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Radiation Research

Michael M Im, Sheryl A Flanagan, Jeffrey J Ackroyd, Brendan Knapp, Aaron Kramer, Donna S Shewach
Gemcitabine (dFdCyd) shows broad antitumor activity in solid tumors in chemotherapeutic regimens or when combined with ionizing radiation (radiosensitization). While it is known that mismatches in DNA are necessary for dFdCyd radiosensitization, the critical event resulting in radiosensitization has not been identified. Here we hypothesized that late DNA damage (≥24 h after drug washout/irradiation) is a causal event in radiosensitization by dFdCyd, and that homologous recombination repair (HRR) is required for this late DNA damage...
October 14, 2016: Radiation Research
David B Hanbury, Ann M Peiffer, Greg Dugan, Rachel N Andrews, J Mark Cline
In this study, the effects of a potentially lethal radiation exposure on the brain for long-term cognitive sequelae were investigated, using Rhesus macaques ( Macaca mulatta ) adopted from other facilities after analysis of acute radiation response via the Centers for Medical Countermeasures against Radiation (CMCR) network. Fifty-nine animals were given the opportunity to participate in cognitive cage-side testing. The animals that received single-dose gamma irradiation were significantly less likely to engage in cognitive testing than the controls, suggesting that irradiated animals may have differences in cognitive ability...
October 14, 2016: Radiation Research
Katharina Gläser, Martina Rohland, Thomas Kleine-Ostmann, Thorsten Schrader, Helga Stopper, Henning Hintzsche
Exposure to electromagnetic fields in the radiofrequency range is ubiquitous, mainly due to the worldwide use of mobile communication devices. With improving technologies and affordability, the number of cell phone subscriptions continues to increase. Therefore, the potential effect on biological systems at low-intensity radiation levels is of great interest. While a number of studies have been performed to investigate this issue, there has been no consensus reached based on the results. The goal of this study was to elucidate the extent to which cells of the hematopoietic system, particularly human hematopoietic stem cells (HSC), were affected by mobile phone radiation...
October 6, 2016: Radiation Research
Margaret L Barlow, Ryan J Cummings, Alice P Pentland, Tanzy M T Love, Constantine G Haidaris, Julie L Ryan, Edith M Lord, Scott A Gerber
Exposure to radiation, particularly a large or total-body dose, weakens the immune system through loss of bone marrow precursor cells, as well as diminished populations of circulating and tissue-resident immune cells. One such population is the skin-resident immune cells. Changes in the skin environment can be of particular importance as the skin is also host to a number of commensal organisms, including Candida albicans , a species of fungus that causes opportunistic infections in immunocompromised patients...
October 6, 2016: Radiation Research
Mary Sproull, Kevin Camphausen
With the possibility of large-scale terrorist attacks around the world, the need for modeling and development of new medical countermeasures for potential future chemical, biological, radiological and nuclear (CBRN) has been well established. Project Bioshield, initiated in 2004, provided a framework to develop and expedite research in the field of CBRN exposures. To respond to large-scale population exposures from a nuclear event or radiation dispersal device (RDD), new methods for determining received dose using biological modeling became necessary...
October 6, 2016: Radiation Research
I Deltour, Y Tsareva, S J Schonfeld, V V Vostrotin, P Okatenko, M Sokolnikov, J Schüz
Long-term effects of in utero exposure to ionizing radiation remain poorly quantified in humans. In this study, the risk of hematologic malignancies was investigated in offspring of female workers of the Mayak Production Association, a large Russian nuclear facility. Excess relative risks (ERR) for exposure to gamma radiation and plutonium were estimated in a cohort of 8,466 offspring who were born between January 1, 1948 and December 31, 1988 and followed until 2009. An unstable linear ERR of 1.12 (95% CI 0...
September 30, 2016: Radiation Research
Chizuru Tsuruoka, Benjamin Blyth, Takamitsu Morioka, Mutsumi Kaminishi, Mayumi Shinagawa, Yoshiya Shimada, Shizuko Kakinuma
Recently reported studies have led to a heightened awareness of the risks of cancer induced by diagnostic radiological imaging, and in particular, the risk of brain cancer after childhood CT scans. One feature of Ptch1(+/-) mice is their sensitivity to radiation-induced medulloblastomas (an embryonic cerebellar tumor) during a narrow window of time centered on the days around birth. Little is known about the dynamics of how dose protraction interacts with such narrow windows of sensitivity in individual tissues...
September 30, 2016: Radiation Research
Nong Yang, Xican Gao, Xiaofei Qu, Ruiguang Zhang, Fan Tong, Qian Cai, Jihua Dong, Yu Hu, Gang Wu, Xiaorong Dong
Radiation-induced brain injury (RIBI) is the most common adverse effect that occurs after cranial radiation therapy (CRT). We have previously reported that CRT-induced release of pro-inflammatory cytokines in brain tissues and inhibition of neurogenesis in the hippocampus might be caused by microglial activation and may play an important role in RIBI. In this study we examined the role of p53-induced protein with a death domain (PIDD) in radiation-induced activation of BV-2 cells. BV-2 cells were transfected with antisense oligonucleotide control mRNA or antisense oligonucleotide-targeted PIDD mRNA and were sham or 16 Gy irradiated...
September 19, 2016: Radiation Research
Xiaoyan Fan, Yan Li, Yulong Zhang, Meixiang Sang, Jianhui Cai, Qiaoxia Li, Toshinori Ozaki, Tetsuya Ono, Dongwei He
To elucidate the role of the mismatch repair gene Mlh1 in genome instability during the fetal stage, spontaneous mutations were studied in Mlh1-deficient lacZ-transgenic mouse fetuses. Mutation levels were high at 9.5 days post coitum (dpc) and gradually increased during the embryonic stage, after which they remained unchanged. In addition, mutations that were found in brain, liver, spleen, small intestine and thymus showed similar levels and no statistically significant difference was found. The molecular nature of mutations at 12...
September 19, 2016: Radiation Research
Christopher Rabender, Eleonora Mezzaroma, Adolfo G Mauro, Ramesh Mullangi, Antonio Abbate, Mitchell Anscher, Barry Hart, Ross Mikkelsen
There is an ongoing and significant need for radiation countermeasures to reduce morbidities and mortalities associated with exposure of the heart and lungs from a radiological or nuclear incidents. Radiation-induced late effects occur months to years after exposure, stemming from significant tissue damage and remodeling, resulting in fibrosis and loss of function. TGF-β is reported to play a role in both pulmonary and cardiac fibrosis. We investigated the ability of a small molecule TGF-β receptor 1 inhibitor, IPW-5371, to mitigate the effects of thoracic irradiation in C57L/J mice, a murine model that most closely resembles that observed in humans in the induction of fibrosis and dose response...
September 19, 2016: Radiation Research
Samuel N Rodman, Jacquelyn M Spence, Tyler J Ronnfeldt, Yueming Zhu, Shane R Solst, Rebecca A O'Neill, Bryan G Allen, Xiangming Guan, Douglas R Spitz, Melissa A Fath
The goal of this study was to determine if depletion of glutathione (GSH) and inhibition of thioredoxin (Trx) reductase (TrxR) activity could enhance radiation responses in human breast cancer stem cells by a mechanism involving thiol-dependent oxidative stress. The following were used to inhibit GSH and Trx metabolism: buthionine sulfoximine (BSO), a GSH synthesis inhibitor; sulfasalazine (SSZ), an inhibitor of xc(-) cysteine/glutamate antiporter; auranofin (Au), a thioredoxin reductase inhibitor; or 2-AAPA, a GSH-reductase inhibitor...
September 19, 2016: Radiation Research
K Hamasaki, R D Landes, A Noda, N Nakamura, Y Kodama
While it is generally believed that fetuses are at high risk of developing cancers, including leukemia, after low doses of radiation, it has been reported that atomic bomb survivors exposed in utero did not show a dose response for translocations in blood T lymphocytes when they were examined at approximately 40 years of age. Subsequent mouse studies confirmed that animals irradiated during the fetal stage did not show evidence of radiation effects in lymphocytes and bone marrow cells when they were examined after reaching adulthood...
September 14, 2016: Radiation Research
Kengo Yoshida, Munechika Misumi, Yoshiko Kubo, Mika Yamaoka, Seishi Kyoizumi, Waka Ohishi, Tomonori Hayashi, Yoichiro Kusunoki
In a series of studies of atomic bomb survivors, radiation-dose-dependent alterations in peripheral T-cell populations have been reported. For example, reduced size in naïve T-cell pools and impaired proliferation ability of T cells were observed. Because these alterations are also generally observed with human aging, we hypothesized that radiation exposure may accelerate the aging process of the T-cell immune system. To further test this hypothesis, we conducted cross-sectional analyses of telomere length, a hallmark of cellular aging, of naïve and memory CD4 T cells and total CD8 T cells in the peripheral blood of 620 atomic bomb survivors as it relates to age and radiation dose, using fluorescence in situ hybridization with flow cytometry...
September 14, 2016: Radiation Research
J S Willey, A T Kwok, J E Moore, V Payne, C A Lindburg, S A Balk, J Olson, P J Black, M C Walb, R R Yammani, M T Munley
There is little known about the effect of both reduced weight bearing and exposure to radiation during spaceflight on the mechanically-sensitive cartilage lining the knee joint. In this study, we characterized cartilage damage in rat knees after periods of reduced weight bearing with/without exposure to solar-flare-relevant radiation, then cartilage recovery after return to weight bearing. Male Sprague Dawley rats (n = 120) were either hindlimb unloaded (HLU) via tail suspension or remained weight bearing in cages (GROUND)...
September 7, 2016: Radiation Research
Ludwik Dobrzyński, Krzysztof W Fornalski, Yehoshua Socol, Joanna M Reszczyńska
We report here on various biophysical aspects of irradiated cells, beginning with a phenomenological description of radiation-induced cancer cells. This description includes detrimental factors such as chromosomal aberrations, as well as beneficial factors, such as adaptive response. Also discussed here is the dose- and time-dependent evolution of cancer cells using a purely mathematical approach. The general dose-response shape, which is sigmoidal, is shown to be modified by such mechanisms as adaptive response or bystander effect...
September 2, 2016: Radiation Research
David A Gewirtz, Moureq Alotaibi, Vasily A Yakovlev, Lawrence F Povirk
Inhibitors of poly(ADP-ribose) polymerase (PARP) are clinically used as single-agent therapy for tumors with BRCA1 or BRCA2 mutations. One approach to expanding the use of PARP inhibitors to a wider range of tumors is to combine them with cytotoxic chemotherapy or radiotherapy. Preclinical studies in experimental animals and tumor cells in culture indicate that PARP inhibition modestly sensitizes most tumor cells to ionizing radiation. Studies of cell behavior after these combined treatments show that radiosensitization is manifested predominantly in an increase in prolonged growth arrest and senescence, with little or no contribution from apoptosis...
September 2, 2016: Radiation Research
Jiang-Zhou Yu, Matt Lindeblad, Alex Lyubimov, Flavia Neri, Brett Smith, Erzsebet Szilagyi, Lisa Halliday, Tom MacVittie, Joy Nanda, Amelia Bartholomew
No abstract text is available yet for this article.
September 2016: Radiation Research
David A Edmondson, Erin E Karski, Ayano Kohlgruber, Harsha Koneru, Katherine K Matthay, Shelly Allen, Christine L Hartmann, Leif E Peterson, Steven G DuBois, Matthew A Coleman
Calculating internal dose from therapeutic radionuclides currently relies on estimates made from multiple radiation exposure measurements, converted to absorbed dose in specific organs using the Medical Internal Radiation Dose (MIRD) schema. As an alternative biodosimetric approach, we utilized gene expression analysis of whole blood from patients receiving targeted radiotherapy. Collected blood from patients with relapsed or refractory neuroblastoma who received (131)I-labeled metaiodobenzylguanidine ((131)I-mIBG) at the University of California San Francisco (UCSF) was used to compare calculated internal dose with the modulation of chosen gene expression...
September 2016: Radiation Research
Kensuke Otsuka, Keiji Suzuki
The protection of intestinal epithelial cells from the lethal effects induced by high-dose radiation is an important issue in radiotherapy and in the treatment of acute radiation syndrome. However, the effects of middle- and low-dose radiation on intestinal epithelial cells remain unclear. Because the accumulation of DNA damage in intestinal stem cells may be crucial for the development of cancer-initiating cells, it is important to understand the kinetics of DNA repair and tissue response (which are involved in the elimination of damaged cells and tissue injury repair) to middle- to low-dose irradiation...
September 2016: Radiation Research
Joseph T Rakowski, Mark A Tucker, Michael G Snyder, Simon P Makar, Mark Yudele, Jay Burmeister, Michael C Joiner
Characteristic X rays of energies less than approximately 20 keV are of interest in radiobiology and radiation oncology. There is evidence that these low-energy photons produce higher relative biological effectiveness (RBE) and lower oxygen enhancement ratio (OER) relative to higher energies. Lower energy X rays also offer the advantage of healthy tissue sparing beyond the target treatment depth. Electronic brachytherapy systems that can deliver characteristic and bremsstrahlung X rays of varying energy are in clinical use as well as under development...
September 2016: Radiation Research
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