Mechanisms of induction and repair of DNA double-strand breaks by ionizing radiation: Some contradictions

Hagen, U.

doi:10.1007/bf01255273

Cited by 35 publications

(15 citation statements)

References 108 publications

(103 reference statements)

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“…The problem can also be approached with experimental investigations of the DNA damages and their repairability (Hagen 1994). For example, it has now been shown that DSB rejoining in cells is less after high-LET than after low-LET irradiation (Jenner et al 1993), and that the probability of a DSB leading to cell inactivation is highly dependent on the DSB-inducing agent, being greatest for high-LET radiation, much less for low-LET and much less again for hydrogen peroxide (Prise 1994).…”

Section: Severity Of Clustered Lesionsmentioning

confidence: 99%

Molecular and cell models of biological effects of heavy ion radiation

Goodhead

1995

Radiat Environ Biophys

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Many quantitative models have been developed for the biological effectiveness of radiation of different quality. They differ substantially in their assumptions, and a lack of firm knowledge remains as to the detailed nature of the critical early molecular damage. Analyses of microscopic features of the stochastic structures of radiation tracks have led to hypotheses on the importance of clustered damage in DNA and associated molecules. Clustered damage of greater complexity or severity is suggested to be less repairable and therefore to dominate the biological consequences.

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Section: Severity Of Clustered Lesionsmentioning

confidence: 99%

Molecular and cell models of biological effects of heavy ion radiation

Goodhead

1995

Radiat Environ Biophys

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“…High LET irradiation is defined as an irradiation beam consisting of ionized atoms heavier than helium. It has been proposed that high LET irradiation produces predominantly DSBs, while low LET radiation, X-rays and g-rays, mainly produces DNA single-strand breaks and oxidative damage (Hagen 1994;Goodhead 1995). High LET irradiation has been generally accepted as an effective therapy for cancer, and mutagenesis using heavy-ion beams has become a useful tool for plant and crop breeding (Jones 2006;Tanaka et al 2010).…”

Section: Introductionmentioning

confidence: 99%

The type of mutations induced by carbon-ion-beam irradiation of the filamentous fungus Neurospora crassa

Kazama

Inoue

et al. 2013

Fungal Biology

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“…Many different definitions of clustered damage -together with interpretations of the mechanisms determining its biological relevance -can be found in the literature [2][3][4][5][6]. A major problem related to such interpretations is the lack of clear experimental results on what a doublestrand break (dsb) or a clustered lesion really is [7], thus making the definition of a one-to-one relationship between what is modelled and what is measured problematic.…”

Section: Introductionmentioning

confidence: 99%

DNA complex lesions induced by protons and ⋅ -particles: track structure characteristics determining linear energy transfer and particle type dependence

Ottolenghi

Merzagora

Paretzke

1997

Radiation and Environmental Biophysics

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The yield of DNA double-strand breaks (dsb) and DNA complex lesions induced by protons and alpha-particles of various energies was simulated using a Monte Carlo track structure code (MOCA15) and a simple model of the DNA molecule. DNA breaks of different complexity were analysed. The linear energy transfer (LET) and particle-type dependence of lesions of higher complexity seems to confirm the importance of clustered damage in DNA as a relevant step leading to biological endpoints such as cell inactivation. The detailed structure of proton and alpha-particle tracks was analysed to identify the main characteristics possibly responsible for such a dependence. The role of the primary ion and of its secondary electrons in inducing dsb and complex lesions is described, showing that the relative contribution of secondary electron tracks alone in inducing clustered lesions is almost negligible at high LET, but tends to dominate below = 10 keV/micron. This is consistent with the observed similar effectiveness of low-LET fast particle radiation and sparsely ionizing radiation such as x-rays. The dependence on LET and particle type is mainly due to energy deposition events of the primary ion together with short range electrons surrounding the ion track; the yield of complex lesions due to secondary electron tracks alone is substantially LET independent. The radial distributions of the energy contributing to the induction of complex lesions were analyzed and compared with the radial distributions of energy deposition of the full tracks. The results suggest that the stochastic behaviour (i.e. cluster properties) of the energy deposition pattern within a radius of a few nanometers around the ion track plays a relevant role in determining the biological radiation effectiveness.

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Mechanisms of induction and repair of DNA double-strand breaks by ionizing radiation: Some contradictions

Cited by 35 publications

References 108 publications

Molecular and cell models of biological effects of heavy ion radiation

Molecular and cell models of biological effects of heavy ion radiation

The type of mutations induced by carbon-ion-beam irradiation of the filamentous fungus Neurospora crassa

DNA complex lesions induced by protons and ⋅ -particles: track structure characteristics determining linear energy transfer and particle type dependence

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