Heavy-ion induced chromosomal aberrations: A review

Ritter, S.; Durante, Marco

doi:10.1016/j.mrgentox.2010.04.007

Cited by 77 publications

(47 citation statements)

References 79 publications

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“…15 For hadrontherapy, comparison of chromosomal aberrations in peripheral blood lymphocytes of patients treated either with C-ions or X-rays for similar tumours generally shows a higher damage after conventional radiotherapy compared with heavy ion treatment, both for passive modulation 109 and active raster scanning. 110 These results, apparently in contradiction with the increased effectiveness of heavy ions in the induction of chromosomal aberrations, 111 are caused by the different treatment planning. With heavy ions, the integral dose is reduced because, thanks to the Bragg peak, only a few fields (1-3) at different angles are used compared with conformal and intensitymodulated therapy with X-rays (up to 9-10 fields).…”

Section: Late Effectsmentioning

confidence: 98%

New challenges in high-energy particle radiobiology

Durante

2014

BJR

125

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Densely ionizing radiation has always been a main topic in radiobiology. In fact, a-particles and neutrons are sources of radiation exposure for the general population and workers in nuclear power plants. More recently, high-energy protons and heavy ions attracted a large interest for two applications: hadrontherapy in oncology and space radiation protection in manned space missions. For many years, studies concentrated on measurements of the relative biological effectiveness (RBE) of the energetic particles for different end points, especially cell killing (for radiotherapy) and carcinogenesis (for late effects). Although more recently, it has been shown that densely ionizing radiation elicits signalling pathways quite distinct from those involved in the cell and tissue response to photons. The response of the microenvironment to charged particles is therefore under scrutiny, and both the damage in the target and non-target tissues are relevant. The role of individual susceptibility in therapy and risk is obviously a major topic in radiation research in general, and for ion radiobiology as well. Particle radiobiology is therefore now entering into a new phase, where beyond RBE, the tissue response is considered. These results may open new applications for both cancer therapy and protection in deep space.Biological effects of densely ionizing radiation have been studied since the beginning of radiobiology. As a matter of fact, a-particles deliver the main contribution to the background radiation dose on Earth, owing to inhalation of the indoor radon.1 Neutrons have also been extensively studied because of protection of workers in nuclear power plants; use of fast neutrons in radiotherapy; and of the exposure of the survivors of the atomic bomb in Hiroshima and Nagasaki, where a neutron component was added to g-rays. Bacq and Alexander 2 already elegantly described the radiobiology of a-particles and neutrons in their 1955 seminal book.More recently, radiobiology research has focused on highenergy protons and heavy ions, mostly for two reasons: charged particle therapy (CPT) in oncology and radiation protection in manned space missions. In both cases, charged particles at energies .100 MeV n 21 are involved. The characteristic depth-dose distribution with the sharp Bragg peak at the end of the range can be exploited for killing tumours; on the other hand, densely ionizing radiation can effectively delay tissue morbidity. Notwithstanding the many differences in exposure conditions, CPT and space radiation protection share several research topics, including individual sensitivity, non-targeted effects, late stochastic effects and so forth.3 Research in these fields requires large high-energy accelerators and is often performed by the same research groups with a common interest in particle radiobiology. Research is rapidly moving forward owing to the diffusion of CPT centres in the USA, Europe, and Asia 4 and to the growing interest in manned space exploration, now a priority for all space agencies, 5 but wi...

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Section: Late Effectsmentioning

confidence: 98%

New challenges in high-energy particle radiobiology

Durante

2014

BJR

125

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“…In other words, it takes 40 times more dose of X-rays to lead to the same tumor incidence than with HZE Fe. In contrast, in vitro studies for mammalian cell survival have led to much lower RBE with values ~2 for primary human breast epithelial cell survival exposed to 1 GeV/n Fe [4] or between 2 to 10 for chromosomal aberrations for various HZE [5]. There are therefore discrepancies between in vitro and in vivo responses, and mechanistic models may help resolve such discrepancies.…”

Section: Introductionmentioning

confidence: 98%

Combinatorial DNA Damage Pairing Model Based on X-Ray-Induced Foci Predicts the Dose and LET Dependence of Cell Death in Human Breast Cells

et al. 2014

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In contrast to the classic view of static DNA double strand breaks (DSBs) being repaired at the site of damage, we hypothesize that DSBs move and merge with each other over large distances (µm). As X-ray dose increases, the probability of having DSB clusters increases and so does the probability of misrepair and cell death. Experimental work characterizing the dose dependence of radiation-induced foci (RIF) from X-ray in nonmalignant human mammary epithelial cells (MCF10A) is used here to validate a DSB clustering model. We then use the principles of the local effect model (LEM) to predict the yield of DSB at the sub-micron level. Two mechanisms for DSB clustering are first compared: random coalescence of DSBs versus active movement of DSBs into repair domains. Simulations that best predict both RIF dose dependence and cell survival following X-ray favor the repair domain hypothesis, suggesting the nucleus is divided into an array of regularly spaced repair domains of ~1.55 µm sides. Applying the same approach to high-LET ion tracks, we can predict experimental RIF/µm along tracks with an overall relative error of 12%, for LET ranging between 30 and 350 keV/µm and for three different ions. Finally, cell death is predicted by assuming an exponential dependence on the total number of DSBs and of all possible combinations of paired DSBs within each simulated RIF. RBE predictions for cell survival of MCF10A exposed to high-LET show an LET dependence that matches previous experimental results for similar cell types. Overall, this work suggests that microdosimetric properties of ion tracks at the sub-micron level are sufficient to explain both RIF data and survival curves for any LET, similarly to the LEM assumption. On the other hand, high-LET death mechanism does not have to infer linear-quadratic dose formalism as done in the LEM. In addition, the size of repair domains derived in our model are based on experimental RIF and are three times larger than the hypothetical LEM voxel used to fit survival curves. Our model is therefore an alternative to previous approaches by providing a testable biological mechanism (i.e. RIF). More generally, DSB pairing will help develop more accurate alternatives to the simplistic linear cancer risk model (LNT) currently used for regulating exposure to very low levels of ionizing radiation.Vadhavkar et al.

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“…In plants, the biological effects of heavy-ion radiation encompassed a wide range of alterations, including developmental abnormalities (Kranz, 1994), chromosomal aberrations (Ritter & Durante, 2010;Kikuchi et al, 2009;Wei et al, 2006) and increased mutation rates (Du et al, 2014). Heavy-ion radiation-induced variations have also been found in the plant genome (Xu et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Brief Overview of Sweet Sorghum Irradiated by Carbon Ion Beam

Dong¹,

Li²,

Liu³

et al. 2017

JAS

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Sweet sorghum [Sorghum bicolor (L.) Moench] is a C 4 plant characterized by a high photosynthetic efficiency and a high biomass-and sugar-yielding crop. However, the current varieties of sweet sorghum cannot meet the rapid growth demand for bio-ethanol production because of its low sugar content in China. To breed novel varieties to provide excellent raw materials for bio-ethanol production, the dry seeds were irradiated by carbon ion beam irradiation with different doses in sweet sorghum, resulting in acquiring an early-maturity mutant at 80 Gy dose, which the growth period was stably shortened for around 20 days compared to wild-type plant. In this paper, we briefly summarized the biological effects induced by carbon ion beam, the characters of early-maturity mutant, and revealed corresponding mechanisms from the point of view of morphological, physiological and molecular levels. In conclusion, there were significant effects on sweet sorghum irradiated by carbon ion beam.

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Heavy-ion induced chromosomal aberrations: A review

Cited by 77 publications

References 79 publications

New challenges in high-energy particle radiobiology

New challenges in high-energy particle radiobiology

Combinatorial DNA Damage Pairing Model Based on X-Ray-Induced Foci Predicts the Dose and LET Dependence of Cell Death in Human Breast Cells

Brief Overview of Sweet Sorghum Irradiated by Carbon Ion Beam

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