Evaluation of lesion clustering in irradiated plasmid DNA

Leloup, Corinne; Garty, Guy; Assaf, Gad; Cristovão, A; Breskin, A.; Chechik, R.; Shchemelinin, S.; Paz-Elizur, Tamar; Livneh, Zvi; Schulte, R.; Bashkirov, V.; Milligan, Jamie R.; Großwendt, B.

doi:10.1080/09553000400017895

Cited by 92 publications

(92 citation statements)

References 52 publications

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“…This result could be considered to be associated with these factors, such as the type of DNA (DNA sequence), the buffer solution surrounding of DNA, radiation dose, and different LET of γ-rays used, As the frequency of DNA DSB production is so low and almost can not be detected, a slight underestimation could also be possible than the level of real ones, depending on the dose. The DSB and non-DSB cluster yields for protons radiation, in present study, show the same order as those reported by Leloup et al [19]. In Leloup's study, the pHAZE DNA irradiation was conducted in the radioquenching solution (200 mmol/L glycerol).…”

Section: Resultssupporting

confidence: 74%

“…To our knowledge, although there are series of research reports regarding the efficiencies of DSBs and non-DSB clustered DNA damage induction by high or low LET radiation [7−18], very few experimental studies were conducted on the comparison of protons with heavy ions or low LET radiation. In a former report, the energy of protons and the buffer solution surrounding of DNA used is different [19], so the disaccord about yields of clustered DNA damage exist. In experiment of Leloup et al [19], pHAZE plasmid DNA was irradiated with 1.03, 19.3 and 249 MeV protons (LET=25.5, 2.7 and 0.39 keV/μm respectively) in phosphate buffer containing 2 mmol/L or 200 mmol/L glycerol, the results have shown that single-strand breaks (SSBs) yield decreased with increasing LET, the yield of DSB and all clustered lesions seemed to reach a minimum around 3 keV/μm.…”

mentioning

confidence: 99%

“…In a former report, the energy of protons and the buffer solution surrounding of DNA used is different [19], so the disaccord about yields of clustered DNA damage exist. In experiment of Leloup et al [19], pHAZE plasmid DNA was irradiated with 1.03, 19.3 and 249 MeV protons (LET=25.5, 2.7 and 0.39 keV/μm respectively) in phosphate buffer containing 2 mmol/L or 200 mmol/L glycerol, the results have shown that single-strand breaks (SSBs) yield decreased with increasing LET, the yield of DSB and all clustered lesions seemed to reach a minimum around 3 keV/μm. There was a higher yield of SSB, DSB and total clustered lesions for DNA in 2 mmol/L glycerol compared to that in 200 mmol/L glycerol, which is similar to the data of Sutherland et al [20].…”

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confidence: 99%

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Clustered DNA damage induced by protons radiation in plasmid DNA

et al. 2013

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Clustered DNA damage is considered as a critical type of lesions induced by ionizing radiation, which can be converted into the fatal or strong mutagenic complex double strand breaks (DSBs) during damage processing in the cells. The new data show that high energy protons produce more potentially lethal DSBs than low LET radiation. In this study, plasmid DNA were used to investigate and re-evaluate the biological effects induced by the protons with the LET of ~3.6 keV/μm at the molecular level in vitro, including single strand breaks (SSBs), DSBs, isolated and clustered base damages. The results of complex DNA damage detections indicated that protons at the given LET value induce about 1.6 fold more non-DSB clustered DNA damages than the prompt DSB. The DNA damage yields by protons were greater than that by γ-rays, specifically by 6 fold for the isolated type of DNA damage and 14 fold for the clustered damage. Furthermore, the spectrum of damages was also demonstrated to be depended on the radiation quality, with protons producing more DSBs relative to clusters than do γ-rays. In the space radiation field, the primary components are galactic cosmic rays (GCR) and solar particle events (SPE). GCR particles consist of 87% protons, 12% alpha particles and about 1% of heavy ions. SPE particles are mainly protons. Among these, protons are obviously the most abundant type of charged particles [1]. Model calculations have suggested that, during transit to Mars, every cell in an astronaut's body would be hit by a proton every few days [2,3]. On earth, worldwide over 40000 cancer patients have received proton radiotherapy [4]. The increasing use of proton radiotherapy necessitates strengthening the study of the basic biological mechanisms associated with exposure to protons. In generally, protons are classified as low linear energy transfer (LET) like the photon from X and γ-rays, that is to say they do not lose much energy when they pass through the matter. DNA is one of the most important targets of ionizing radiation, and the double-strand breakage (DSB) is a particularly hazardous type of DNA damage to dividing cells as it involves a break to both strands nearby in the double helix [5]. The data of Hada and Sutherland [6] indicate that high energy (1 GeV/nucleon, 0.22 keV/μm) protons produce more potentially lethal double-strand breaks (DSBs) than low LET radiation, and the spectrum of damages is very similar to that of high energy iron ions and other heavy charged particles. The distinctive biological mark of heavy ions with high LET is to induce complex DNA damage, including DSBs and non-DSB clustered DNA damage. Clustered lesions are defined as two or more lesions (base damage, single strand break, abasic site) formed within a ~10-bp segment by a single radiation track. Both DSBs and non-DSB clustered DNA damages are considered difficult to be repaired and are closely associated with mutations and cell death. So for re-evaluating the effects of protons on biological systems, it is important to further investigate t...

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Section: Resultssupporting

confidence: 74%

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confidence: 99%

mentioning

confidence: 99%

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Clustered DNA damage induced by protons radiation in plasmid DNA

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“…The unexpected results obtained by Leloup et al [13] show that the yields for SSB and DSB after irradiation with 137 Cs are higher than those obtained after irradiation with 60 Co. The authors suggest that this discrepancy can be due to differences in the spectra of the secondary electrons generated by each gamma.…”

contrasting

confidence: 37%

“…Recently, however, a work comparing the effects of gamma rays from 60 Co and from 137 Cs on plasmid DNA upon in vitro irradiation brought some doubts about the relationship between RBE and the induction of DSB lesions in the DNA molecule [13]. According to these authors, the yield for SSB and DSB induced by gamma rays from 60 Co differs from the corresponding yield induced by gamma rays from 137 Cs for equivalent delivered doses.…”

mentioning

confidence: 83%

In Vitro Effects of Gamma Radiation from 60Co and 137Cs on Plasmid DNA

et al. 2007

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The effects of gamma radiation from 60 Co and 137 Cs on DNA in aqueous solution are studied experimentally. Using an improved plasmid purification protocol and improved electrophoretic gel analysis techniques provided results with relatively small uncertainties. The results are compared with both theoretical and experimental results. In particular, the results obtained here are discussed in the light of recent discussion on supposed differences of the effects induced by gamma radiation from 60 Co and 137 Cs. We find that the effects of both types of gamma radiation are similar.Keywords Double-strand breaks . Single-strand breaks . Scavenger-derived radicals . Ionizing radiation . pBSKS + DNA . Gamma effects Irradiation of purified DNA molecules has been extensively used during the last decades for studying the interaction of ionizing radiation with DNA [1-13]. The results obtained in such in vitro experiments are, in many aspects, in qualitative agreement with those from irradiation of cells and tissues. For instance, the increase of cell apoptosis as a function of the delivered dose resembles, qualitatively, the increase of SSB (single strand break) and J Biol Phys (2007) 33:155-160

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Nanoscopic biodosimetry using plasmid DNA in radiotherapy with metallic nanoparticles

Mansouri

Mesbahi

Hejazi

et al. 2022

J Applied Clin Med Phys

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Nanoscopic lesions (complex damages), are the most lethal lesions for the cells. As nanoparticles have become increasingly popular in radiation therapy and the importance of analyzing nanoscopic dose enhancement has increased, a reliable tool for nanodosimetry has become indispensable. In this regard, the DNA plasmid is a widely used tool as a nanodosimetry probe in radiobiology and nano‐radiosensitization studies. This approach is helpful for unraveling the radiosensitization role of nanoparticles in terms of physical and physicochemical effects and for quantifying radiation‐induced biological damage. This review discusses the potential of using plasmid DNA assays for assessing the relative effects of nano‐radiosensitizers, which can provide a theoretical basis for the development of nanoscopic biodosimetry and nanoparticle‐based radiotherapy.

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Evaluation of lesion clustering in irradiated plasmid DNA

Cited by 92 publications

References 52 publications

Clustered DNA damage induced by protons radiation in plasmid DNA

Clustered DNA damage induced by protons radiation in plasmid DNA

In Vitro Effects of Gamma Radiation from 60Co and 137Cs on Plasmid DNA

Nanoscopic biodosimetry using plasmid DNA in radiotherapy with metallic nanoparticles

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