Skip Navigation



ToxSci Advance Access published online on December 2, 2003
Toxicological Sciences, doi:10.1093/toxsci/kfh037
Toxicological Sciences © Society of Toxicology 2003; all rights reserved
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow All Versions of this Article:
77/2/188    most recent
kfh037v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by MacDonald, J.
Right arrow Articles by van der Laan, J. W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by MacDonald, J.
Right arrow Articles by van der Laan, J. W.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Received August 21, 2003; accepted November 3, 2003
© 2003 Society of Toxicology

Forum

The Utility of Genetically-Modified Mouse Assays for Identifying Human Carcinogens - A Basic Understanding and Path Forward

James MacDonald 1, John E. French 2, Ronald J. Gerson 3, Jay Goodman 4, Tohru Inoue 5, Abigail Jacobs 6, Peter Kasper 7, Douglas Keller 8, Amy Lavin 9*, Gerald Long 10, Bruce McCullough 11, Frank D. Sistare 6, Richard Storer 12, and Jan Willem van der Laan 13

1 Schering-Plough Research Institute, Kenilworth, NJ 07033
2 National Institute of Environmental Health Sciences, Research Triangle Park, NC, 27709
3 Endo Pharmaceuticals, Chadds Ford, PA, 19352
4 Michigan State University, East Lansing, MI 48824
5 National Institute of Health Sciences, Tokyo 158-8501, Japan
6 U.S. Food and Drug Administration, Center for Drug Evaluation and Research, Rockville, MD, 20857
7 Federal Institute for Drugs and Medical Devices (BfArM), D-53175 Berlin, Germany
8 Sanofi-Synthelabo Research, Malvern, PA, 19355
9 ILSI Health and Environmental Sciences Institute, Washington, DC 20005
10 Eli Lilly & Company, Greenfield, IN 46140
11 Aventis Pharmaceuticals, Inc. , Bridgewater, NJ, 08807
12 Merck Research Laboratories, West Point, PA, 19486
13 National Institute of Public Health and the Environment (RIVM), 3720 BA Bilthoven, The Netherlands

* To whom correspondence should be addressed. E-mail: alavin{at}ilsi.org.


  Abstract

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 .


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Toxicol SciHome page
A. Jacobs
Prediction of 2-Year Carcinogenicity Study Results for Pharmaceutical Products: How Are We Doing?
Toxicol. Sci., November 1, 2005; 88(1): 18 - 23.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
J. R. Bucher and C. Portier
Human Carcinogenic Risk Evaluation, Part V: The National Toxicology Program Vision for Assessing the Human Carcinogenic Hazard of Chemicals
Toxicol. Sci., December 1, 2004; 82(2): 363 - 366.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
A. Jacobs and D. Jacobson-Kram
Human Carcinogenic Risk Evaluation, Part III: Assessing Cancer Hazard and Risk in Human Drug Development
Toxicol. Sci., October 1, 2004; 81(2): 260 - 262.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol PatholHome page
J. T. Macgregor
Biomarkers of Cancer Risk and Therapeutic Benefit: New Technologies, New Opportunities, and Some Challenges
Toxicol Pathol, January 1, 2004; 32(1_suppl): 99 - 105.
[Abstract] [PDF]


Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.