Hormesis outperforms threshold model in National Cancer Institute antitumor drug screening database.
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.
Calabrese
Edward J
EJ
Department of Public Health, Environmental Health Sciences Program, Morrill I, N344, University of Massachusetts, Amherst, Massachusetts 01003, USA. edwardc@schoolph.umass.edu
Staudenmayer
John W
JW
Stanek
Edward J
EJ
Hoffmann
George R
GR
D000818:Animals; D000970:Antineoplastic Agents / Q000145:classification / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D008954:Models, Biological; D009316:National Institutes of Health (U.S.); D018570:Risk Assessment; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics; D014481:United States
D000970:Antineoplastic Agents