Mouse skin models for carcinogenic hazard identification: Utilities and challenges

Dave Lynch, Jessica Svoboda, Sumanth Putta, Hans E J Hofland, Wendy H. Chern, Laura A. Hansen

Research output: Contribution to journalReview article

18 Scopus citations

Abstract

This report addresses 1) the predictability of mouse skin models for carcinogenic hazard identification, 2) the association between early changes in the skin and later tumorigenic responses, and 3) the relative sensitivity of three mouse models of skin tumorigenesis; i.e. the genetically-initiated Tg.AC and RasH2 lines and the SENCAR mouse model. All three mouse models responded similarly, with mild inflammation and epidermal hyperplasia, to several weeks of treatment with a topical agent. Based on our previous research experience, we hypothesized that inflammation, irritation, proliferation, and/or hyperplasia in the skin would precede and predict the appearance of tumors in these sensitive mouse skin models. Consistent with our hypothesis, the test agent caused a low but significant tumorigenic response in Tg.AC mice. We propose that inflammation, irritation, and hyperplasia are sensitive predictors of a later tumorigenic response in Tg.AC mice. Further studies are needed, however, to better determine the relative sensitivity of these 3 models to a wider variety of agents.

Original languageEnglish
Pages (from-to)853-864
Number of pages12
JournalToxicologic Pathology
Volume35
Issue number7
DOIs
Publication statusPublished - Dec 2007

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All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Toxicology
  • Health, Toxicology and Mutagenesis

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