Radiation Bystander Effects: Mechanisms

Summary

Principal Investigator: Tom K Hei
Abstract: Radiation induced non-targeted/bystander effects have been demonstrated with a variety of biological endpoints using mammalian cell cultures, 3D human tissues, and more recently, in C. elegans and in mice. However, neither the mechanism nor the relevance of the bystander response to human health is clear. This program project brings together and links 3 highly integrated projects aimed at shedding new light on the mechanism and health relevance of the non-targeted/bystander phenomenon using both in vitro and in vivo approaches. The overall hypothesis of this program project is that the radiation induced non-targeted (bystander) response can be initiated both in vitro and in vivo by oxidative stress and propagated by multifactorial signaling events involving cyclooxygenase-2 (COX-2) and junctional communication, and is modulated by the status of the Rad9 protein. The three projects are highly interactive in goals and research approaches and are further linked together by a technical core, which will provide specialized irradiation facilities, data analyses and state-of-the-art gene expression profile related technologies. Project 1 will address the role of Rad9, a DNA damage response protein, in the radiation induced bystander effect in mouse embryo fibroblasts (MEF) and mice. The underlying hypothesis to be tested is that Rad9 controls the bystander process via regulation of COX-2, p21Waf1 and other downstream targets. Project 2 will build on the preliminary findings that radiation induces non-targeted, out of field mutagenesis in lung tissues of gpt delta transgenic mice to test the hypothesis that COX-2 mediates radiation-induced bystander mutagenesis in vivo and that the bystander cells are genomically unstable in genetically susceptible populations. Project 3 will address the central hypothesis that the in vivo cellular microenvironment modulates gap junction gating that determines the nature of signaling events propagated between directly-irradiated and bystander cells. The projects are conceptually linked and technically interactive such that they complement cross-talk and strengthen each other. The observation that the progeny of non-targeted cells show an increase in genomic instability as evidenced by an increase in delayed mutations and chromosomal aberrations many generations post-irradiation indicate the need for a comprehensive assessment of the bystander issue, particularly among genetically susceptible population, to understand mechanism(s) and impact on human health.
Funding Period: 1997-02-01 - 2015-06-30
more information: NIH RePORT

Top Publications

  1. pmc Mechanism of radiation carcinogenesis: role of the TGFBI gene and the inflammatory signaling cascade
    Tom K Hei
    Department of Radiation Oncology, Columbia University Medical Center, New York, NY 10032, USA
    Adv Exp Med Biol 720:163-70. 2011
  2. pmc Contributions of Rad9 to tumorigenesis
    Constantinos G Broustas
    Center for Radiological Research, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA
    J Cell Biochem 113:742-51. 2012
  3. pmc Intrachromosomal changes and genomic instability in site-specific microbeam-irradiated and bystander human-hamster hybrid cells
    Burong Hu
    Center for Radiological Research, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA
    Radiat Res 177:25-34. 2012
  4. pmc Ionizing radiation-induced metabolic oxidative stress and prolonged cell injury
    Edouard I Azzam
    Department of Radiology, UMDNJ New Jersey Medical School Cancer Center, Newark, 07103, United States
    Cancer Lett 327:48-60. 2012
  5. pmc Role of the translationally controlled tumor protein in DNA damage sensing and repair
    Jie Zhang
    Departments of Radiology, Pharmacology and Physiology, and Biochemistry and Molecular Biology, New Jersey Medical School Cancer Center, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103
    Proc Natl Acad Sci U S A 109:E926-33. 2012
  6. pmc Increased frequency of spontaneous neoplastic transformation in progeny of bystander cells from cultures exposed to densely ionizing radiation
    Manuela Buonanno
    Department of Radiology, University of Medicine and Dentistry of New Jersey, New Jersey Medical School Cancer Center, Newark, New Jersey, United States of America
    PLoS ONE 6:e21540. 2011
  7. pmc Detection of chromosomal instability in bystander cells after Si490-ion irradiation
    Brian Ponnaiya
    Center for Radiological Research, Mailman School of Public Health, Columbia University, New York, NY 10322, USA
    Radiat Res 176:280-90. 2011
  8. pmc Time-series clustering of gene expression in irradiated and bystander fibroblasts: an application of FBPA clustering
    Shanaz A Ghandhi
    Center for Radiological Research, Columbia University, New York, NY 10032, USA
    BMC Genomics 12:2. 2011
  9. pmc The role of RAD9 in tumorigenesis
    Howard B Lieberman
    Center for Radiological Research, Columbia University College of Physicians and Surgeons, 630 W 168th St, New York, NY 10032, USA
    J Mol Cell Biol 3:39-43. 2011
  10. pmc Long-term consequences of radiation-induced bystander effects depend on radiation quality and dose and correlate with oxidative stress
    Manuela Buonanno
    Department of Radiology, UMDNJ New Jersey Medical School Cancer Center, Newark, New Jersey 07103, USA
    Radiat Res 175:405-15. 2011

Detail Information

Publications81

  1. pmc Mechanism of radiation carcinogenesis: role of the TGFBI gene and the inflammatory signaling cascade
    Tom K Hei
    Department of Radiation Oncology, Columbia University Medical Center, New York, NY 10032, USA
    Adv Exp Med Biol 720:163-70. 2011
    ..The involvement of NFκB-dependent cytokines and the resultant inflammatory response works in concert with in modulating radiation-induced bronchial carcinogenesis...
  2. pmc Contributions of Rad9 to tumorigenesis
    Constantinos G Broustas
    Center for Radiological Research, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA
    J Cell Biochem 113:742-51. 2012
    ....
  3. pmc Intrachromosomal changes and genomic instability in site-specific microbeam-irradiated and bystander human-hamster hybrid cells
    Burong Hu
    Center for Radiological Research, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA
    Radiat Res 177:25-34. 2012
    ..These results suggest that genomic instability that is manifested after ionizing radiation exposure is not dependent on direct damage to the cell nucleus...
  4. pmc Ionizing radiation-induced metabolic oxidative stress and prolonged cell injury
    Edouard I Azzam
    Department of Radiology, UMDNJ New Jersey Medical School Cancer Center, Newark, 07103, United States
    Cancer Lett 327:48-60. 2012
    ..These include short and long-term in vitro and in vivo effects on mitochondrial DNA, mitochondrial protein import and metabolic and antioxidant enzymes...
  5. pmc Role of the translationally controlled tumor protein in DNA damage sensing and repair
    Jie Zhang
    Departments of Radiology, Pharmacology and Physiology, and Biochemistry and Molecular Biology, New Jersey Medical School Cancer Center, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103
    Proc Natl Acad Sci U S A 109:E926-33. 2012
    ..It also attenuated the radiation-induced G(1) delay but prolonged the G(2) delay. TCTP therefore may play a critical role in maintaining genomic integrity in response to DNA-damaging agents...
  6. pmc Increased frequency of spontaneous neoplastic transformation in progeny of bystander cells from cultures exposed to densely ionizing radiation
    Manuela Buonanno
    Department of Radiology, University of Medicine and Dentistry of New Jersey, New Jersey Medical School Cancer Center, Newark, New Jersey, United States of America
    PLoS ONE 6:e21540. 2011
    ....
  7. pmc Detection of chromosomal instability in bystander cells after Si490-ion irradiation
    Brian Ponnaiya
    Center for Radiological Research, Mailman School of Public Health, Columbia University, New York, NY 10322, USA
    Radiat Res 176:280-90. 2011
    ..The results presented here highlight the importance of nontargeted effects of radiation on chromosomal instability in human epithelial cells and their potential relevance to human health...
  8. pmc Time-series clustering of gene expression in irradiated and bystander fibroblasts: an application of FBPA clustering
    Shanaz A Ghandhi
    Center for Radiological Research, Columbia University, New York, NY 10032, USA
    BMC Genomics 12:2. 2011
    ..We compared our results with those of an alternate clustering method, Short Time series Expression Miner (STEM)...
  9. pmc The role of RAD9 in tumorigenesis
    Howard B Lieberman
    Center for Radiological Research, Columbia University College of Physicians and Surgeons, 630 W 168th St, New York, NY 10032, USA
    J Mol Cell Biol 3:39-43. 2011
    ..It is not clear which of the many functions of RAD9 is critical for carcinogenesis, but several alternatives are considered herein and implications for the development of novel cancer therapies based on these findings are examined...
  10. pmc Long-term consequences of radiation-induced bystander effects depend on radiation quality and dose and correlate with oxidative stress
    Manuela Buonanno
    Department of Radiology, UMDNJ New Jersey Medical School Cancer Center, Newark, New Jersey 07103, USA
    Radiat Res 175:405-15. 2011
    ..They are relevant to estimates of health risks from exposures to space radiation and the emergence of second malignancies after radiotherapy...
  11. pmc The role of gap junction communication and oxidative stress in the propagation of toxic effects among high-dose α-particle-irradiated human cells
    Narongchai Autsavapromporn
    Department of Radiology, UMDNJ New Jersey Medical School Cancer Center, Newark, New Jersey 07103, USA
    Radiat Res 175:347-57. 2011
    ....
  12. pmc Radiation response and regulation of apoptosis induced by a combination of TRAIL and CHX in cells lacking mitochondrial DNA: a role for NF-κB-STAT3-directed gene expression
    Vladimir N Ivanov
    Center for Radiological Research, Department of Radiation Oncology, College of Physicians and Surgeons, Columbia University, New York, USA
    Exp Cell Res 317:1548-66. 2011
    ....
  13. pmc TGFBI expression reduces in vitro and in vivo metastatic potential of lung and breast tumor cells
    Gengyun Wen
    Center for Radiological Research, College of Physicians and Surgeons, Columbia University, New York, NY, USA
    Cancer Lett 308:23-32. 2011
    ..Taken together, these data suggest that TGFBI moderates the metastatic potential of cancer cells...
  14. pmc Transforming growth factor-β-induced protein (TGFBI) suppresses mesothelioma progression through the Akt/mTOR pathway
    Gengyun Wen
    Center for Radiological Research, College of Physicians and Surgeons, Columbia University Medical Center, New York, NY, USA
    Int J Oncol 39:1001-9. 2011
    ..These findings suggest that TGFBI may repress mesothelioma tumorigenesis and progression via the PI3K/Akt signaling pathway...
  15. pmc Dynamic equilibrium between cancer stem cells and non-stem cancer cells in human SW620 and MCF-7 cancer cell populations
    G Yang
    State Key Laboratory of Nuclear Physics and Technology, School of Physics, Peking University, Beijing, People s Republic of China
    Br J Cancer 106:1512-9. 2012
    ..Cancer stem cells (CSCs) paradigm suggests that CSCs might have important clinical implications in cancer therapy. Previously, we reported that accumulation efficiency of CSCs is different post low- and high-LET irradiation in 48 h...
  16. pmc Mitochondrial alteration in malignantly transformed human small airway epithelial cells induced by α-particles
    Suping Zhang
    Center for Radiological Research, College of Physicians and Surgeons, Columbia University Medical Center, New York 10032, USA
    Int J Cancer 132:19-28. 2013
    ....
  17. pmc Human umbilical-cord-blood mononucleated cells enhance the survival of lethally irradiated mice: dosage and the window of time
    Olga A Kovalenko
    Department of Pathology and Laboratory Medicine, University of Medicine and Dentistry of New Jersey New Jersey Medical School, 185 South Orange Avenue, Newark, NJ 07103, USA
    J Radiat Res 54:1010-4. 2013
    ..01). Compared with earlier studies, the increased dose of HUCB mononucleated cells, coupled with early use of an antibiotic, extended the window of time for effective treatment of severe radiation injury from 4 to 24-52 h after exposure. ..
  18. pmc Participation of gap junction communication in potentially lethal damage repair and DNA damage in human fibroblasts exposed to low- or high-LET radiation
    Narongchai Autsavapromporn
    Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba 263 8555, Japan
    Mutat Res 756:78-85. 2013
    ..Together, our results show that PLDR and induction of DNA damage clearly depend on gap-junction communication and radiation quality. ..
  19. pmc Single-cell responses to ionizing radiation
    Brian Ponnaiya
    Center for Radiological Research, Columbia University, 630 West 168th Street, VC11 240, New York, NY, 10032, USA
    Radiat Environ Biophys 52:523-30. 2013
    ..This in turn points to the value of single-cell analyses. ..
  20. pmc Cytoplasmic irradiation results in mitochondrial dysfunction and DRP1-dependent mitochondrial fission
    Bo Zhang
    Authors Affiliations Center for Radiological Research, College of Physicians and Surgeons Department of Radiation Oncology, Columbia University, New York, New York and Biochemistry Section, National Institute for Neurological Disorders and Stroke, NIH, Bethesda, Maryland
    Cancer Res 73:6700-10. 2013
    ..Taken together, our results provide a mechanistic explanation for the extranuclear, nontargeted effects of ionizing radiation...
  21. pmc Health risks of space exploration: targeted and nontargeted oxidative injury by high-charge and high-energy particles
    Min Li
    1 Department of Radiology, Cancer Center, Rutgers University New Jersey Medical School, Newark, New Jersey
    Antioxid Redox Signal 20:1501-23. 2014
    ....
  22. pmc A role for TRAIL/TRAIL-R2 in radiation-induced apoptosis and radiation-induced bystander response of human neural stem cells
    Vladimir N Ivanov
    Center for Radiological Research, Department of Radiation Oncology, College of Physicians and Surgeons, Columbia University, 630 West 168th Street, New York, NY, 10032, USA
    Apoptosis 19:399-413. 2014
    ..Intercellular communication between cancer cells and NSC could potentially be involved in amplification of cancer pathology in the brain. ..
  23. pmc DNA damage response genes and the development of cancer metastasis
    Constantinos G Broustas
    a Center for Radiological Research, Columbia University College of Physicians and Surgeons, New York, New York 10032
    Radiat Res 181:111-30. 2014
    ..Importantly, despite some compelling in vitro evidence, investigations are still needed to demonstrate the role of cell cycle checkpoint and DNA repair genes in regulating metastatic phenotypes in vivo. ..
  24. pmc Nontargeted stressful effects in normal human fibroblast cultures exposed to low fluences of high charge, high energy (HZE) particles: kinetics of biologic responses and significance of secondary radiations
    Geraldine Gonon
    Department of Radiology, UMDNJ New Jersey Medical School Cancer Center, Newark, New Jersey, USA
    Radiat Res 179:444-57. 2013
    ..Thus, the latter are unlikely to significantly contribute to stressful effects in cells not targeted by primary HZE particles...
  25. pmc Radiation-induced non-targeted response in vivo: role of the TGFβ-TGFBR1-COX-2 signalling pathway
    Y Chai
    Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY, USA
    Br J Cancer 108:1106-12. 2013
    ..However, the signalling pathways involved in such effects remain unclear...
  26. pmc The role of TGFBI in mesothelioma and breast cancer: association with tumor suppression
    Bingyan Li
    School of Radiation Medicine and Public Health, Soochow University, Suzhou, China
    BMC Cancer 12:239. 2012
    ..In this study, ectopic expression of TGFBI was used to ascertain its role as a tumor suppressor and to determine the underlying mechanism of mesothelioma and breast cancer...
  27. pmc Radon-induced reduced apoptosis in human bronchial epithelial cells with knockdown of mitochondria DNA
    Bing Yan Li
    Department of Toxicology, School of Public Health, Soochow University, Suzhou, China
    J Toxicol Environ Health A 75:1111-9. 2012
    ..Our study indicates that the use of the ρ- knockdown mtDNA HBE cells may serve as a reliable model to study the role played by mitochondria in carcinogenic diseases...
  28. pmc Rad9 protein contributes to prostate tumor progression by promoting cell migration and anoikis resistance
    Constantinos G Broustas
    Center for Radiological Research, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA
    J Biol Chem 287:41324-33. 2012
    ..We thus demonstrate for the first time that Rad9 contributes to prostate tumorigenesis by increasing not only tumor proliferation and survival but also tumor migration and invasion, anoikis resistance, and anchorage-independent growth...
  29. pmc Human cell responses to ionizing radiation are differentially affected by the expressed connexins
    Narongchai Autsavapromporn
    Department of Radiology, New Jersey Medical School Cancer Center, Newark NJ 07103 USA
    J Radiat Res 54:251-9. 2013
    ....
  30. pmc Sodium arsenite exposure inhibits AKT and Stat3 activation, suppresses self-renewal and induces apoptotic death of embryonic stem cells
    Vladimir N Ivanov
    Department of Radiation Oncology, Center for Radiological Research, College of Physicians and Surgeons, Columbia University, 630 West 168th Street, New York, NY 10032, USA
    Apoptosis 18:188-200. 2013
    ....
  31. pmc Induction of apoptotic death and retardation of neuronal differentiation of human neural stem cells by sodium arsenite treatment
    Vladimir N Ivanov
    Center for Radiological Research, Department of Radiation Oncology, College of Physicians and Surgeons, Columbia University, 630 West 168th Street, NY 10032, USA
    Exp Cell Res 319:875-87. 2013
    ..Sodium arsenite also negatively affects neuronal differentiation of NSC through overactivation of MEK-ERK and suppression of PI3K-AKT...
  32. ncbi Radon-induced alterations in micro-RNA expression profiles in transformed BEAS2B cells
    Feng Mei Cui
    Department of Radiation Toxicology and Oncology, Beijing Institute of Radiation Medicine, Beijing, China
    J Toxicol Environ Health A 76:107-19. 2013
    ....
  33. pmc Radiation induced COX-2 expression and mutagenesis at non-targeted lung tissues of gpt delta transgenic mice
    Y Chai
    Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY, USA
    Br J Cancer 108:91-8. 2013
    ..Although radiation-induced bystander effects have been confirmed using a variety of endpoints, the mechanism(s) underlying these effects are not well understood, especially for in vivo study...
  34. pmc Radiation induced non-targeted response: mechanism and potential clinical implications
    Tom K Hei
    Center for Radiological Research, Department of Radiation Oncology, Columbia University Medical Center, Vanderbilt Clinic, New York, USA
    Curr Mol Pharmacol 4:96-105. 2011
    ..A better understanding of the mechanism of the non-targeted effects will be invaluable to assess its clinical relevance and ways in which the bystander phenomenon can be manipulated to increase therapeutic gain in radiotherapy...
  35. pmc A new view of radiation-induced cancer
    I Shuryak
    Center for Radiological Research, Columbia University, New York, NY 10032, USA
    Radiat Prot Dosimetry 143:358-64. 2011
    ..These results suggest that the combined short-long-term approach is a potentially promising method for predicting radiogenic cancer risks and interpreting the underlying biological mechanisms...
  36. pmc Mechanism of genotoxicity induced by targeted cytoplasmic irradiation
    M Hong
    Center for Radiological Research, Department of Radiation Oncology, College of Physicians and Surgeons, Columbia University Medical Center, 630 West 168th Street, New York, NY 10032, USA
    Br J Cancer 103:1263-8. 2010
    ..Although targeted cytoplasmic irradiation has been shown to induce mutations in mammalian cells, the precise mechanism(s) underlying the mutagenic process is largely unknown...
  37. pmc Resveratrol sensitizes melanomas to TRAIL through modulation of antiapoptotic gene expression
    Vladimir N Ivanov
    Center for Radiological Research, Columbia University, New York, NY 10032, USA
    Exp Cell Res 314:1163-76. 2008
    ..Taken together, these results suggest that resveratrol, in combination with TRAIL, may have a significant efficacy in the treatment of human melanomas...
  38. pmc Mitochondrial function and nuclear factor-kappaB-mediated signaling in radiation-induced bystander effects
    Hongning Zhou
    Center for Radiological Research, College of Physicians and Surgeons, Mailman School of Public Health, Columbia University, New York, NY, USA
    Cancer Res 68:2233-40. 2008
    ....
  39. ncbi Radiosensitization of melanoma cells through combined inhibition of protein regulators of cell survival
    Geoffrey E Johnson
    Center for Radiological Research, Columbia University, VC11 236, 630 West 168th Street, New York, NY 10032, USA
    Apoptosis 13:790-802. 2008
    ..Hence, surface expression of TRAIL induced by resveratrol appears to be a decisive event, one which determines an apoptotic versus a necrotic response of melanoma cells to sequential treatment...
  40. pmc Mitochondria-dependent signalling pathway are involved in the early process of radiation-induced bystander effects
    S Chen
    Key Laboratory of Ion Beam Bioengineering, Institute of Plasma Physics, Chinese Academy of Sciences, Hefei 230031, People s Republic of China
    Br J Cancer 98:1839-44. 2008
    ....
  41. ncbi Histone H2AX is a critical factor for cellular protection against DNA alkylating agents
    J A Meador
    Department of Radiation Oncology, College of Physicians and Surgeons, Center for Radiological Research, Columbia University Medical Center, New York, NY 10032, USA
    Oncogene 27:5662-71. 2008
    ..Therefore, targeting either PARP-1 or histone H2AX may provide an effective way of maximizing the chemotherapeutic value of alkylating agents for cancer treatment...
  42. pmc Development of gene expression signatures for practical radiation biodosimetry
    Sunirmal Paul
    Center for Radiological Research, Columbia University Medical Center, New York, NY 10032, USA
    Int J Radiat Oncol Biol Phys 71:1236-1244. 2008
    ..This approach could provide both an estimate of physical radiation dose and an indication of the extent of individual injury or future risk...
  43. ncbi Mechanism of radiation-induced bystander effects: a unifying model
    Tom K Hei
    Center for Radiological Research, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
    J Pharm Pharmacol 60:943-50. 2008
    ....
  44. pmc Expanding the question-answering potential of single-cell microbeams at RARAF, USA
    Alan Bigelow
    Center for Radiological Research, Columbia University, Irvington, New York 10533 0021, USA
    J Radiat Res 50:A21-8. 2009
    ..Additionally, an update on the status of the other biology oriented microbeams in the Americas is provided...
  45. ncbi Biophysical models of radiation bystander effects: 1. Spatial effects in three-dimensional tissues
    Igor Shuryak
    Center for Radiological Research, Columbia University Medical Center, New York, New York 10032, USA
    Radiat Res 168:741-9. 2007
    ..These assumptions are implemented by a mathematical formalism and computational algorithms. The model adequately describes data on bystander responses in the 3D system using a small number of adjustable parameters...
  46. ncbi Functional genomics in radiation biology: a gateway to cellular systems-level studies
    Sally A Amundson
    Center for Radiological Research, Columbia University Medical Center, 630 W 168th St, New York, NY 10032, USA
    Radiat Environ Biophys 47:25-31. 2008
    ..The future development of "integromic" models of radiation response should add substantially to the understanding gained from gene expression studies alone...
  47. ncbi Growth factor biomarkers associated with estrogen- and radiation-induced breast cancer progression
    G M Calaf
    Biology and Health Department, Faculty of Science, Tarapaca University, Arica, Chile
    Int J Oncol 28:87-93. 2006
    ....
  48. ncbi Allelic imbalance at 11q23-q24 chromosome associated with estrogen and radiation-induced breast cancer progression
    D Roy
    Center for Radiological Research, College of Physicians and Surgeons, Columbia University, New York, NY 11973, USA
    Int J Oncol 28:667-74. 2006
    ..It also represents the first indication of allele loss at these loci in human breast epithelial cells induced by radiation and estrogen treatment suggesting a potential interventional target in breast carcinogenesis...
  49. ncbi Cyclooxygenase-2 as a signaling molecule in radiation-induced bystander effect
    Tom K Hei
    Center for Radiological Research, College of Physicians and Surgeons, and Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, New York 10032, USA
    Mol Carcinog 45:455-60. 2006
    ....
  50. ncbi Radiation-induced leukemia at doses relevant to radiation therapy: modeling mechanisms and estimating risks
    Igor Shuryak
    Center for Radiological Research, Columbia University Medical Center, 630 West 168th St, New York, NY 10032, USA
    J Natl Cancer Inst 98:1794-806. 2006
    ..This earlier model predicted the risks of solid tumors induced by radiation therapy but overestimated the corresponding leukemia risks...
  51. ncbi DNA double-strand breaks form in bystander cells after microbeam irradiation of three-dimensional human tissue models
    Olga A Sedelnikova
    Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA
    Cancer Res 67:4295-302. 2007
    ..Thus, this study points to the importance of considering the indirect biological effects of radiation in cancer risk assessment...
  52. ncbi Sequential treatment by ionizing radiation and sodium arsenite dramatically accelerates TRAIL-mediated apoptosis of human melanoma cells
    Vladimir N Ivanov
    Center for Radiological Research, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA
    Cancer Res 67:5397-407. 2007
    ..These data highlight the efficacy of combined modality treatment involving radiation and arsenite in clinical management of this often fatal form of skin cancer...
  53. ncbi Demonstration of a radiation-induced bystander effect for low dose low LET beta-particles
    Rudranath Persaud
    Center for Radiological Research, Columbia University Medical Center, New York, NY 10032, USA
    Radiat Environ Biophys 46:395-400. 2007
    ..The results of this study will address the relevant issues of actual target size and radiation quality, and are likely to have a significant impact on our current understanding of radiation risk assessment...
  54. ncbi The complete nucleotide sequence of Chinese hamster (Cricetulus griseus) mitochondrial DNA
    Michael A Partridge
    College of Physicians and Surgeons, Center for Radiological Research, Columbia University, New York, NY 10032, USA
    DNA Seq 18:341-6. 2007
    ..We have obtained here the entire 16,284 bp sequence of the Chinese hamster mitochondrial genome, which will enable detailed analysis of mtDNA mutations caused by exposure to mutagens in hamster-derived cell lines...
  55. pmc Microbeam irradiation of the C. elegans nematode
    Antonella Bertucci
    Center for Radiological Research, Columbia University Medical Center, New York, NY 10032, USA
    J Radiat Res 50:A49-54. 2009
    ..GFP expression was enhanced after 24 hours in a number dependent manner at distances > 100 microm from the site of irradiation...
  56. pmc Consequences of cytoplasmic irradiation: studies from microbeam
    Hongning Zhou
    Center for Radiological Research, Columbia University Medical Center, 630 West 168th Street, New York, NY 10032, USA
    J Radiat Res 50:A59-65. 2009
    ..This review will summarize the biological responses after cytoplasm irradiated by microbeam, and the possible mechanisms involved in cytoplasmic irradiation...
  57. pmc DNA-dependent protein kinase (DNA-PK)-deficient human glioblastoma cells are preferentially sensitized by Zebularine
    Jarah A Meador
    Center for Radiological Research, Department of Radiation Oncology, Columbia University Medical Center, New York, NY 10032, USA
    Carcinogenesis 31:184-91. 2010
    ..Collectively, our study suggests that DNA-PK is the major determining factor for cellular response to Zebularine...
  58. pmc Biodosimetry on small blood volume using gene expression assay
    Muriel Brengues
    Applied NanoBioscience Center and Medicine, University of Arizona, Phoenix, AZ 85004 2157, USA
    Health Phys 98:179-85. 2010
    ..The scalability characteristics of the assay make it appropriate for population triage. This biodosimetry platform could also be used for personalized monitoring of radiotherapy treatments received by patients...
  59. pmc Radiation-induced bystander signaling pathways in human fibroblasts: a role for interleukin-33 in the signal transmission
    Vladimir N Ivanov
    Center for Radiological Research, Department of Radiation Oncology, Columbia University, New York, NY 10032, USA
    Cell Signal 22:1076-87. 2010
    ....
  60. pmc High-throughput antibody-based assays to identify and quantify radiation-responsive protein biomarkers
    Michael A Partridge
    Center for Radiological Research, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA
    Int J Radiat Biol 86:321-8. 2010
    ..However, only a fraction of those individuals will need urgent medical attention. Consequently, a rapid screening test is needed to identify those people who require immediate treatment...
  61. pmc Disruption of IGF-1R signaling increases TRAIL-induced apoptosis: a new potential therapy for the treatment of melanoma
    Thomas B Karasic
    Center for Radiological Research, Department of Radiation Oncology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
    Exp Cell Res 316:1994-2007. 2010
    ..The ultimate goal of this direction of research is the discovery of a new treatment method for highly resistant human metastatic melanomas. Our findings provide the rationale for further preclinical evaluation of this novel treatment...
  62. ncbi Effects of radiation quality on interactions between oxidative stress, protein and DNA damage in Deinococcus radiodurans
    Igor Shuryak
    Center for Radiological Research, Columbia University Medical Center, New York, NY 10032, USA
    Radiat Environ Biophys 49:693-703. 2010
    ..These results suggest that synergism between oxidative stress and DNA damage may play an important role not only during γ-ray exposure, but during high-LET radiation exposure as well...
  63. pmc Regulation of early signaling and gene expression in the alpha-particle and bystander response of IMR-90 human fibroblasts
    Shanaz A Ghandhi
    Center for Radiological Research, Columbia University, VC11 215, 630 West 168th Street, New York, NY 10032, USA
    BMC Med Genomics 3:31. 2010
    ....
  64. pmc The role of mass spectrometry-based metabolomics in medical countermeasures against radiation
    Andrew D Patterson
    Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA
    Mass Spectrom Rev 29:503-21. 2010
    ....
  65. ncbi Extrapolating radiation-induced cancer risks from low doses to very low doses
    David J Brenner
    Center for Radiological Research, Columbia University Medical Center, 630 West 168th Street, New York, NY 10032, USA
    Health Phys 97:505-9. 2009
    ....
  66. pmc Advances in radiobiological studies using a microbeam
    Tom K Hei
    Center for Radiological Research, Mailman School of Public Health, Columbia University, New York, NY 10032, USA
    J Radiat Res 50:A7-A12. 2009
    ..The identification of specific signaling pathways provides mechanistic insight on the nature of the bystander process...
  67. pmc Inhibition of ataxia telangiectasia mutated kinase activity enhances TRAIL-mediated apoptosis in human melanoma cells
    Vladimir N Ivanov
    Center for Radiological Research, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA
    Cancer Res 69:3510-9. 2009
    ..Taken together, our data show the existence of an ATM-dependent STAT3-mediated antiapoptotic pathway, which on suppression sensitizes human melanoma cells to TRAIL-mediated apoptosis...
  68. pmc A new view of radiation-induced cancer: integrating short- and long-term processes. Part II: second cancer risk estimation
    Igor Shuryak
    Center for Radiological Research, Columbia University Medical Center, New York, NY 10032, USA
    Radiat Environ Biophys 48:275-86. 2009
    ..Potentially, the model can be incorporated into radiotherapy treatment planning algorithms, adding second cancer risk as an optimization criterion...
  69. pmc A new view of radiation-induced cancer: integrating short- and long-term processes. Part I: approach
    Igor Shuryak
    Center for Radiological Research, Columbia University Medical Center, New York, NY 10032, USA
    Radiat Environ Biophys 48:263-74. 2009
    ....
  70. pmc Protein kinase C epsilon is involved in ionizing radiation induced bystander response in human cells
    Burong Hu
    Center for Radiological Research, Department of Radiation Oncology, College of Physicians and Surgeons, 630 West, 168th Street, VC 11, Room 239, Columbia University, New York, NY 10032, USA
    Int J Biochem Cell Biol 41:2413-21. 2009
    ..Our novel study suggests the possibility that PKC signaling pathway may be a critical molecular target for suppression of ionizing radiation induced biological effects in bystander cells...
  71. pmc Analysis of ionizing radiation-induced DNA damage and repair in three-dimensional human skin model system
    Yanrong Su
    Department of Radiation Oncology, College of Physicians and Surgeons, Columbia University Medical Center, New York, NY 10032, USA
    Exp Dermatol 19:e16-22. 2010
    ..In summary, we have successfully demonstrated the feasibility of monitoring the DNA damage response in human skin tissue microenvironment. In this system, 53BP1 can be used as a useful marker for monitoring the DSB repair efficiency...
  72. pmc A model of interactions between radiation-induced oxidative stress, protein and DNA damage in Deinococcus radiodurans
    Igor Shuryak
    Center for Radiological Research, Columbia University Medical Center, 630 West 168th St, New York, NY 10032, USA
    J Theor Biol 261:305-17. 2009
    ..Our model of radiogenic oxidative stress is consistent with these data and can potentially be generalized to other organisms and lower radiation doses...
  73. pmc Reduction of the secondary neutron dose in passively scattered proton radiotherapy, using an optimized pre-collimator/collimator
    David J Brenner
    Center for Radiological Research, Columbia University Medical Center, 630 West 168th Street, New York, NY 10032, USA
    Phys Med Biol 54:6065-78. 2009
    ....
  74. ncbi Quantification of CD59- mutants in human-hamster hybrid (AL) cells by flow cytometry
    Hongning Zhou
    Center for Radiological Research, College of Physicians and Surgeons, Vanderbilt Clinic 11 201, Columbia University Medical Center, 630 West 168th Street, New York, NY 10032, USA
    Mutat Res 594:113-9. 2006
    ....