Low dose radiation mechanisms: The certainty of uncertainty

Mothersill, Carmel; Seymour, Colin

doi:10.1016/j.mrgentox.2022.503451

Cited by 12 publications

(21 citation statements)

References 62 publications

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“…They conclude by concurring with the position on bystander phenomena stated in the UNSCEARWhite Paper (2012) that there is little of the coherence required of robust data among bystander studies that can be used confidently for risk assessment. We would argue, as did Mothersill and Seymour (2022b), that uncertainty of low-dose outcomes is a fact of life and indicates that factors other than radiation influence outcomes such as carcinogenesis. Rather than trying to determine whether bystander effects are relevant to cancer risk assessment, a better question would be "Which of the many competing risk and benefit factors actually wins and why?…”

Section: Introductionmentioning

confidence: 87%

“…several recent reviews have highlighted the difference in mechanisms underlying low-dose radiation effects when compared with high dose mechanisms (Khan and Wang 2022; Mothersill and Seymour 2022a and b; Narasimhamurthy et al 2022). Low dose is defined here using the ICRP Publication 103 recommendations (2007) as <100 mGy dose or < 6 mGy h −1 dose rate.…”

Section: Introductionmentioning

confidence: 99%

“…Crucial to the acceptance of the “separate mechanisms” argument was the discovery and mechanistic characterization of non-targeted effects (NTE). These are seen in cells, tissues, and organisms that were never exposed to radiation and thus never actually received an energy deposition from ionizing radiation in a target (for recent reviews and keystone papers see Mothersill and Seymour 1997, 1998, 2022b, 2022a; Azzam et al 2001; Maguire et al 2005; Murphy et al 2005; Shao et al 2006; Lyng et al 2006b; Chen et al 2008; Nugent et al 2010; Mothersill et al 2010, 2012, 2022c; Le et al 2017, 2018b; Gonon et al 2022; Jokar et al 2022; Smolarz et al 2022; Verma and Tiku 2022; Buonanno et al 2023; Tang et al 2023). The recent UNSCEAR report (Annex C 2021) discusses the biological mechanisms and processes with could impact inference of cancer risk.…”

Section: Introductionmentioning

confidence: 99%

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Factors Influencing Effects of Low-dose Radiation Exposure

Mothersill,

Seymour,

Cocchetto

et al. 2024

Health Physics

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It is now well accepted that the mechanisms induced by low-dose exposures to ionizing radiation (LDR) are different from those occurring after high-dose exposures. However, the downstream effects of these mechanisms are unclear as are the quantitative relationships between exposure, effect, harm, and risk. In this paper, we will discuss the mechanisms known to be important with an overall emphasis on how so-called “non-targeted effects” (NTE) communicate and coordinate responses to LDR. Targeted deposition of ionizing radiation energy in cells causing DNA damage is still regarded as the dominant trigger leading to all downstream events whether targeted or non-targeted. We regard this as an over-simplification dating back to formal target theory. It ignores that last 100 y of biological research into stress responses and signaling mechanisms in organisms exposed to toxic substances, including ionizing radiation. We will provide evidence for situations where energy deposition in cellular targets alone cannot be plausible as a mechanism for LDR effects. An example is where the energy deposition takes place in an organism not receiving the radiation dose. We will also discuss how effects after LDR depend more on dose rate and radiation quality rather than actual dose, which appears rather irrelevant. Finally, we will use recent evidence from studies of cataract and melanoma induction to suggest that after LDR, post-translational effects, such as protein misfolding or defects in energy metabolism or mitochondrial function, may dominate the etiology and progression of the disease. A focus on such novel pathways may open the way to successful prophylaxis and development of new biomarkers for better risk assessment after low dose exposures.

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Section: Introductionmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Factors Influencing Effects of Low-dose Radiation Exposure

Mothersill,

Seymour,

Cocchetto

et al. 2024

Health Physics

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“…A greater understanding of the steps involved in the signaling process might make outcomes more predictable. The issue of uncertainty is discussed in Mothersill and Seymour 2022 [ 20 ]. These ideas are fiercely unpopular among those who wish to promote a threshold model of radiation protection because any possibility that radiation might cause any adverse low dose effects, means that a precautionary approach is likely to be retained when setting dose limits [ 21 , 22 , 23 , 24 ].…”

Section: Introduction To Low Dose and Non-targeted Radiobiologymentioning

confidence: 99%

“…Our laboratory first became interested in the possibility of acoustic signalling as a form of ionising radiation-induced bystander communication when studying the mechanism of fish to fish bystander signalling. A test involving putting irradiated fish in a small aquarium inside a larger aquarium containing non-irradiated fish demonstrated that the signal could pass through glass (discussed in [ 20 ]). This provided the first evidence that a water-bourn chemical did not mediate the transmission of the signal in these experiments.…”

Section: Introduction To Low Dose and Non-targeted Radiobiologymentioning

confidence: 99%

Low Dose and Non-Targeted Radiation Effects in Environmental Protection and Medicine—A New Model Focusing on Electromagnetic Signaling

Mothersill

Cocchetto

Seymour

2022

IJMS

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The role of signalling in initiating and perpetuating effects triggered by deposition of ionising radiation energy in parts of a system is very clear. Less clear are the very early steps involved in converting energy to chemical and biological effects in non-targeted parts of the system. The paper aims to present a new model, which could aid our understanding of the role of low dose effects in determining ultimate disease outcomes. We propose a key role for electromagnetic signals resulting from physico-chemical processes such as excitation decay, and acoustic waves. These lead to the initiation of damage response pathways such as elevation of reactive oxygen species and membrane associated changes in key ion channels. Critically, these signalling pathways allow coordination of responses across system levels. For example, depending on how these perturbations are transduced, adverse or beneficial outcomes may predominate. We suggest that by appreciating the importance of signalling and communication between multiple levels of organisation, a unified theory could emerge. This would allow the development of models incorporating time, space and system level to position data in appropriate areas of a multidimensional domain. We propose the use of the term “infosome” to capture the nature of radiation-induced communication systems which include physical as well as chemical signals. We have named our model “the variable response model” or “VRM” which allows for multiple outcomes following exposure to low doses or to signals from low dose irradiated cells, tissues or organisms. We suggest that the use of both dose and infosome in radiation protection might open up new conceptual avenues that could allow intrinsic uncertainty to be embraced within a holistic protection framework.

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