scholarly journals From Energy Deposition of Ionizing Radiation to Cell Damage Signaling: Benchmarking Simulations by Measured Yields of Initial DNA Damage after Ion Microbeam Irradiation

2019 ◽  
Vol 191 (6) ◽  
pp. 566 ◽  
Author(s):  
Géraldine Gonon ◽  
Carmen Villagrasa ◽  
Pascale Voisin ◽  
Sylvain Meylan ◽  
Marta Bueno ◽  
...  
Keyword(s):  
Dna Damage ◽  
Ionizing Radiation ◽  
Energy Deposition ◽  
Cell Damage ◽  
Microbeam Irradiation

scholarly journals Integrated Analysis of the Altered lncRNAs and mRNAs Expression in 293T Cells after Ionizing Radiation Exposure

2019 ◽  
Vol 20 (12) ◽  
pp. 2968 ◽  
Author(s):  
Mengmeng Yang ◽  
Yuxiao Sun ◽  
Changyan Xiao ◽  
Kaihua Ji ◽  
Manman Zhang ◽  
...  
Keyword(s):  
Dna Damage ◽  
Ionizing Radiation ◽  
Cell Damage ◽  
Expression Profiles ◽  
Integrated Analysis ◽  
Control Group ◽  
Altered Expression ◽  
Exact Function ◽  
Radiation Induced ◽  
Ionizing Radiation Exposure

Tissue and cell damage caused by ionizing radiation is often highly genotoxic. The swift repair of DNA damage is crucial for the maintenance of genomic stability and normal cell fitness. Long noncoding RNAs (lncRNAs) have been reported to play an important role in many physiological and pathological processes in cells. However, the exact function of lncRNAs in radiation-induced DNA damage has yet to be elucidated. Therefore, this study aimed to analyze the potential role of lncRNAs in radiation-induced DNA damage. We examined the expression profiles of lncRNAs and mRNAs in 293T cells with or without 8 Gy irradiation using high-throughput RNA sequencing. We then performed comprehensive transcriptomic and bioinformatic analyses of these sequencing results. A total of 18,990 lncRNAs and 16,080 mRNAs were detected in all samples. At 24 h post irradiation, 49 lncRNAs and 323 mRNAs were differentially expressed between the irradiation group and the control group. qRT-PCR was used to verify the altered expression of six lncRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses indicated that the predicted genes were mainly involved in the histone mRNA metabolic process and Wnt signaling pathways. This study may provide novel insights for the study of lncRNAs in radiation-induced DNA damage.

scholarly journals A Small Compound KJ-28d Enhances the Sensitivity of Non-Small Cell Lung Cancer to Radio- and Chemotherapy

2019 ◽  
Vol 20 (23) ◽  
pp. 6026
Author(s):  
Hwani Ryu ◽  
Hyo Jeong Kim ◽  
Jie-Young Song ◽  
Sang-Gu Hwang ◽  
Jae-Sung Kim ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Dna Damage ◽  
Ionizing Radiation ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Therapeutic Agent ◽  
Apoptotic Cell ◽  
Combined Treatment ◽  
Small Cell ◽  
Small Cell Lung

We previously reported on a poly (ADP-ribose) polymerase (PARP) 1/2 inhibitor N-(3-(hydroxycarbamoyl)phenyl)carboxamide (designated KJ-28d), which increased the death of human ovarian cancer BRCA1-deficient SNU-251 cells. In the present study, we further investigated the antitumor activities of KJ-28d in BRCA-proficient non-small cell lung cancer (NSCLC) cells to expand the use of PARP inhibitors. KJ-28d significantly inhibited the growth of NSCLC cells in vitro and in vivo, and induced DNA damage and reactive oxygen species in A549 and H1299 cells. Combined treatment with KJ-28d and ionizing radiation led to increased DNA damage responses in A549 and H1299 cells compared to KJ-28d or ionizing radiation alone, resulting in apoptotic cell death. Moreover, the combination of KJ-28d plus a DNA-damaging therapeutic agent (carboplatin, cisplatin, paclitaxel, or doxorubicin) synergistically inhibited cell proliferation, compared to either drug alone. Taken together, the findings demonstrate the potential of KJ-28d as an effective anti-cancer therapeutic agent for BRCA-deficient and -proficient cancer cells. KJ-28d might have potential as an adjuvant when used in combination with radiotherapy or DNA-damaging agents, pending further investigations.

Characterization of DNA damage-induced cellular senescence by ionizing radiation in endothelial cells

2013 ◽  
Vol 90 (1) ◽  
pp. 71-80 ◽  
Author(s):  
Kwang Seok Kim ◽  
Jung Eun Kim ◽  
Kyu Jin Choi ◽  
Sangwoo Bae ◽  
Dong Ho Kim
Keyword(s):  
Dna Damage ◽  
Endothelial Cells ◽  
Ionizing Radiation ◽  
Cellular Senescence

scholarly journals Truncated PPM1D Prevents Apoptosis in the Murine Thymus and Promotes Ionizing Radiation-Induced Lymphoma

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 2068
Author(s):  
Andra S. Martinikova ◽  
Monika Burocziova ◽  
Miroslav Stoyanov ◽  
Libor Macurek
Keyword(s):  
Dna Damage ◽  
Ionizing Radiation ◽  
Tumor Formation ◽  
Cell Cycle Checkpoints ◽  
Negative Regulator ◽  
Tumor Suppressor P53 ◽  
Mouse Thymus ◽  
Truncating Mutation ◽  
T Cell Lymphomas ◽  
Radiation Induced

Genome integrity is protected by the cell-cycle checkpoints that prevent cell proliferation in the presence of DNA damage and allow time for DNA repair. The transient checkpoint arrest together with cellular senescence represent an intrinsic barrier to tumorigenesis. Tumor suppressor p53 is an integral part of the checkpoints and its inactivating mutations promote cancer growth. Protein phosphatase magnesium-dependent 1 (PPM1D) is a negative regulator of p53. Although its loss impairs recovery from the G2 checkpoint and promotes induction of senescence, amplification of the PPM1D locus or gain-of-function truncating mutations of PPM1D occur in various cancers. Here we used a transgenic mouse model carrying a truncating mutation in exon 6 of PPM1D (Ppm1dT). As with human cell lines, we found that the truncated PPM1D was present at high levels in the mouse thymus. Truncated PPM1D did not affect differentiation of T-cells in the thymus but it impaired their response to ionizing radiation (IR). Thymocytes in Ppm1dT/+ mice did not arrest in the checkpoint and continued to proliferate despite the presence of DNA damage. In addition, we observed a decreased level of apoptosis in the thymi of Ppm1dT/+ mice. Moreover, the frequency of the IR-induced T-cell lymphomas increased in Ppm1dT/+Trp53+/− mice resulting in decreased survival. We conclude that truncated PPM1D partially suppresses the p53 pathway in the mouse thymus and potentiates tumor formation under the condition of a partial loss of p53 function.

scholarly journals Differential DNA Damage Response of Peripheral Blood Lymphocyte Populations

2021 ◽  
Vol 12 ◽  
Author(s):  
Kerstin Felgentreff ◽  
Catharina Schuetz ◽  
Ulrich Baumann ◽  
Christian Klemann ◽  
Dorothee Viemann ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Ionizing Radiation ◽  
Dna Damage Response ◽  
Peripheral Blood ◽  
Low Dose ◽  
Lymphocyte Subsets ◽  
Mass Cytometry ◽  
Damage Response ◽  
Lymphocyte Populations

DNA damage occurs constantly in every cell triggered by endogenous processes of replication and metabolism, and external influences such as ionizing radiation and intercalating chemicals. Large sets of proteins are involved in sensing, stabilizing and repairing this damage including control of cell cycle and proliferation. Some of these factors are phosphorylated upon activation and can be used as biomarkers of DNA damage response (DDR) by flow and mass cytometry. Differential survival rates of lymphocyte subsets in response to DNA damage are well established, characterizing NK cells as most resistant and B cells as most sensitive to DNA damage. We investigated DDR to low dose gamma radiation (2Gy) in peripheral blood lymphocytes of 26 healthy donors and 3 patients with ataxia telangiectasia (AT) using mass cytometry. γH2AX, p-CHK2, p-ATM and p53 were analyzed as specific DDR biomarkers for functional readouts of DNA repair efficiency in combination with cell cycle and T, B and NK cell populations characterized by 20 surface markers. We identified significant differences in DDR among lymphocyte populations in healthy individuals. Whereas CD56+CD16+ NK cells showed a strong γH2AX response to low dose ionizing radiation, a reduced response rate could be observed in CD19+CD20+ B cells that was associated with reduced survival. Interestingly, γH2AX induction level correlated inversely with ATM-dependent p-CHK2 and p53 responses. Differential DDR could be further noticed in naïve compared to memory T and B cell subsets, characterized by reduced γH2AX, but increased p53 induction in naïve T cells. In contrast, DDR was abrogated in all lymphocyte populations of AT patients. Our results demonstrate differential DDR capacities in lymphocyte subsets that depend on maturation and correlate inversely with DNA damage-related survival. Importantly, DDR analysis of peripheral blood cells for diagnostic purposes should be stratified to lymphocyte subsets.

Irreversible electron attachment – a key to DNA damage by solvated electrons in aqueous solution

2015 ◽  
Vol 13 (41) ◽  
pp. 10362-10369 ◽  
Author(s):  
K. Westphal ◽  
J. Wiczk ◽  
J. Miloch ◽  
G. Kciuk ◽  
K. Bobrowski ◽  
...  
Keyword(s):  
Aqueous Solution ◽  
Dna Damage ◽  
Ionizing Radiation ◽  
Electron Attachment ◽  
Solvated Electrons ◽  
Radiation Induced

In an aqueous solution trinucleotides labeled with bromonucleobases are damaged by ionizing radiation induced electrons while native trimers are insensitive to electrons under the same conditions.

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