Hormetic mechanisms.

This article provides the first extensive documentation of mechanisms of hormetic dose/concentration responses. The mechanisms selected were principally those mediated via receptor and/or cell signaling pathways. Mechanisms are reported for greater than 100 agents affecting nearly 400 dose/concentration responses from a wide range of chemical classes, affecting a broad range of cell types and endpoints. Regardless of the model (i.e. in vitro or in vivo), inducing agent, endpoint, or receptor/cell signaling pathway mediated mechanism, the quantitative features of the hormetic dose/concentration responses are similar, suggesting that the magnitude of the response is a measure of biological plasticity, within a broad range of biological contexts. These findings represent an important advance in the understanding of the hormetic dose/concentration response, its generalizability and potential biomedical applications, including drug discovery/efficacy assessment and the risk assessment process.