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ToxSci Advance Access originally published online on September 1, 2006
Toxicological Sciences 2006 94(2):368-378; doi:10.1093/toxsci/kfl098
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© The Author 2006. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Hormesis Outperforms Threshold Model in National Cancer Institute Antitumor Drug Screening Database

Edward J. Calabrese*,1, John W. Staudenmayer{dagger}, Edward J. Stanek, III{ddagger} and George R. Hoffmann§

* Department of Public Health, Environmental Health Sciences Program, Morrill I, N344, University of Massachusetts, Amherst, Massachusetts 01003 {dagger} Department of Mathematics and Statistics, Lederle Graduate Research Tower, University of Massachusetts, Amherst, Massachusetts 01003 {ddagger} Department of Public Health, Biostatistics and Epidemiology Program, School of Public Health and Health Sciences, Arnold House, University of Massachusetts, Amherst, Massachusetts 01003 § Department of Biology, College of the Holy Cross, O'Neil Hall, 107, Worcester, Massachusetts 01610-2395

Received March 31, 2006; accepted August 30, 2006

Which dose-response model best explains low-dose responses is a critical issue in toxicology, pharmacology, and risk assessment. The present paper utilized the U.S. National Cancer Institute yeast screening database that contains 56,914 dose-response studies representing the replicated effects of 2189 chemically diverse possible antitumor drugs on cell proliferation in 13 different yeast strains. Multiple evaluation methods indicated that the observed data are inconsistent with the threshold model while supporting the hormetic model. Hormetic response patterns were observed approximately four times more often than would be expected by chance alone. The data call for the rejection of the threshold model for low-dose prediction, and they support the hormetic model as the default model for scientific interpretation of low-dose toxicological responses.

Key Words: hormesis; threshold; dose-response; yeast; NCI; U-shaped; J-shaped; bell-shaped; risk assessment; carcinogens; chemotherapeutics; cell proliferation; Saccharomyces.


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