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h2ax and irradiation

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https://www.readbyqxmd.com/read/28327192/dna-double-strand-breaks-in-human-induced-pluripotent-stem-cell-reprogramming-and-long-term-in-vitro-culturing
#1
Pavel Simara, Lenka Tesarova, Daniela Rehakova, Pavel Matula, Stanislav Stejskal, Ales Hampl, Irena Koutna
BACKGROUND: Human induced pluripotent stem cells (hiPSCs) play roles in both disease modelling and regenerative medicine. It is critical that the genomic integrity of the cells remains intact and that the DNA repair systems are fully functional. In this article, we focused on the detection of DNA double-strand breaks (DSBs) by phosphorylated histone H2AX (known as γH2AX) and p53-binding protein 1 (53BP1) in three distinct lines of hiPSCs, their source cells, and one line of human embryonic stem cells (hESCs)...
March 21, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28291710/measurement-of-dna-damage-in-peripheral-blood-by-the-%C3%AE-h2ax-assay-as-predictor-of-colorectal-cancer-risk
#2
Lina Zhao, David W Chang, Yilei Gong, Cathy Eng, Xifeng Wu
The detection of γ-H2AX focus is one of the most sensitive ways to monitor DNA double-strand breaks (DSBs). Although changes in γ-H2AX activity have been studied in tumor cells in colorectal cancer (CRC), changes in peripheral blood lymphocytes (PBLs) have not been examined previously. We hypothesize that higher levels of irradiation-induced γ-H2AX in PBLs may be associated with an elevated risk of colorectal cancer (CRC). In a case-control study, the baseline and ionizing radiation (IR)-induced γ-H2AX levels in PBLs from frequency-matched 320 untreated CRC patients and 320 controls were detected by a laser scanning cytometer-based immunocytochemical method...
March 6, 2017: DNA Repair
https://www.readbyqxmd.com/read/28277539/epidermal-rac1-regulates-the-dna-damage-response-and-protects-from-uv-light-induced-keratinocyte-apoptosis-and-skin-carcinogenesis
#3
Jayesh Deshmukh, Ruth Pofahl, Ingo Haase
Non-melanoma skin cancer (NMSC) is the most common type of cancer. Increased expression and activity of Rac1, a small Rho GTPase, has been shown previously in NMSC and other human cancers; suggesting that Rac1 may function as an oncogene in skin. DMBA/TPA skin carcinogenesis studies in mice have shown that Rac1 is required for chemically induced skin papilloma formation. However, UVB radiation by the sun, which causes DNA damage, is the most relevant cause for NMSC. A potential role of Rac1 in UV-light-induced skin carcinogenesis has not been investigated so far...
March 9, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28267650/toxic-effects-of-56-fe-ion-radiation-on-the-zebrafish-danio-rerio-embryonic-development
#4
Jing Si, Rong Zhou, Jing'e Song, Lu Gan, Xin Zhou, Cuixia Di, Yang Liu, Aihong Mao, Qiuyue Zhao, Yupei Wang, Hong Zhang
All living organisms and ecosystems are permanently exposed to ionizing radiation. Of all the types of ionizing radiation, heavy ions such as (56)Fe have the potential to cause the most severe biological effects. We therefore examined the effects and potential mechanisms of iron ion irradiation on the induction of developmental toxicity and apoptosis in zebrafish embryos. Zebrafish embryos at 4h post-fertilization (hpf) were divided into five groups: a control group; and four groups irradiated with 0.5, 1, 2, and 4Gy radiation, respectively...
February 28, 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/28243358/hydrogen-rich-water-ameliorates-total-body-irradiation-induced-hematopoietic-stem-cell-injury-by-reducing-hydroxyl-radical
#5
Junling Zhang, Xiaolei Xue, Xiaodan Han, Yuan Li, Lu Lu, Deguan Li, Saijun Fan
We examined whether consumption of hydrogen-rich water (HW) could ameliorate hematopoietic stem cell (HSC) injury in mice with total body irradiation (TBI). The results indicated that HW alleviated TBI-induced HSC injury with respect to cell number alteration and to the self-renewal and differentiation of HSCs. HW specifically decreased hydroxyl radical ((∙)OH) levels in the c-kit(+) cells of 4 Gy irradiated mice. Proliferative bone marrow cells (BMCs) increased and apoptotic c-kit(+) cells decreased in irradiated mice uptaken with HW...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28184999/rosiglitazone-enhances-radiosensitivity-by-inhibiting-repair-of-dna-damage-in-cervical-cancer-cells
#6
Zhengzhe An, Jae-Ran Yu, Woo-Yoon Park
Radiation therapy (RT) is one of the main treatment modalities for cervical cancer. Rosiglitazone (ROSI) has been reported to have antiproliferative effects against various types of cancer cells and also to induce antioxidant enzymes that can scavenge reactive oxygen species (ROS) and thereby modify radiosensitivity. Here, we explored the effect of ROSI on radiosensitivity and the underlying mechanisms in cervical cancer cells. Three cervical cancer cell lines (ME-180, HeLa, and SiHa) were used. The cells were pretreated with ROSI and then irradiated...
March 2017: Radiation and Environmental Biophysics
https://www.readbyqxmd.com/read/28178195/overexpression-of-skp2-inhibits-the-radiation-induced-bystander-effects-of-esophageal-carcinoma
#7
Xiao-Chun Wang, Tie-Jun Zhang, Zi-Jian Guo, Chang-Yan Xiao, Xiao-Wen Ding, Fang Fang, Wen-Tao Sheng, Xu Shu, Jue Li
BACKGROUND: To investigate the effects of S-phase kinase protein 2 (SKP2) expression on the radiation induced bystander effect (RIBE) in esophageal cancer (EC) cells. MATERIALS AND METHODS: Western blot was used to detect the levels of SKP2, Rad51, and Ku70 in EC cells. Positive transfection, RNAi, micronucleus (MN), and γ-H2AX focus formation assay were used to investigate the effects of SKP2 on RIBE induced by irradiated cells. RESULTS: We found a significant negative correlation between SKP2 expression and MN frequency (p < 0...
February 6, 2017: International Journal of Environmental Research and Public Health
https://www.readbyqxmd.com/read/28108515/prostate-cancer-patients-with-late-radiation-toxicity-exhibit-reduced-expression-of-genes-involved-in-dna-double-strand-break-repair-and-homologous-recombination
#8
Bregje van Oorschot, Lon Uitterhoeve, Ilja Oomen, Rosemarie Ten Cate, Jan Paul Medema, Harry Vrieling, Lukas J A Stalpers, Perry D Moerland, Nicolaas A P Franken
Severe late damage to normal tissue is a major limitation of cancer radiotherapy in prostate cancer patients. In a recent retrospective study, late radiation toxicity was found to relate to a decreased decay of γ-H2AX foci and reduced induction of DNA double-strand break repair genes. Here, we report evidence of prognostic utility in prostate cancer for γ-H2AX foci decay ratios and gene expression profiles derived from ex vivo-irradiated patient lymphocytes. Patients were followed ≥2 years after radiotherapy...
January 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28107384/an-approach-to-elucidate-nbs1-function-in-dna-repair-using-frequent-nonsynonymous-polymorphism-in-wild-medaka-oryzias-latipes-populations
#9
Kento Igarashi, Junya Kobayashi, Takafumi Katsumura, Yusuke Urushihara, Kyohei Hida, Tomomi Watanabe-Asaka, Hiroki Oota, Shoji Oda, Hiroshi Mitani
Nbs1 is one of the genes responsible for Nijmegen breakage syndrome, which is marked with high radiosensitivity. In human NBS1 (hNBS1), Q185E polymorphism is known as the factor to cancer risks, although its DSB repair defect has not been addressed. Here we investigated the genetic variations in medaka (Oryzias latipes) wild populations, and found 40 nonsynonymous single nucleotide polymorphisms (SNPs) in medaka nbs1 (olnbs1) gene within 5 inbred strains. A mutation to histidine in Q170 residue in olNbs1, which corresponds to Q185 residue of hNBS1, was widely distributed in the closed colonies derived from the eastern Korean population of medaka...
2017: PloS One
https://www.readbyqxmd.com/read/28099140/telomerase-antagonist-imetelstat-increases-radiation-sensitivity-in-esophageal-squamous-cell-carcinoma
#10
Xuping Wu, Jing Zhang, Sijun Yang, Zhihui Kuang, Guolei Tan, Gang Yang, Qichun Wei, Zhigang Guo
The morbidity and mortality of esophageal cancer is one of the highest around the world and the principal therapeutic method is radiation. Thus, searching for sensitizers with lower toxicity and higher efficiency to improve the efficacy of radiation therapy is critical essential. Our research group has previously reported that imetelstat, the thio-phosphoramidate oligonucleotide inhibitor of telomerase, can decrease cell proliferation and colony formation ability as well as increase DNA breaks induced by radiation in esophageal cancer cells...
January 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28062703/tas-116-a-novel-hsp90-inhibitor-selectively-enhances-radiosensitivity-of-human-cancer-cells-to-x-rays-and-carbon-ion-radiation
#11
Younghyun Lee, Shigeaki Sunada, Hirokazu Hirakawa, Akira Fujimori, Jac A Nickoloff, Ryuichi Okayasu
Hsp90 inhibitors have been investigated as cancer therapeutics in monotherapy and to augment radiotherapy; however, serious adverse effects of early-generation Hsp90 inhibitors limited their development. TAS-116 is a novel Hsp90 inhibitor with lower adverse effects than other Hsp90 inhibitors, and here, we investigated the radiosensitizing effects of TAS-116 in low linear energy transfer (LET) X-ray and high LET carbon ion-irradiated human cancer cells and mouse tumor xenografts. TAS-116 decreased cell survival of both X-ray and carbon ion-irradiated human cancer cell lines (HeLa and H1299 cells), and similar to other Hsp90 inhibitors, it did not affect radiosensitivity of noncancerous human fibroblasts...
January 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28052067/the-paradoxical-effects-of-different-hepatitis-c-viral-loads-on-host-dna-damage-and-repair-abilities
#12
Shu-Chi Wang, Kuan-Ru Lai, Chia-Yang Li, Chi-Shiun Chiang, Guann-Yi Yu, Naoya Sakamoto, Wen-Yu Tu, Meng-Hsuan Hsieh, Jee-Fu Huang, Wan-Long Chuang, Chia-Yen Dai, Ming-Lung Yu
Hepatitis C virus (HCV)-induced hepatic stress is associated with increased oxidative DNA damage and has been implicated in hepatic inflammation. However, HCV infection and replication are uneven and vary among individual hepatocytes. To investigate the effect of the viral load on host DNA damage, we used an Enhanced Yellow Fluorescent Protein gene (EYFP)-tagged HCV virus to distinguish between HCV intracellular high viral load (HVL) cells and low viral load (LVL) cells. The cell sorting efficiency was confirmed by the high expression of the HCV polyprotein...
2017: PloS One
https://www.readbyqxmd.com/read/28025714/bone-marrow-mesenchymal-stem-cell-transplantation-improves-radiation-induced-heart-injury-through-dna-damage-repair-in-rat-model
#13
Song Gao, Zhiying Zhao, Rong Wu, Yuecan Zeng, Zhenyong Zhang, Jianing Miao, Zhengwei Yuan
Radiotherapy is an effective form of therapy for most thoracic malignant tumors. However, myocardial injury resulting from the high doses of radiation is a severe complication. Here we aimed to study the possibility of reducing radiation-induced myocardial injury with mesenchymal stem cell (MSC) transplantation. We used MSCs extracted from bone marrow (BMSCs) to transplant via the tail vein into a radiation-induced heart injury (RIHI) rat model. The rats were divided into six groups: a Sham group, an IRR (irradiation) group, and four IRR + BMSCs transplantation groups obtained at different time points...
December 26, 2016: Radiation and Environmental Biophysics
https://www.readbyqxmd.com/read/28012437/autophagy-deficient-keratinocytes-display-increased-dna-damage-senescence-and-aberrant-lipid-composition-after-oxidative-stress-in-vitro-and-in-vivo
#14
Xiuzu Song, Marie Sophie Narzt, Ionela Mariana Nagelreiter, Philipp Hohensinner, Lucia Terlecki-Zaniewicz, Erwin Tschachler, Johannes Grillari, Florian Gruber
Autophagy allows cells fundamental adaptations to metabolic needs and to stress. Using autophagic bulk degradation cells can clear crosslinked macromolecules and damaged organelles that arise under redox stress. Accumulation of such debris results in cellular dysfunction and is observed in aged tissue and senescent cells. Conversely, promising anti-aging strategies aim at inhibiting the mTOR pathway and thereby activating autophagy, to counteract aging associated damage. We have inactivated autophagy related 7 (Atg7), an essential autophagy gene, in murine keratinocytes (KC) and have found in an earlier study that this resulted in increased baseline oxidative stress and reduced capacity to degrade crosslinked proteins after oxidative ultraviolet stress...
April 2017: Redox Biology
https://www.readbyqxmd.com/read/28005992/do-exogenous-dna-double-strand-breaks-change-incomplete-synapsis-and-chiasma-localization-in-the-grasshopper-stethophyma-grossum
#15
Adela Calvente, Juan Luis Santos, Julio S Rufas
Meiotic recombination occurs as a programmed event that initiates by the formation of DNA double-strand breaks (DSBs) that give rise to the formation of crossovers that are observed as chiasmata. Chiasmata are essential for the accurate chromosome segregation and the generation of new combinations of parental alleles. Some treatments that provoke exogenous DSBs also lead to alterations in the recombination pattern of some species in which full homologous synapsis is achieved at pachytene. We have carried out a similar approach in males of the grasshopper Stethophyma grossum, whose homologues show incomplete synapsis and proximal chiasma localization...
2016: PloS One
https://www.readbyqxmd.com/read/27922110/%C3%AE-h2ax-53bp1-pkap-1-foci-and-their-linear-tracks-induced-by-in-vitro-exposure-to-radon-and-its-progeny-in-human-peripheral-blood-lymphocytes
#16
Defang Ding, Yaping Zhang, Jing Wang, Xufei Wang, Dunhuang Fan, Linfeng He, Xuxia Zhang, Yun Gao, Qiang Li, Honghong Chen
The biodosimetric information is critical for evaluating the human health hazards caused by radon and its progeny. Here, we demonstrated that the formation of phosphorylated histone variant H2AX (γ-H2AX), p53-binding protein 1 (53BP1) and phosphorylated KRAB-associated protein 1 (pKAP-1) foci and their linear tracks in human peripheral blood lymphocytes (HPBLs) in vitro exposed to radon and its progeny were dependent on the cumulative absorbed dose of radon exposure but was unrelated to the concentration of radon...
December 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27876069/mgdg-extracted-from-spinach-enhances-the-cytotoxicity-of-radiation-in-pancreatic-cancer-cells
#17
Hiroaki Akasaka, Yoshiyuki Mizushina, Kenji Yoshida, Yasuo Ejima, Naritoshi Mukumoto, Tianyuan Wang, Sachiko Inubushi, Masao Nakayama, Yuki Wakahara, Ryohei Sasaki
BACKGROUND: In our previous study, monogalactosyl diacylglycerol (MGDG) purified from spinach was found to have cytotoxic effects in human cancer cell lines. This study further assessed whether MGDG can enhance the cytotoxic effects of radiation in human pancreatic cancer cells in vitro and in vivo. METHODS: Glycoglycerolipids from spinach including MGDG were extracted from dried spinach. The cytotoxicity of MGDG were evaluated by the MTT assay using four human pancreatic cancer cell lines (MIAPaCa-2, AsPC-1, BxPC-3 and PANC-1) and normal human dermal fibroblasts (NHDFs)...
November 22, 2016: Radiation Oncology
https://www.readbyqxmd.com/read/27826196/the-medicinal-fungus-antrodia-cinnamomea-regulates-dna-repair-and-enhances-the-radiosensitivity-of-human-esophageal-cancer-cells
#18
Yu-Ming Liu, Yu-Kuo Liu, Ling-Wei Wang, Yu-Chuen Huang, Pin-I Huang, Tung-Hu Tsai, Yu-Jen Chen
This study investigated the adjunctive effects of Antrodia cinnamomea mycelial fermentation broth (AC-MFB), a Taiwanese medicinal fungus, in enhancing the radiosensitivity of esophageal cancer cells. Human CE81T/VGH squamous and BE3 adenocarcinoma esophageal cancer cells were used in this study. A colony formation assay showed that pretreatment with AC-MFB decreased the survival of irradiated esophageal cancer cells, with a maximum sensitizer enhancement ratio of 1.91% and 37% survival. A DNA histogram study showed that AC-MFB pretreatment enhanced cell cycle arrest at the G2/M phase, the most radiosensitive phase...
2016: OncoTargets and Therapy
https://www.readbyqxmd.com/read/27821478/mcl-1-depletion-impairs-dna-double-strand-break-repair-and-reinitiation-of-stalled-dna-replication-forks
#19
Abid R Mattoo, Raj K Pandita, Sharmistha Chakraborty, Vijaya Charaka, Kalpana Mujoo, Clayton R Hunt, Tej K Pandita
Myeloid cell leukemia 1 (MCL-1) is a prosurvival BCL-2 protein family member highly expressed in hematopoietic stem cells (HSCs) and regulated by growth factor signals that manifest antiapoptotic activity. Here we report that depletion of MCL-1 but not its isoform MCL-1S increases genomic instability and cell sensitivity to ionizing radiation (IR)-induced death. MCL-1 association with genomic DNA increased postirradiation, and the protein colocalized with 53BP1 foci. Postirradiation, MCL-1-depleted cells exhibited decreased γ-H2AX foci, decreased phosphorylation of ATR, and higher levels of residual 53BP1 and RIF1 foci, suggesting that DNA double-strand break (DSB) repair by homologous recombination (HR) was compromised...
February 1, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/27806616/development-of-a-transmission-alpha-particle-dosimetry-technique-using-a549-cells-and-a-ra-223-source-for-targeted-alpha-therapy
#20
R Al Darwish, A H Staudacher, Y Li, M P Brown, E Bezak
PURPOSE: In targeted radionuclide therapy, regional tumors are targeted with radionuclides delivering therapeutic radiation doses. Targeted alpha therapy (TAT) is of particular interest due to its ability to deliver alpha particles of high linear energy transfer within the confines of the tumor. However, there is a lack of data related to alpha particle distribution in TAT. These data are required to more accurately estimate the absorbed dose on a cellular level. As a result, there is a need for a dosimeter that can estimate, or better yet determine the absorbed dose deposited by alpha particles in cells...
November 2016: Medical Physics
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