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CB6F1-rasH2 mouse: overview of available data
1Central Institute for Experimental Animals, Kawasaki, Japan. usui@ciea.or.jp
Toxicologic Pathology
|November 7, 2001
Summary
The rasH2 transgenic mouse model effectively identified genotoxic carcinogens and showed a low false-positive rate for non-genotoxic compounds in carcinogenicity testing. This model shows promise for alternative toxicity testing.
Area of Science:
- Toxicology
- Genetics
- Carcinogenesis
Background:
- The International Life Sciences Institute's (ILSI) Health and Environmental Sciences' (HESI) Alternative to Carcinogenicity Testing (ACT) project evaluated the CB6F1-rasH2 transgenic mouse.
- This study includes data from short-term carcinogenicity assessments using this model, alongside comparable external studies.
Purpose of the Study:
- To assess the utility of the rasH2 transgenic mouse model in carcinogenicity testing.
- To evaluate the model's performance in detecting genotoxic and non-genotoxic carcinogens.
Main Methods:
- Short-term carcinogenicity studies were conducted using the CB6F1-rasH2 transgenic mouse.
- Compounds tested included genotoxic carcinogens, non-genotoxic rodent carcinogens, human carcinogens, hormones, and non-carcinogens.
- Standardized and modified protocols were employed across participating laboratories.
Main Results:
- 3 of 4 genotoxic carcinogens tested were positive in the rasH2 mouse; one was equivocal.
- The positive control N-Methyl-N-nitrosurea (MNU) showed reproducible positive responses.
- Two peroxisome proliferators (clofibrate, DEHP) were positive among non-genotoxic rodent carcinogens; other non-genotoxic non-carcinogens were negative.
Conclusions:
- The rasH2 mouse model demonstrated efficacy in identifying genotoxic carcinogens.
- The model showed a low false-positive rate for non-genotoxic compounds, suggesting its reliability.
- These findings support the rasH2 mouse as a valuable tool for alternative carcinogenicity testing.