The relationship between the IC(50), toxic threshold, and the magnitude of stimulatory response in biphasic (hormetic) dose-responses.
Hormesis is a dose-response relationship characterized by a biphasic (U- or inverted U-shaped) response. We present the results of a study designed to assess the relationship between toxic potency (as measured by the IC(50)) and the magnitude of the hormesis stimulation. To facilitate this, we describe a new parameter (Delta(X)), which we define as the difference between the concentration (or dose) that inhibits 50% of the growth of the organism under study (IC(50)), and the concentration (or dose) of the respective toxicological threshold (either the benchmark dose (BMD) or zero equivalent point (ZEP)). Our analysis includes a subset of data from a previously published report describing a National Cancer Institute study that exposed yeast to putative anticancer agents in a high throughput assay. The toxic threshold used in this paper was the BMD(5). Thus, the Delta(X) in this paper is defined as: Delta(X)=IC(50)-BMD(5). We have found that the Delta(X) and the magnitude of stimulation above the control response are inversely related. These findings describe the first known relationship between toxic potency and the magnitude of hormetic response and warrant further inquiry.
Nascarella
Marc A
MA
Gradient Corporation, 20 University Road, Cambridge, MA 02138, USA. mnascarella@gradientcorp.com
Calabrese
Edward J
EJ
D000970:Antineoplastic Agents / Q000633:toxicity*; D003627:Data Interpretation, Statistical; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D020128:Inhibitory Concentration 50; D008954:Models, Biological; D012441:Saccharomyces cerevisiae / Q000187:drug effects
D000970:Antineoplastic Agents