The utility of genetically modified mouse assays for identifying human carcinogens: a basic understanding and path forward. The Alternatives to Carcinogenicity Testing Committee ILSI HESI.
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.
MacDonald
James
J
Schering-Plough Research Institute, Kenilworth, New Jersey 07033, USA.
French
John E
JE
Gerson
Ronald J
RJ
Goodman
Jay
J
Inoue
Tohru
T
Jacobs
Abigail
A
Kasper
Peter
P
Keller
Douglas
D
Lavin
Amy
A
Long
Gerald
G
McCullough
Bruce
B
Sistare
Frank D
FD
Storer
Richard
R
van der Laan
Jan Willem
JW
D000818:Animals; D030801:Animals, Genetically Modified; D015197:Carcinogenicity Tests / Q000379:methods* / Q000592:standards; D002273:Carcinogens / Q000633:toxicity; D016158:Genes, p53; D011905:Genes, ras; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D023421:Models, Animal; D018570:Risk Assessment
D002273:Carcinogens