Dose effect relationship and estimation of the carcinogenic effects of low doses of ionising radiation: the Joint Report of the Academie des Sciences (Paris) and of the Academie Nationale de Medecine

This paper reviews physical, experimental and epidemiological evidence for and against radiation hormesis and discusses implications with regards to radiation protection. The scientific community is still divided on the premise of radiation hormesis, with new literature published on a regular basis. The International Commission on Radiological Protection (ICRP) recommends the use of the Linear No Threshold (LNT) model, for planning radiation protection. This model states that the probability of induced cancer and hereditary effects increases with dose in a linear fashion. As a consequence, all radiation exposures must be justified and have a sufficient protection standard in place so that exposures are kept below certain dose limitations. The LNT model has sufficient evidence at high doses but has been extrapolated in a linear fashion to low dose regions with much less scientific evidence. Much experimentation has suggested discrepancies of this extrapolation at low doses. The hypothesis of radiation hormesis suggests low dose radiation is beneficial to the irradiated cell and organism. There is definite standing ground for the hormesis hypothesis both evolutionarily and biophysically, but experimental evidence is yet to change official policies on this matter. Application of the LNT model has important radiation protection and general human health ramifications, and thus it is important that the matter be resolved.

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“…38,40,48 ). They often give practical views on the matter and are sometimes accompanied by recommended radiation protection standards 11 .…”

Section: Rejection Of Radiation Hormesismentioning

confidence: 99%

A brief review of radiation hormesis

Jolly

Meyer

2009

Australas. Phys. Eng. Sci. Med.

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“…Initiation, thought to be due to oncogenic mutations from mis-repaired double DNA breaks, is widely believed to be the critical event for radiation carcinogenesis (16), however host systemic and stromal responses can also contribute to radiation’s carcinogenic potential (17–20). To test whether host biology contribute to radiation carcinogenesis, we established a radiation chimera model that separates radiation effects on the host from those on the target epithelium (21).…”

Section: Introductionmentioning

confidence: 99%

Murine Microenvironment Metaprofiles Associate with Human Cancer Etiology and Intrinsic Subtypes

Nguyen

Fredlund

Zhao

et al. 2013

Clinical Cancer Research

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Purpose Ionizing radiation is a well established carcinogen in rodent models and a risk factor associated with human cancer. We developed a mouse model that captures radiation effects on host biology by transplanting unirradiated Trp53 null mammary tissue to sham or irradiated hosts. Gene expression profiles of tumors that arose in irradiated mice are distinct from those that arose in naïve hosts. We asked whether expression metaprofiles could discern radiation-preceded human cancer or be informative in sporadic breast cancers. Experimental Design Affymetrix microarray gene expression data from 56 Trp53 null mammary tumors were used to define gene profiles and a centroid that discriminate tumors arising in irradiated hosts. These were applied to publicly available human cancer data sets. Results Host irradiation induces a metaprofile consisting of gene modules representing stem cells, cell motility, macrophages and autophagy. Human orthologs of the host irradiation metaprofile discriminated between radiation-preceded and sporadic human thyroid cancers. An irradiated host centroid was strongly associated with estrogen receptor negative breast cancer. When applied to sporadic human breast cancers, the irradiated host metaprofile strongly associated with basal-like and claudin-low breast cancer intrinsic subtypes. Comparing host irradiation in the context of TGFβ levels showed that inflammation was robustly associated with claudin-low tumors. Conclusions Detection of radiation-preceded human cancer by the irradiated host metaprofile raises possibilities of assessing human cancer etiology. Moreover, the association of the irradiated host metaprofiles with estrogen receptor negative status and claudin-low subtype suggests that host processes similar to those induced by radiation underlie sporadic cancers.

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“…This may be an oversimplification, however, if an exaggeration of perceived risks hinders the development or use of valuable diagnostic or therapeutic procedures, as has been suggested in the Joint Report of the French Academies in its argument against linear nonthreshold extrapolation for ionizing radiation. 32 The hormesis model ( Figure 1C), unlike the linear and threshold models, offers the possibility of two objectives -avoidance of harm associated with the toxic zone and reaping the benefit of the hormetic zone. If the hormesis concept were to be used as a basis for policy in a way that attempted to derive benefit from the hormetic zone, it would necessitate a corresponding shift in the ethical principle behind public policy.…”

Section: Challenges For Risk Assessmentmentioning

confidence: 99%

The hormesis concept and risk assessment: are there unique ethical and policy considerations?

Stempsey

2008

Hum Exp Toxicol

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The hormesis concept holds that low doses of toxic substances and radiation elicit modest biological responses opposite to those caused by higher doses of the same agents. This concept stands in contrast to the prevailing views that a threshold model predicts most responses to toxicants at low doses and that linear extrapolation best predicts mutagenic and carcinogenic responses. Beyond the scientific considerations, there has been concern that inclusion of the hormesis model in risk assessment would raise complex ethical questions, pose serious challenges for policy makers, and threaten public safety. This article briefly reviews the growing evidence for hormesis and offers a perspective on the related ethical and societal issues. Complexities stem from the nature of biphasic curves, in which biological responses fall both above and below background levels. The monotonic responses of the threshold and linear models lend themselves to a single policy objective – avoiding harm associated with exposures. The biphasic responses of the hormesis model, however, suggest the possibility of accruing benefit as well as avoiding harm. The prospect of applying the hormesis model to public health policy is impeded by insufficient ability to identify the hormetic and toxic zones with precision. Moreover, heterogeneity among individuals in susceptibility to toxicants suggests that benefit and risk may be distributed unequally in the population. The potential shift in policy objectives associated with hormesis is considered relative to the difficulty of balancing the ethical principles of nonmaleficence and beneficence while maintaining a higher priority on the former.

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Dose effect relationship and estimation of the carcinogenic effects of low doses of ionising radiation: the Joint Report of the Academie des Sciences (Paris) and of the Academie Nationale de Medecine

Cited by 54 publications

References 9 publications

A brief review of radiation hormesis

A brief review of radiation hormesis

Murine Microenvironment Metaprofiles Associate with Human Cancer Etiology and Intrinsic Subtypes

The hormesis concept and risk assessment: are there unique ethical and policy considerations?

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