, University of Athens Medical School, Attikon Hospital, Athens, Greece.
authors.forename: Dimitris
authors.initials: D
authors.lastname: Avgoustidis
authors.forename: Themistoklis
authors.initials: T
authors.lastname: Nisyrios
authors.forename: Emeka
authors.initials: E
authors.lastname: Nkenke
authors.forename: Roger
authors.initials: R
authors.lastname: Lijnen
authors.forename: Vassilis
authors.initials: V
authors.lastname: Ragos
authors.forename: Despina
authors.initials: D
authors.lastname: Perrea
authors.forename: Ismini
authors.initials: I
authors.lastname: Donta
authors.forename: Apostolia
authors.initials: A
authors.lastname: Vaena
authors.forename: Christos
authors.initials: C
authors.lastname: Yapijakis
authors.forename: Eleftherios
authors.initials: E
authors.lastname: Vairaktaris
mesh_terms: D015112:4-Nitroquinoline-1-oxide / Q000633:toxicity; D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D000818:Animals; D002273:Carcinogens / Q000633:toxicity; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced / Q000235:genetics / Q000473:pathology; D004656:Enalapril / Q000008:administration & dosage; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009062:Mouth Neoplasms / Q000139:chemically induced / Q000235:genetics / Q000473:pathology; D018307:Neoplasms, Squamous Cell / Q000139:chemically induced / Q000235:genetics / Q000473:pathology; D017035:Pravastatin / Q000008:administration & dosage; D058258:Serpin E2 / Q000097:blood / Q000235:genetics*
chemical_list: D002273:Carcinogens; D058258:Serpin E2; C511869:Serpine2 protein, mouse; D015112:4-Nitroquinoline-1-oxide; D015127:9,10-Dimethyl-1,2-benzanthracene; D004656:Enalapril; D017035:Pravastatin