Hormesis: A generalizable and unifying hypothesis

The present article represents a comprehensive effort to assess the hypothe sis that hormesis is a highly generalizable biological phenomenon independe nt of environmental stressor, biological endpoint, and experimental model s ystem. The evaluative methodology and complementary approaches employed to assess this question are (1) evolutionary biology-based theoretical paradig m; (2) evaluation of > 20,000 toxicology articles using a priori entry and evaluative criteria; (3) evaluation of 17 large-scale studies each providin g data on numerous agents tested in the same experimental model by the same research team; (4) the assimilation of experimental pharmacological data o n 24 receptor systems in which biphasic dose responses have been establishe d reproducibly along with hormetic mechanism elucidation; and (5) assessmen t of the original hormesis database with 1600 dose-response relationships d emonstrating evidence consistent with the hormesis hypothesis. The compleme ntary approaches for assessing hormesis provided strong support for its cre dibility as a central biological theory based on its high frequency of occu rrence and quantitative features of expression within microbe, plant, and i nvertebrate and vertebrate animal systems. The findings suggest that hormet ic effects represent evolutionary-based adaptive responses to environmental ly induced disruptions in homeostasis. Such adaptive responses, which are i ncorporated into organismal integrative physiological systems and now clari fied at the mechanistic level for more than two dozen receptor systems, pro vide a cogent basis for the application of hormetic mechanisms in the eluci dation of fundamental evolutionary-based biological processes and in the de velopment of novel clinical modalities.