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Hormesis Predicts Low-Dose Responses Better Than Threshold Models

Department of Public Health, Environmental Health Sciences Division, University of Massachusetts, Amherst, Massachusetts, USA

Edward J. Stanek, III

Department of Public Health, Biostatistics and Epidemiology Division, University of Massachusetts, Amherst, Massachusetts, USA

Marc A. Nascarella

Department of Public Health, Environmental Health Sciences Division, University of Massachusetts, Amherst, Massachusetts, USA

George R. Hoffmann

Department of Biology, College of the Holy Cross, Worcester, Massachusetts, USA

Correspondence: Address correspondence to Edward J. Calabrese, Department of Public Health, Environmental Health Sciences, Morrill I, N344, University of Massachusetts, Amherst, MA 01003, USA. E-mail:edwardc{at}schoolph.umass.edu

This study evaluated characteristics of the concentration-response relationships of chemicals from the U.S. National Cancer Institute (NCI) Yeast Anticancer Drug Screen database with respect to the threshold and the hormetic dose-response models. The database reported concentration-response studies of 2189 chemicals from a broad range of chemical classes. The biological end point was growth in 13 strains of yeast (Saccharomyces cerevisiae), most of which contain genetic alterations affecting DNA repair or cell cycle control. The analysis was limited to studies that satisfied a priori entry criteria for evaluation, including having two or more concentrations in the nontoxic zone (below a Benchmark Dose). The mean growth response compared to untreated controls of these doses was significantly greater than 100% in all 13 yeast strains, ranging from ~105% to ~111%. Under a threshold model, one would expect values more closely approximating 100%. Moreover, the distribution of responses below the BMD₅ for chemicals was shifted upwardly from the expectations of a threshold model for all strains. These results indicate that for the chemicals and yeast strains studied, the responses are more consistent with a hormetic model than a threshold model, and they strengthen previous results presented by Calabrese et al. (2006, Toxicol. Sci. 94:368–378). Taken together, the analyses provide strong evidence for hormesis, a phenomenon with a broad range of biomedical and toxicological implications.

Key Words: Antitumor • Biphasic • Hormesis • Low Dose • Threshold • Yeast

International Journal of Toxicology, Vol. 27, No. 5, 369-378 (2008)
DOI: 10.1080/10915810802503735


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