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KMID : 1204320070230030239
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Laboratory Animal Research
2007 Volume.23 No. 3 p.239 ~ p.243
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Two Step Carcinogen Screening Model Using Neonatal FVB/NJ Mouse
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Won Young-Suk
Choi Yang-Kyu
Park Hyun-Ji
Nam Ki-Hoan
Kim Hyoung-Chin
Kwon Hyo-Jung
Jeong Eui-Suk
Koo Bon-Chul
Moon Oc-Sung
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Abstract
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A long-term carcinogenicity study is required to assess the safety of new drug candidates. This classical toxicological method has been using rats and mice as animal systems. The International Conference on Harmonization (ICH) of technical requirements of pharmaceuticals for human use have recommended one long-term rodent carcinogenicity test using rat and one other supplementary mouse study such as an initiation-promotion model, a transgenic model or a neonatal model. This study was carried out to develop an initiation-promotion liver carcinogenicity model using a mouse. Twelve-day old FVB/NJ mice were intraperitoneally injected with diethyl nitrosamine (DEN) as an initiator and orally administered with 2-acetlyaminofluorene (2-AAF) as a promoter. And o-galactosamine (DGA) was injected as a stimulator for tumorigenic progress. Basophilic foci in the liver were observed 16 weeks after initiation. The incidence of hepatocellular adenoma was increased in animals 2-AAF-treated at 20 and 26 weeks after initiation. The tumor incidence in 2-AAF-treated animals were significantly higher than with the untreatment and initiator treatment control groups. Hepatocellular carcinoma (HCC) was found in some cases. These results suggest that two-step neonatal FVB/NJ mouse model could be useful for carcinogenic assay of new drug candidates.
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KEYWORD
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FVB/NJ, carcinogenesis, hepatocellular adenoma, 2-acetlyaminofluorene(2-AAF)
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