Hormesis Predicts Low-Dose Responses Better Than Threshold Models

Abstract

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.