Please use this identifier to cite or link to this item:
Title: Use of a Multistrain Assay Could Improve the NTP Carcinogenesis Bioassay
Authors: Festing, Michael F. W.
First Published: Jan-1995
Publisher: National Institute of Environmental Health Sciences (NIEHS)
Citation: Environmental Health Perspectives 1995 Jan; 103(1): 44–52.
Abstract: There are often large strain differences in the response of laboratory animals to toxic chemicals and carcinogens, with some strains being totally resistant to dose levels that cause acute toxicity and/or cancer in other strains. The current National Toxicology Program carcinogenesis bioassay (NTP-CB) uses only a single isogenic strain of mice and rats and may therefore miss some carcinogens. New short-term tests to predict mutagenesis and possible carcinogenesis are validated using data from the NTP-CB. If the animal data are inaccurate, it may hinder this validation. The accuracy of the NTP-CB could be improved by using two or more strains of each species without increasing the total number of animals. It would be possible to continue to use sample sizes of 48-50 animals, but subdivide these into groups of 12 animals of 4 different strains (48 animals total) per dose/sex group, for example, instead of 48 identical animals. This would quadruple the number of genotypes without any substantial increase in cost. Such a multistrain "factorial" design would, on average, be statistically more powerful then the present design and should increase the chance of detecting carcinogens that currently may give equivocal results or go undetected because the test animal strains happen to be specifically resistant. When strains differ in response, studies of differences in metabolism, pharmacokinetics, DNA damage/repair, cellular responses, and in some cases identification of genetic loci governing sensitivity may provide biological information on toxic mechanisms that would help in assessing human risk and setting permissible exposure limits. The NTP may have made the world a safer place for F344 rats and B6C3F1 mice. The challenge now is to show that the results can be generalized to other genotypes and that the database can be used to validate short-term tests. A first step could be to explore the importance of strain differences in the carcinogenesis bioassay.
DOI Link: 10.2307/3432255
ISSN: 0091-6765
eISSN: 1552-9924
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Reproduced with permission from Environmental Health Perspectives.
Description: PMCID: PMC1519052
Appears in Collections:Published Articles, MRC Toxicology Unit

Files in This Item:
File Description SizeFormat 
envhper00350-0044.pdf2.87 MBAdobe PDFView/Open

Items in LRA are protected by copyright, with all rights reserved, unless otherwise indicated.