Radiation hormesis and dose response: Are our current concepts meaningful or useful?

Radiation hormesis is generally described in terms of a narrow dose range over which radiation appears to result in beneficial effects before becoming harmful as the dose increases. We suggest in this article that a different way of looking at the issue might be profitable. In particular, we suggest that low-dose mechanisms have been clearly shown to be different to high-dose mechanisms and to involve activation of communication and signaling pathways. These have very low induction thresholds and saturate at doses within the range of interest making the concept of ‘dose’ rather irrelevant. We propose that instead of framing models, mechanisms and indeed radiation protection within a dose framework, we need instead to consider a response framework. In experimental studies, low-dose response or ‘effect’ is actually what we measure, for example, mutation, proteomic changes, oxidative stress, mitochondrial changes, etc. but we describe them as ‘surrogates’ for dose despite being aware of wide individual variations. Perhaps we need to accept that different doses will provoke different responses that will be context dependent. ‘Dose’ and ‘dose rate’ becomes ‘response’ and ‘response rate’, and would be determined by the type of communication signalling that was activated. Such a response model would allow factors such as age, sex, nutrition, genetics, epigenetics, and biochemical/biophysical functionality to be considered as determinants of outcome in addition to the physical dose deposition. We suggest that a more useful holistic understanding of hormesis should result.