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CB6F1-rasH2 Mouse: Overview of Available Data
Toshimi Usui
Central Institute for Experimental Animals, Kawasaki, 216-0001, Japan, usui{at}ciea.or.jp
Mamoru Mutai
Mitsubishi-Tokyo Pharmaceuticals, Inc., Yokohama, 227-0033, Japan
Shigeru Hisada
Teikoku Hormone Mfg. Co. Ltd., Kawasaki, 213-8522, Japan
Masaya Takoaka
Sankyo Co. Ltd., Shizuoka, 437-0065, Japan
Keith A. Soper
Merck & Co., Inc., West Point, Pennsylvania 19486, USA
Bruce Mccullough
Aventis Pharmaceuticals, Bridgewater, New Jersey, 08807-0800, USA
Carl Alden
Millenium Pharmaceuticals, Boston, MA, USA
This article presents data from short-term carcinogenicity studies of compounds tested in the CB6F1-rasH2 transgenic mouse as part of the International Life Sciences Institutes' (ILSI) Health and Environmental Sciences' (HESI) Alternative to Carcinogenicity Testing (ACT) project. Additionally, data from other studies that were not conducted as part of the ILSI program, but used comparable or slightly modifi ed protocols, are included here. A signifi cant number (3 of 4) of the genotoxic carcinogens tested were positive in the rasH2 mouse; the other compound was equivocally positive. The positive control, N-Methyl-N-nitrosurea (MNU), gave reproducible responses across all participating laboratories with tumors noted at multiple sites in the animal. The immunosuppressive human carcinogen, Cyclosporin A, was equivocal. Two hormones that are human tumorigens, Diethylstilbestrol and 17β-Estradiol, gave positive and negative results, respectively. Of the twelve additional compounds tested that are classifi ed as non-genotoxic rodent carcinogens and putative human non-carcinogens, only the two peroxisome proliferators (clofi brate and diethylhexylphthalate(DEHP)) produced a positive response (liver effects). The three non-genotoxic non-carcinogens that were tested also gave negative responses in the rasH2 model. This result provides confi dence that the model is likely to have a low false-positive rate.
Key Words: cHa ras proto-oncogene • transgenic mouse • bioassay • short-term • 26-Weeks • alternatives • carcinogenicity testing.
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Toxicologic Pathology, Vol. 29, No. 1 suppl,
90-108 (2001)
DOI: 10.1080/019262301753178500
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