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Radiation effects on dna

Kimberly M Arnold, Nicole J Flynn, Adam Raben, Lindsay Romak, Yan Yu, Adam P Dicker, Firas Mourtada, Jennifer Sims-Mourtada
In addition to inducing lethal DNA damage in tumor and stromal cells, radiation can alter the interactions of tumor cells with their microenvironment. Recent technological advances in planning and delivery of external beam radiotherapy have allowed delivery of larger doses per fraction (hypofractionation) while minimizing dose to normal tissues with higher precision. The effects of radiation on the tumor microenvironment vary with dose and fractionation schedule. In this review, we summarize the effects of conventional and hypofractionated radiation regimens on the immune system and tumor stroma...
2018: Cancer Growth and Metastasis
Cindy R Timme, Barbara H Rath, John W O'Neill, Kevin Camphausen, Philip J Tofilon
Radiotherapy is a primary treatment modality for glioblastomas (GBMs). Because DNA-PKcs is a critical factor in the repair of radiation-induced double strand breaks (DSBs), this study evaluated the potential of VX-984, a new DNA-PKcs inhibitor, to enhance the radiosensitivity of GBM cells. Treatment of the established GBM cell line U251 and the GBM stem-like cell (GSC) line NSC11 with VX-984 under in vitro conditions resulted in a concentration-dependent inhibition of radiation-induced DNA-PKcs phosphorylation...
March 16, 2018: Molecular Cancer Therapeutics
Yang Chen, Youyou Wang, Lujun Zhao, Ping Wang, Jifeng Sun, Rudi Bao, Chenghai Li, Ningbo Liu
Objective: To investigate the potential of HS-10182, a second-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), as a radiosensitizer in non-small cell lung cancer (NSCLC). Methods: Two cell lines of NSCLCs, A549 that possesses wild-type (WT) EGFRs and H1975 that possesses EGFR L858R/T790M double mutations, were treated with HS-10182 at various concentrations, and cell viabilities were determined using the MTS assay. The cells were tested by clonogenic survival assays to identify the radiosensitivity of both groups...
February 2018: Cancer Biology & Medicine
Samantha L Martin, Kendra J Royston, Trygve O Tollefsbol
Cancer is the second leading cause of mortalities in the United States, only exceeded by heart disease. Current cancer treatments include chemotherapy, surgery and/or radiation. Due to the often harsh effects of current cancer therapies, investigators are focusing their efforts on cancer prevention mediated by dietary phytochemicals. Since the discovery that cancer can be initiated by and progress through both genetic and epigenetic pathways, there has been a significant surge in studies on epigenetic effects mediated by nutritive compounds...
March 12, 2018: Molecular Nutrition & Food Research
Tatsuo Miyamoto, Silvia Natsuko Akutsu, Hiroshi Tauchi, Yoshiki Kudo, Satoshi Tashiro, Takashi Yamamoto, Shinya Matsuura
DNA double-strand breaks (DSBs) induced by ionizing radiation (IR) are the initial and critical step in major alteration of genetic information and cell death. To prevent deleterious effects, DNA repair systems recognize and re-join DNA DSBs in human cells. It has been suggested that there are individual differences in radiosensitivity within human populations, and that variations in DNA repair genes might contribute to this heterogeneity. Because confounding factors, including age, gender, smoking, and diverse genetic backgrounds within human populations, also influence the cellular radiosensitivity, to accurately measure the effect of candidate genetic variations on radiosensitivity, it is necessary to use human cultured cells with a uniform genetic background...
March 8, 2018: Journal of Radiation Research
Christoph Oing, Pierre Tennstedt, Ronald Simon, Jennifer Volquardsen, Kerstin Borgmann, Carsten Bokemeyer, Cordula Petersen, Ekkehard Dikomey, Kai Rothkamm, Wael Y Mansour
Here we report that BCL2 blocks DNA double strand break (DSB) repair via nonhomologous end-joining (NHEJ), through sequestration of KU80 protein outside the nucleus. We find that this effect is associated with a repair switch to the error-prone PARP1-dependent end-joining (PARP1-EJ). We present in-vitro proof-of-concept for therapeutic targeting of this switch using PARP inhibitor to specifically enhance the radiosensitivity of BCL2-overexpressing cells. Given its erroneous behavior, PARP1-EJ might allow for the accumulation of genetic alterations and tumor progression...
March 8, 2018: Cancer Letters
Sarita Pandey, Anurag Kirti, Arvind Kumar, Hema Rajaram
The ubiquitous SbcCD exonuclease complex has been shown to perform an important role in DNA repair across prokaryotes and eukaryotes. However, they have remained uncharacterized in the ancient and stress-tolerant cyanobacteria. In the cyanobacterium Anabaena sp. strain PCC7120, SbcC and SbcD homologs, defined on the basis of the presence of corresponding functional domains, are annotated as hypothetical proteins, namely Alr3988 and All4463 respectively. Unlike the presence of sbcC and sbcD genes in a bicistronic operon in most organisms, these genes were distantly placed on the chromosome in Anabaena, and found to be negatively regulated by LexA...
March 9, 2018: Functional & Integrative Genomics
Davide Moiani, Daryl A Ronato, Chris A Brosey, Andrew S Arvai, Aleem Syed, Jean-Yves Masson, Elena Petricci, John A Tainer
For inhibitor design, as in most research, the best system is question dependent. We suggest structurally defined allostery to design specific inhibitors that target regions beyond active sites. We choose systems allowing efficient quality structures with conformational changes as optimal for structure-based design to optimize inhibitors. We maintain that evolutionarily related targets logically provide molecular avatars, where this Sanskrit term for descent includes ideas of functional relationships and of being a physical embodiment of the target's essential features without requiring high sequence identity...
2018: Methods in Enzymology
Richard W Harbron, Elizabeth A Ainsbury, Simon D Bouffler, Rick J Tanner, Mark S Pearce, Jonathan S Eakins
Studies suggest iodinated contrast media (ICM) may increase organ dose and blood cell DNA damage for a given X-ray exposure. The impact of ICM on dose/damage to extravascular cells and cancer risks is unclear. METHODS: We used Monte Carlo modelling to investigate the microscopic distribution of absorbed dose outside the lumen of arteries, capillaries and interstitial fluids containing blood and various concentrations of iodine. Models were irradiated with four X-ray spectra representing clinical procedures...
February 2018: Physica Medica: PM
Lin Shi, Satoshi Tashiro
X-rays are widely applied in the medical field for the diagnosis and treatment of diseases. Among the uses of X-rays in diagnosis, computed tomography (CT) has been established as one of the most informative diagnostic radiology examinations. Moreover, recent advances in CT scan technology have made this examination much easier and more informative and increased its application, especially in Japan. However, the radiation dose of CT scans is higher than that of simple X-ray examinations. Therefore, the health risk of a CT scan has been discussed in various studies, but is still controversial...
March 6, 2018: Journal of Radiation Research
Seyed Jalal Hosseinimehr
: Background: Radiotherapy is an important protocol in the treatment of cancers, but radioresistance of cancerous cells is a challenge in cancer treatment. OBJECTIVE: The aim of this study was to evaluate the radiosensitizing effect of cerium oxide nanoparticles (CNPs) on human promyelocytic leukemia cells (HL-60). METHOD: HL-60 cells were treated with CNPs at different concentrations (10-100 µg/ml) and exposed to ionizing radiation (IR). The genotoxicity effects of CNPs or/and IR were assessed by micronuclei assay in HL-60 cells...
March 6, 2018: Pharmaceutical Nanotechnology
Jiani Xie, Ning Wang, Xinghua Dong, Chengyan Wang, Zhen Du, Linqiang Mei, Yuan Yong, Changshui Huang, Yuliang Li, Zhanjun Gu, Yuliang Zhao
Numerous carbon networks materials comprised of benzene moieties, such as graphene and fullerene, have held great fascination for radioprotection because of their acknowledged good biocompatibility and strong free radical scavenging activity derived from their delocalized π-conjugated structure. Recently, graphdiyne, a new emerging carbon network material consisting of a unique chemical structure of benzene and acetylenic moieties, has gradually attracted attention in many research fields. Encouraged by its unique structure with strong conjugated π-system and highly reactive diacetylenic linkages, graphdiyne might have free radical activity and can thus be used as a radioprotector, which has not been investigated so far...
March 6, 2018: ACS Applied Materials & Interfaces
Mario Pietro Carante, Chiara Aimè, John James Tello Cajiao, Francesca Ballarini
An upgraded version of the BIANCA II biophysical model was applied to a low- and a high- α/β ratio cell line (V79 and AG01522, respectively) exposed to protons, C-ions and He-ions over a wide LET interval (0.6-30.5 keV/μm for protons, 22.5-502 keV/μm for C-ions, 16.2-132 keV/μm for He-ions). The model assumes that i) ionizing radiation induces DNA "Cluster Lesions" (CLs), where by definition each CL produces two independent chromosome fragments; ii) fragment un-rejoining, or distance-dependent mis-rejoining, produces chromosome aberrations; iii) some aberrations lead to cell death...
March 6, 2018: Physics in Medicine and Biology
Luděk Vyšín, Tomáš Burian, Egor Ukraintsev, Marie Davídková, Michael E Grisham, Scott Heinbuch, Jorge J Rocca, Libor Juha
In this study, we examined dose-rate effects on strand break formation in plasmid DNA induced by pulsed extreme ultraviolet (XUV) radiation. Dose delivered to the target molecule was controlled by attenuating the incident photon flux using aluminum filters as well as by changing the DNA/buffer-salt ratio in the irradiated sample. Irradiated samples were examined using agarose gel electrophoresis. Yields of single- and double-strand breaks (SSBs and DSBs) were determined as a function of the incident photon fluence...
March 5, 2018: Radiation Research
Masoud Najafi, Mohsen Cheki, Saeed Rezapoor, Ghazale Geraily, Elahe Motevaseli, Carla Carnovale, Emilio Clementi, Alireza Shirazi
The diabetes drug metformin can mitigate the genotoxic effects of cytotoxic agents and has been proposed to prevent or even cure certain cancers. Metformin reduces DNA damage by mechanisms that are only incompletely understood. Metformin scavenges free radicals, including reactive oxygen species and nitric oxide, which are produced by genotoxicants such as ionizing or non-ionizing radiation, heavy metals, and chemotherapeutic agents. The drug may also increase the activities of antioxidant enzymes and inhibit NADPH oxidase, cyclooxygenase-2, and inducible nitric oxide synthase, thereby limiting macrophage recruitment and inflammatory responses...
March 2018: Mutation Research
Michael Rückert, Lisa Deloch, Rainer Fietkau, Benjamin Frey, Markus Hecht, Udo S Gaipl
BACKGROUND: Radiotherapy (RT) has been known for decades as a local treatment modality for malign and benign disease. In order to efficiently exploit the therapeutic potential of RT, an understanding of the immune modulatory properties of ionizing radiation is mandatory. These should be used for improvement of radioimmunotherapies for cancer in particular. METHODS: We here summarize the latest research and review articles about immune modulatory properties of RT, with focus on radiation dose and on combination of RT with selected immunotherapies...
March 2, 2018: Strahlentherapie und Onkologie: Organ der Deutschen Röntgengesellschaft ... [et Al]
Samir A Salama, Hany H Arab, Hany A Omar, Hesham S Gad, Gamil M Abd-Allah, Ibrahim A Maghrabi, Majed M Al Robaian
UVA comprises more than 90% of the solar UV radiation reaching the Earth. Artificial lightening lamps have also been reported to emit significant amounts of UVA. Exposure to UVA has been associated with dermatological disorders including skin cancer. At the molecular level, UVA damages different cellular biomolecules and triggers inflammatory responses. The current study was devoted to investigate the potential protective effect of L-carnitine against UVA-induced skin tissue injury using rats as a mammalian model...
February 27, 2018: Chemico-biological Interactions
John James Tello Cajiao, Mario Pietro Carante, Mario Antonio Bernal Rodriguez, Francesca Ballarini
It is widely accepted that, in chromosome-aberration induction, the (mis-)rejoining probability of two chromosome fragments depends on their initial distance, r. However, several aspects of these "proximity effects" need to be clarified, also considering that they can vary with radiation quality, cell type and dose. A previous work performed by the BIANCA (BIophysical ANalysis of Cell death and chromosome Aberrations) biophysical model has suggested that, in human lymphocytes and fibroblasts exposed to low-LET radiation, an exponential function of the form exp(-r/r0 ), which is consistent with free-end (confined) diffusion, describes proximity effects better than a Gaussian function...
February 22, 2018: DNA Repair
Sherise D Ferguson, Shouhao Zhou, Joanne Xiu, Yuuri Hashimoto, Nader Sanai, Lyndon Kim, Santosh Kesari, John de Groot, David Spetzler, Amy B Heimberger
Background: After surgery and radiation, treatment options for ependymoma are few making recurrence a challenging issue. Specifically, the efficacy of chemotherapy at recurrence is limited. We performed molecular profiling on a cohort of ependymoma cases in order to uncover therapeutic targets and to elucidate the molecular mechanisms contributing to treatment resistance. Results: This ependymoma cohort showed minimal alterations in gene amplifications and mutations but had high expression rates of DNA synthesis and repair enzymes such as RRM1 (47%), ERCC1 (48%), TOPO1 (62%) and class III β-tublin (TUBB3) (57%), which are also all associated with chemoresistance...
January 30, 2018: Oncotarget
Marie Trijau, Jana Asselman, Olivier Armant, Christelle Adam-Guillermin, Karel Ac De Schamphelaere, Frédéric Alonzo
Our aim was to investigate epigenetic changes in Daphnia magna after a 25-day chronic external gamma irradiation (generation F0 exposed to 6.5 µGy h-1 or 41.3 mGy h-1) and their potential inheritance by subsequent recovering generations, namely F2 (exposed as germline cells in F1 embryos) and F3 (the first truly unexposed generation). Effects on survival, growth and reproduction were observed and DNA was extracted for whole genome bisulfite sequencing in all generations. Results showed effects on reproduction in F0 but no effect in the subsequent generations F1, F2 and F3...
February 27, 2018: Environmental Science & Technology
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