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Related Experiment Videos

CB6F1-rasH2 mouse: overview of available data.

T Usui1, M Mutai, S Hisada

  • 1Central Institute for Experimental Animals, Kawasaki, Japan. usui@ciea.or.jp

Toxicologic Pathology
|November 7, 2001
PubMed
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.

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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.

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  • 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.