ToxSci Advance Access originally published online on December 2, 2003
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Toxicological Sciences 77, 188-194 (2004)
Copyright © 2004 by the Society of Toxicology
FORUM |
The Utility of Genetically Modified Mouse Assays for Identifying Human Carcinogens: A Basic Understanding and Path Forward
* Schering-Plough Research Institute, Kenilworth, New Jersey 07033;
National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709;
Endo Pharmaceuticals, Chadds Ford, Pennsylvania 19352;
Michigan State University, East Lansing, Michigan 48824;
¶ National Institute of Health Sciences, Tokyo 158-8501, Japan;
|| U.S. Food and Drug Administration, Center for Drug Evaluation and Research, Rockville, Maryland 20857;
||| Federal Institute for Drugs and Medical Devices (BfArM), D-53175 Berlin, Germany;
|||| Sanofi-Synthelabo Research, Malvern, Pennsylvania 19355;
# ILSI Health and Environmental Sciences Institute, Washington, DC 20005;
** Eli Lilly & Company, Greenfield, Indiana 46140;
Aventis Pharmaceuticals, Inc., Bridgewater, New Jersey 08807;
Merck Research Laboratories, West Point, Pennsylvania, 19486; and
National Institute of Public Health and the Environment (RIVM), 3720 BA Bilthoven, The Netherlands
The Alternatives to Carcinogenicity Testing Committee of the International Life Sciences Institute (ILSI) Health and Environmental Sciences Institute (HESI) conducted a large-scale, multinational collaborative research program to evaluate several genetically modified mouse assays for assessing the human carcinogenic potential of compounds. The data from this testing program have made an important contribution to the general understanding of how these models can be best applied in hazard identification; however, questions still exist regarding methodology and data interpretation. To address these issues, ILSI HESI hosted a February 2003 workshop on the Utility of Transgenic Assays for Risk Assessment. The purpose of this workshop was to reach an understanding of how data from genetically modified mouse models are viewed by different regulatory bodies in the pharmaceutical sector and, based on this understanding, to identify areas in which more experimental work may be needed to increase the utility of data derived from these assays. In the course of discussions, various data gaps related to model selection and protocol issues were identified. Based on the outcome of the workshop, various studies are proposed to provide data to improve the utility of currently available assays for cancer hazard identification and risk assessment purposes.
Key Words: carcinogenicity; p53+/-; knockout mouse; regulatory perspective; risk assessment; Tg.rasH2 transgenic mouse; genetically modified mice.
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