Integrating Adaptive Responses Into Hormesis: δ Plot Analysis of the Yonezawa Effect in the Micronucleus Test

Objectives Cells and organisms respond dynamically to environmental stimuli such as radiation and chemicals. Depending on the assay system, these responses have been described as hormesis, adaptive responses, J-shaped responses, and biphasic responses. In micronucleus assays using cultured cells, however, the intrinsically low baseline frequency of micronuclei makes it difficult to obtain a clear J-shaped dose–response curve characteristic of hormesis. To address this limitation, we conducted challenge and cross-challenge experiments. Methods In challenge tests, cells were first exposed to low priming doses and then to a high challenging dose. In cross-challenge tests, cells were pretreated with low doses of one chemical (e.g., mitomycin C) and subsequently exposed to a high dose of another (e.g., AF-2). Results In both approaches, pre-exposure suppressed micronucleus formation induced by the high dose. δ-Plot analysis was applied to quantify the Yonezawa effect, a well-established radiation-induced adaptive response. The data fit the δ-plot model well, indicating that the observed effects are consistent with hormesis as preconditioning. Conclusion Because “adaptive response” is overly broad and terms such as “J-shaped response” or “biphasic response” are overly narrow, we propose integrating these phenomena under the concept of hormesis, providing a unified framework for interpreting low-dose biological effects.