1. Mouse skin models for carcinogenic hazard identification: utilities and challenges
- Author
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Dave Lynch, Laura A. Hansen, Hans E. J. Hofland, Chern Wendy Huang, Jessica Svoboda, and Sumanth K. Putta
- Subjects
Skin Neoplasms ,040301 veterinary sciences ,Inflammation ,Mice, Transgenic ,Toxicology ,medicine.disease_cause ,030226 pharmacology & pharmacy ,Pathology and Forensic Medicine ,0403 veterinary science ,03 medical and health sciences ,Mice ,0302 clinical medicine ,medicine ,Biomarkers, Tumor ,Animals ,Molecular Biology ,Carcinogen ,integumentary system ,business.industry ,Keratin-6 ,04 agricultural and veterinary sciences ,Cell Biology ,Hyperplasia ,medicine.disease ,Test agent ,SENCAR Mouse ,Immunology ,Mouse skin ,Models, Animal ,Carcinogens ,medicine.symptom ,Irritation ,Carcinogenesis ,business - 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.
- Published
- 2007