Proton irradiation induced reactive oxygen species promote morphological and functional changes in HepG2 cells

Răileanu, Mina; Straticiuc, M.; Iancu, Decebal-Alexandru; Andrei, Radu-Florin; Mihai, Radu; Bacalum, Mihaela

doi:10.1016/j.jsb.2022.107919

Cited by 3 publications

(3 citation statements)

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“…In agreement with our previous findings (33) and the literature (50,51), this pan-nuclear γH2AX signal is not linked to the induction of apoptosis (71) nor to the presence of DSBs, since, like others (50,51), we do not find 53BP1 accumulation outside the localized irradiation sites. This pan-nuclear γH2AX is likely due to a stress signal resulting from an increase in indirect DNA lesions induced by reactive species, and/or increase in the complexity or clustering of DNA damage generated by charged particle-irradiation (50,51,64,70). Nevertheless, although this γH2AX signal does not correspond to high LET IR-induced DSBs, it still directly correlates with the number of charged particles delivered during irradiation and its disappearance with the repair of DNA lesions induced by protons or α-particles.…”

Section: Discussionmentioning

confidence: 99%

“…There are multiple studies pointing out that irradiations with different types of particles (i.e., species, energy and linear energy transfer (LET) of particles) induce different kinds of DNA damage (64,65) with different levels of complexity (i.e., different types of DNA lesions in the same DNA region) and clustering (i.e., accumulation of DNA damage in the same DNA region) (66,67). Apart from DNA lesions directly induced by direct interaction with the DNA molecule, ionizing radiation (IR) also creates reactive species (i.e., reactive oxygen or nitrogen species, ROS or RNS) by interacting with other molecules, such as water, proteins, etc… (68)(69)(70), which then also contribute to further formation of DNA damage within irradiated cells. Computational approaches (66,67) showed that irradiations with α-particles lead to a small number of DNA damage sites with concentrated clusters of complex DNA lesions compared to irradiations with protons, which give a higher number of DNA damage sites containing less clusters of complex DNA lesions.…”

Section: Hr Is Implicated Sooner In the Processing Of Dna Lesions Ind...mentioning

confidence: 99%

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The DNA damage response relies on the characteristics of ionizing particles in myogenic cells

Sutcu,

Thomas--Joyeux,

Cardot-Martin

et al. 2024

Preprint

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DNA integrity and stability are vital for proper cellular activity. Nevertheless, to treat cancer patients, DNA is the main target for inducing tumoral cell death. Nowadays, cancer treatment is improving by the development of new technologies, protocols and strategies. Amongst them, the introduction of charged particles as a form of radiotherapy is underway. However, tumor-neighboring healthy tissues are still exposed to ionizing radiations (IR) and subject to late side effects. Skeletal muscle is one of those tissues most likely to be affected. To decipher the DNA damage response (DDR) of skeletal muscle cells, myogenic cells, we irradiated them with microbeams of protons or α-particles and followed the accumulation of DDR proteins at irradiation sites. Thereby, we showed that myoblasts, proliferating myogenic cells, repair IR-induced DNA damage through both non-homologous end-joining and homologous recombination with different recruitment dynamics depending on the characteristics of ionizing particles (type, energy deposition and time after irradiation), whereas myotubes, post-mitotic myogenic cells, display reduced DNA damage response.SummaryMouse skeletal muscle cells and their precursor cells irradiated by ion microbeam show DNA damage response and DNA repair dynamics that vary according to the characteristics of ionizing particles delivered.Graphical Abstract

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Section: Discussionmentioning

confidence: 99%

Section: Hr Is Implicated Sooner In the Processing Of Dna Lesions Ind...mentioning

confidence: 99%

The DNA damage response relies on the characteristics of ionizing particles in myogenic cells

Sutcu,

Thomas--Joyeux,

Cardot-Martin

et al. 2024

Preprint

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“…Терапевтический эффект ПТ состоит в стойком повреждении генетического материала опухолевых клеток, ведущем к их гибели [6]. При этом цитотоксический эффект протонов обусловлен как прямым повреждением цепи ДНК опухолевых клеток, так и косвенным путем -за счет индукции образования активных форм кислорода [7] и стимуляции апоптоза (за счет активации каспазы-3 протонами) [8].…”

Section: Introductionunclassified

Study of head and neck squamous cell carcinoma transcriptome after proton therapy

Jumaniyazova,

Vishnyakova,

Chirkova

et al. 2024

Bûll. sib. med.

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Aim. To evaluate changes in the transcriptome of head and neck squamous cell carcinoma (HNSCC) tissue cells in patients after proton therapy.Materials and methods. Biopsy material obtained from 3 HNSCC patients before and after proton therapy at a total dose of 10 isoGy was homogenized, purified, and concentrated. Then total RNA was isolated with further purification and concentration with the RNA Clean & Concentrator kit (Zymo Research). Library quantitation was assessed using the Qubit 2.0 instrument (Invitrogen, Life Technologies). After isolation of 1 μg total RNA for sequencing, libraries were prepared on the Illumina platform using the TruSeq RNA Sample Prep Kit v2 with a 10-cycle enrichment step according to the manufacturer’s recommendations. The quality of RNA and the resulting libraries was checked using the Agilent 2100 Bioanalyzer system (Agilent Tec. Inc., USA). The RIN parameter for RNA was at least 7. The library concentration was assessed by real-time PCR on the CFX96 Touch Real-Time PCR Detection System (Bio-Rad, USA). Final libraries were pooled in equimolar ratios before sequencing on the Illumina HiSeq 2500 platform using 50 base-pair paired-end reads. The Q20 parameter for all samples was > 97%, and the number of reads averaged 60.2 million per sample. Raw reads were processed using the RTA 1.17.21.3 and Casava 1.8.2 (Illumina). The enrichment analysis was performed using the PANTHER 17.0 software.Results. The transcriptome analysis of HNSCC after proton radiation therapy (5 x 2 isoGy) at a total dose of 10 isoGy revealed 1,414 significantly differentially expressed genes. The 10 most and least expressed genes and their associated signaling pathways were identified. A number of signaling pathways associated with the underexpressed genes were detected in HNSCC after proton therapy, such as: STAT5; PD-1 signaling pathway; marked MET-mediated activation of PTK2 signaling pathway, PDGF signaling; CD22-mediated regulation of BCR; and FCERI-mediated MAPK activation. In addition to the above signaling pathways, activation of collagen degradation, FCGR3A-mediated phagocytosis, and FCGR3A-mediated interleukin (IL)-10 synthesis are of interest. In the enrichment analysis among highly expressed genes, keratinization and biological oxidation processes were activated in HNSCC tissues after proton therapy.Conclusion. Proton therapy in HNSCC leads to overexpression of genes involved in the regulation of keratinization and biological oxidation processes as well as to underexpression of genes associated with suppression of signaling pathways: STAT5, PD-1, MET-mediated activation of PTK2 signaling pathway, PDGF signaling; CD22-mediated regulation of BCR; FCERI-mediated MAPK activation, collagen degradation, FCGR3A-mediated phagocytosis activation, and FCGR3A-mediated IL-10 synthesis. All signaling pathways of underexpressed genes function in HNSCC cells if there is no negative influence on the tumor from outside (irradiation or delivery of antitumor drugs). The predominance of suppressed signaling pathways over activated ones most likely indicates a decrease in the functional potential of cells after proton therapy. The dose-dependence of PT effects necessitates further study of changes in cellular and molecular-genetic signatures of HNSCC after proton irradiation with different doses.

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Bismuth nanoparticles-enhanced proton therapy: Concept and biological assessment

Zavestovskaya,

Filimonova,

Popov

et al. 2024

Materials Today Nano

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Proton irradiation induced reactive oxygen species promote morphological and functional changes in HepG2 cells

Cited by 3 publications

References 70 publications

The DNA damage response relies on the characteristics of ionizing particles in myogenic cells

The DNA damage response relies on the characteristics of ionizing particles in myogenic cells

Study of head and neck squamous cell carcinoma transcriptome after proton therapy

Bismuth nanoparticles-enhanced proton therapy: Concept and biological assessment

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