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KMID : 1204320090250040285
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Laboratory Animal Research
2009 Volume.25 No. 4 p.285 ~ p.293
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Guideline on the Alternative Methods for Carcinogenicity of Pharmaceuticals
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Kim Tae-Myoung
Kim Dae-Joong
Chai Hee-Youl
Ahn Byeong-Woo
Ryu Jae-Myun
Son Seung-Hwan
Shim Tae-Jin
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Abstract
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The correct prediction of human risk after exposure to chemical and physical compounds has long been a major challenge. For this, the lifetime bioassay using rats and mice is routinely used. However, over the years this assay has clearly come to reveal several drawbacks; for example, large numbers of animals are used, and the assays are slow, insensitive and expensive. Therefore, there is an urgent need for alternative, more valid, carcinogenicity assays. One specific approach in finding alternatives is the use of transgenic mice with modifications in genes associated with the development of cancer, thereby increasing their sensitivity to carcinogens. Generally, the transgenic mouse models could reliably predict the carcinogenic potential of compounds, and importantly, the number of false positives was reduced significantly. These marked advantages of transgenic mouse models have resulted in the FDA in the USA and the European CPMP now allowing the use of transgenic mice in regulatory testing of pharmaceutical compounds as an alternative for a second lifetime bioassay, when a two-year bioassay with rats was carried out. Nonetheless, a more extensive evaluation of transgenic mice using newly developed models and more compounds with different modes of action needs to be carried out in the future. These results of this comprehensive study suggest that some of these models might be useful in hazard identification if used in conjunction with information from other sources in a weight of evidence, integrated analysis approach to risk assessment.
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KEYWORD
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Alternative carcinogenicity test, carcinogenicity, transgenic mouse, medium-term bioassay
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