K6/ODC transgenic mice as a sensitive model for carcinogen identification
Y Chen1, L C Megosh, S K Gilmour
1ODC Mouse Group Inc., Drexel Hill, PA 19026, USA. chen_odc@yahoo.com
Toxicology Letters
|July 25, 2000
Summary
A new K6/ODC transgenic mouse model shows high sensitivity for identifying genotoxic carcinogens. This model accurately predicts rodent bioassay results, aiding in chemical risk assessment and carcinogen identification.
Area of Science:
- Oncology
- Toxicology
- Genetics
Background:
- Ornithine decarboxylase (ODC) dysregulation is common in epithelial tumors.
- ODC overexpression is a sufficient condition for tumor promotion in murine skin.
Purpose of the Study:
- To develop and validate a sensitive K6/ODC transgenic mouse model for genotoxic carcinogen identification.
- To assess the model's concordance with established rodent bioassays.
Main Methods:
- Overexpression of ODC targeted to hair follicle keratinocytes in K6/ODC transgenic mice.
- Testing of ten known carcinogens and noncarcinogens.
- Dose-response studies with 7,12-dimethylbenz(a)anthracene (DMBA).
Main Results:
- The K6/ODC model demonstrated 100% concordance with 2-year rodent bioassays for ten tested chemicals.
- Two known human carcinogens were correctly identified as carcinogens in this model.
- Low-dose DMBA (2 nmol) induced tumors in 50% of mice within 8 weeks.
Conclusions:
- The K6/ODC transgenic mouse model is highly sensitive to topical genotoxic carcinogens.
- This model is a valuable tool for carcinogen identification and chemical risk assessment.
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