Oral carcinogenesis is not achieved in different carcinogen-treated PAI-1 transgenic and wild-type mouse models

In Vivo. 2012 Nov-Dec;26(6):1001-5.

Abstract

Aim: 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.

Materials and 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.

Conclusion: Transgenic mice may respond differently when used in well-established carcinogen models and oral carcinogenesis is hard to achieve in these rodents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Nitroquinoline-1-oxide / toxicity
  • 9,10-Dimethyl-1,2-benzanthracene / toxicity
  • Animals
  • Carcinogens / toxicity
  • Cell Transformation, Neoplastic* / chemically induced
  • Cell Transformation, Neoplastic* / genetics
  • Cell Transformation, Neoplastic* / pathology
  • Enalapril / administration & dosage
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Mice
  • Mice, Transgenic
  • Mouth Neoplasms* / chemically induced
  • Mouth Neoplasms* / genetics
  • Mouth Neoplasms* / pathology
  • Neoplasms, Squamous Cell* / chemically induced
  • Neoplasms, Squamous Cell* / genetics
  • Neoplasms, Squamous Cell* / pathology
  • Pravastatin / administration & dosage
  • Serpin E2 / blood
  • Serpin E2 / genetics*

Substances

  • Carcinogens
  • Serpin E2
  • Serpine2 protein, mouse
  • 4-Nitroquinoline-1-oxide
  • 9,10-Dimethyl-1,2-benzanthracene
  • Enalapril
  • Pravastatin