Hormesis redefined: Insights from application of δ plot quantification of the Yonezawa effect to dose responses in the micronucleus test

Cells and organisms respond dynamically to environmental factors like radiation and chemicals. These responses vary based on detection systems, leading to terms such as adaptive response, biphasic response, and hormesis. In micronucleus tests using cultured cells, obtaining a typical J-shaped dose-response curve, a hallmark of hormesis, was challenging due to low background micronucleus frequency. We conducted challenge and cross-challenge tests. In challenge tests, cells were pre-treated with low priming doses and then post-treated with a high challenging dose. In cross-challenge tests, cells were pre-treated with one chemical at low doses and then post-treated with a high dose of another chemical. Both tests showed clear suppression of micronucleus induction by high doses following pre-treatments. Our paper reporting hormesis in the micronucleus test was initially rejected, with reviewers claiming we detected an adaptive response rather than hormesis. Believing these concepts to be equivalent, we re-analyzed our data using the δ plot, which quantifies the Yonezawa effect, a type of radiation adaptive response. The analysis showed our results fit effectively with the δ plot. Since the Yonezawa effect aligns with the definition of hormesis, our findings could be termed as such. Other adaptive responses fitting the δ plot could also be considered hormesis.