Assessing cancer risks of low-dose radiation

Mullenders, Leon H.F.; Atkinson, Michael J.; Paretzke, H. G.; Sabatier, Laure; Bouffler, Simon

doi:10.1038/nrc2677

Cited by 181 publications

(123 citation statements)

References 106 publications

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“…Because the extension of the penumbra increases with particle velocity, tissues exposed to very high-energy ions, such as those in space or used in therapy, will experience hotspots of high doses and large volumes with low dose exposure. Controversy surrounding the effects of low doses persists (2,47,48), but our results support the view that every exposure to charged particles should be considered a 3D entanglement of high-dose and low-dose DNA damage induction in tissues.…”

Section: Discussionsupporting

confidence: 70%

Direct measurement of the 3-dimensional DNA lesion distribution induced by energetic charged particles in a mouse model tissue

Mirsch

Tommasino

Frohns

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Charged particles are increasingly used in cancer radiotherapy and contribute significantly to the natural radiation risk. The difference in the biological effects of high-energy charged particles compared with X-rays or γ-rays is determined largely by the spatial distribution of their energy deposition events. Part of the energy is deposited in a densely ionizing manner in the inner part of the track, with the remainder spread out more sparsely over the outer track region. Our knowledge about the dose distribution is derived solely from modeling approaches and physical measurements in inorganic material. Here we exploited the exceptional sensitivity of γH2AX foci technology and quantified the spatial distribution of DNA lesions induced by charged particles in a mouse model tissue. We observed that charged particles damage tissue nonhomogenously, with single cells receiving high doses and many other cells exposed to isolated damage resulting from high-energy secondary electrons. Using calibration experiments, we transformed the 3D lesion distribution into a dose distribution and compared it with predictions from modeling approaches. We obtained a radial dose distribution with sub-micrometer resolution that decreased with increasing distance to the particle path following a 1/r 2 dependency. The analysis further revealed the existence of a background dose at larger distances from the particle path arising from overlapping dose deposition events from independent particles. Our study provides, to our knowledge, the first quantification of the spatial dose distribution of charged particles in biologically relevant material, and will serve as a benchmark for biophysical models that predict the biological effects of these particles.C harged particles, including protons, α-particles, and heavy ions, are increasingly used in cancer radiotherapy and represent a significant component of the natural background irradiation on earth and in space (1-3). Their biological effect is often very different from that of photons (X-or γ-rays), largely because charged particles deposit their energy along a track, whereas photons produce a fairly homogeneous dose distribution. Linear energy transfer (LET; typically given in units of keV/μm) has been introduced as a parameter to describe the amount of energy that charged particles deposit along their track. Particles with high LET are densely ionizing and typically biologically more effective than photons or low-LET particles. Energy deposition along a particle track is not restricted to the path itself (the so-called "track core"), but extends laterally into an area known as the penumbra of the particle, which can reach considerable distances for high-energy particles. Energy deposition in the penumbra arises from energetic secondary electrons, so-called δ-electrons, which are generated by ionization events of the charged particles and carry energy away from the immediate path into the penumbra. According to classical track structure theory, ∼50% of the total energy is deposited in the...

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Section: Discussionsupporting

confidence: 70%

Direct measurement of the 3-dimensional DNA lesion distribution induced by energetic charged particles in a mouse model tissue

Mirsch

Tommasino

Frohns

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…7,8 While many factors may influence the cellular response to low-dose radiation exposure, our studies demonstrated that the environmental oxygen concentration is an element of critical importance. Considering the fact that the principle mode of IR action is through induction of ROS, 9 it is not surprising that the effects of low-dose IR, mediated by a moderate level of ROS, can be profoundly affected by oxygen concentration.…”

Section: Discussionmentioning

confidence: 78%

“…Since the direct biological consequences of low-dose irradiation are relatively subtle and difficult to measure, 7,8 we opted to study the radioadaptive response model to investigate the effects of low-dose radiation because animal studies have demonstrated such adaptive response. 6 We define doses at or below 0.1 Gy as low-dose radiation, 7 equivalent to the upper limit dose from a full-body spiral CT scan 8 and 2-4 Gy as high-dose radiation that causes substantial DNA damage to cells, 9,23 4 Gy is close to the LD50 for human whole-body exposure.…”

Section: Resultsmentioning

confidence: 99%

“…6 Hence, many have argued that the use of the LNT model has led to unfounded levels of public fear regarding low levels of radiation exposure, and misunderstandings about the safety of diagnostic imaging for medical use. 1 However, the controversy remains unresolved due to a lack of understanding of the molecular mechanisms underlying the adaptive stress response, 7,8 and there is insufficient scientific evidence to warrant a change from the LNT model.…”

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confidence: 99%

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Low-dose radiation exposure induces a HIF-1-mediated adaptive and protective metabolic response

et al. 2014

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Because of insufficient understanding of the molecular effects of low levels of radiation exposure, there is a great uncertainty regarding its health risks. We report here that treatment of normal human cells with low-dose radiation induces a metabolic shift from oxidative phosphorylation to aerobic glycolysis resulting in increased radiation resistance. This metabolic change is highlighted by upregulation of genes encoding glucose transporters and enzymes of glycolysis and the oxidative pentose phosphate pathway, concomitant with downregulation of mitochondrial genes, with corresponding changes in metabolic flux through these pathways. Mechanistically, the metabolic reprogramming depends on HIF1a, which is induced specifically by lowdose irradiation linking the metabolic pathway with cellular radiation dose response. Increased glucose flux and radiation resistance from low-dose irradiation are also observed systemically in mice. This highly sensitive metabolic response to lowdose radiation has important implications in understanding and assessing the health risks of radiation exposure.

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“…However, the risk of cancer due to the prolonged low-dose radiation exposure has not been proven consistently. This may be contributed by several factors: individualization of radiation dose is difficult, the background radiation is omnipresent, the radiation-induced cancers are biologically indistinguishable from other extrinsic/intrinsic cancers, the risk of intrinsic cancer is high relative to low projected risk of radiation-induced cancer, and appropriate observational number of the subjects with cancers related to low-dose radiation is difficult (Brenner et al, 2003;Mullenders et al, 2009). Nevertheless, excess relative risks for cancers have been reported among workers in the nuclear power Mao-Chin Hung 1 *, Jeng-Jong Hwang 2 plants and residents in the radiocontaminated buildings.…”

Section: Introductionmentioning

confidence: 99%

Cancer Risk from Medical Radiation Procedures for Coronary Artery Disease: A Nationwide Population-based Cohort Study

Hung

Hwang²

2013

Asian Pacific Journal of Cancer Prevention

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To assess the risk of cancer incidence after medical radiation exposure for coronary artery disease (CAD), a retrospective cohort study was conducted based on Taiwan's National Health Insurance Research Database (NHIRD). Patients with CAD were identified according to the International Classification of Diseases code, 9th Revision, Clinical Modification (ICD-9-CM), and their records of medical radiation procedures were collected from 1997 to 2010. A total of 18,697 subjects with radiation exposure from cardiac imaging or therapeutic procedures for CAD were enrolled, and 19,109 subjects receiving cardiac diagnostic procedures without radiation were adopted as the control group. The distributions of age and gender were similar between the two populations. Cancer risks were evaluated by age-adjusted incidence rate ratio (aIRR) and association with cumulative exposure were further evaluated with relative risks by Poisson regression analysis. A total of 954 and 885 subjects with various types of cancers in both cohorts after following up for over 10 years were found, with incidences of 409.8 and 388.0 per 100,000 person-years, respectively. The risk of breast cancer (aIRR=1.85, 95% confidence interval: 1.14-3.00) was significantly elevated in the exposed female subjects, but no significant cancer risk was found in the exposed males. In addition, cancer risks of the breast and lung were increased with the exposure level. The study suggests that radiation exposure from cardiac imaging or therapeutic procedures for CAD may be associated with the increased risk of breast and lung cancers in CAD patients.Keywords: Coronary artery disease (CAD) -cardiac imaging -cancer risk -incidence rate ratio (IRR)

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Assessing cancer risks of low-dose radiation

Cited by 181 publications

References 106 publications

Direct measurement of the 3-dimensional DNA lesion distribution induced by energetic charged particles in a mouse model tissue

Direct measurement of the 3-dimensional DNA lesion distribution induced by energetic charged particles in a mouse model tissue

Low-dose radiation exposure induces a HIF-1-mediated adaptive and protective metabolic response

Cancer Risk from Medical Radiation Procedures for Coronary Artery Disease: A Nationwide Population-based Cohort Study

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