Induction of Single-and Double-Strand Breaks in Plasmid DNA by Monoenergetic Alpha-Particles with Energies below the Bragg-Maximum

Scholz, Volker; Weidner, Jürgen; Köhnlein, W.; Frekers, D.; Wörtche, H. J.

doi:10.1515/znc-1997-5-615

Cited by 3 publications

(3 citation statements)

References 6 publications

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“…Increase in p53 protein by ionizing radiation that is independent of transcription can be due to activation of the DNA damage response pathway. Ionizing radiation induces more of the deleterious DNA DSBs than single strand breaks [40]. …”

Section: Resultsmentioning

confidence: 99%

Radiation Induced Apoptosis of Murine Bone Marrow Cells Is Independent of Early Growth Response 1 (EGR1)

et al. 2017

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An understanding of how each individual 5q chromosome critical deleted region (CDR) gene contributes to malignant transformation would foster the development of much needed targeted therapies for the treatment of therapy related myeloid neoplasms (t-MNs). Early Growth Response 1 (EGR1) is a key transcriptional regulator of myeloid differentiation located within the 5q chromosome CDR that has been shown to regulate HSC (hematopoietic stem cell) quiescence as well as the master regulator of apoptosis—p53. Since resistance to apoptosis is a hallmark of malignant transformation, we investigated the role of EGR1 in apoptosis of bone marrow cells; a cell population from which myeloid malignancies arise. We evaluated radiation induced apoptosis of Egr1+/+ and Egr1-/- bone marrow cells in vitro and in vivo. EGR1 is not required for radiation induced apoptosis of murine bone marrow cells. Neither p53 mRNA (messenger RNA) nor protein expression is regulated by EGR1 in these cells. Radiation induced apoptosis of bone marrow cells by double strand DNA breaks induced p53 activation. These results suggest EGR1 dependent signaling mechanisms do not contribute to aberrant apoptosis of malignant cells in myeloid malignancies.

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Section: Resultsmentioning

confidence: 99%

Radiation Induced Apoptosis of Murine Bone Marrow Cells Is Independent of Early Growth Response 1 (EGR1)

et al. 2017

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“… 15 The interaction of high LET ionizing radiation with DNA molecules produces localized regions with a high density of DNA damage. 102 High LET ions interact with a high atomic number (Z) NP via Coulomb collisions. The cross‐section depends on the kinetic energy and charge of the incident particle and the impact parameter (radial distance from the particle's track to the target).…”

Section: Let (Linear Energy Transfer) Of the Radiationmentioning

confidence: 99%

“…DNA damages induced by NPs is amplified more strongly at the end of the particle track 15 . The interaction of high LET ionizing radiation with DNA molecules produces localized regions with a high density of DNA damage 102 . High LET ions interact with a high atomic number (Z) NP via Coulomb collisions.…”

Section: Let (Linear Energy Transfer) Of the Radiationmentioning

confidence: 99%

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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Nanodosimetric Simulation of Direct Ion-Induced DNA Damage Using Different Chromatin Geometry Models

et al. 2017

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Monte Carlo based simulation has proven useful in investigating the effect of proton-induced DNA damage and the processes through which this damage occurs. Clustering of ionizations within a small volume can be related to DNA damage through the principles of nanodosimetry. For simulation, it is standard to construct a small volume of water and determine spatial clusters. More recently, realistic DNA geometries have been used, tracking energy depositions within DNA backbone volumes. Traditionally a chromatin fiber is built within the simulation and identically replicated throughout a cell nucleus, representing the cell in interphase. However, the in vivo geometry of the chromatin fiber is still unknown within the literature, with many proposed models. In this work, the Geant4-DNA toolkit was used to build three chromatin models: the solenoid, zig-zag and cross-linked geometries. All fibers were built to the same chromatin density of 4.2 nucleosomes/11 nm. The fibers were then irradiated with protons (LET 5-80 keV/μm) or alpha particles (LET 63-226 keV/μm). Nanodosimetric parameters were scored for each fiber after each LET and used as a comparator among the models. Statistically significant differences were observed in the double-strand break backbone size distributions among the models, although nonsignificant differences were noted among the nanodosimetric parameters. From the data presented in this article, we conclude that selection of the solenoid, zig-zag or cross-linked chromatin model does not significantly affect the calculated nanodosimetric parameters. This allows for a simulation-based cell model to make use of any of these chromatin models for the scoring of direct ion-induced DNA damage.

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Induction of Single-and Double-Strand Breaks in Plasmid DNA by Monoenergetic Alpha-Particles with Energies below the Bragg-Maximum

Cited by 3 publications

References 6 publications

Radiation Induced Apoptosis of Murine Bone Marrow Cells Is Independent of Early Growth Response 1 (EGR1)

Radiation Induced Apoptosis of Murine Bone Marrow Cells Is Independent of Early Growth Response 1 (EGR1)

Nanoscopic biodosimetry using plasmid DNA in radiotherapy with metallic nanoparticles

Nanodosimetric Simulation of Direct Ion-Induced DNA Damage Using Different Chromatin Geometry Models

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