Columbia University Medical Center
Center for Radiological Research

NIH Program Project on
Radiation Bystander Effects: Mechanism
PO1-CA 49062-23

Recent Publications that are supported either fully or partially by the Program Project (2009-present):

  1. *Ivanov, VN., Zhou, HZ., Ghandhi, SA., Karasic, TB., Yaghoubian, B., Amundson, S.., and Hei, TK. (2010) Radiation induced bystander signaling pathways in human fibroblasts: A role for interleukin 33 in the signaling transmission. Cell Signaling 22: 1076-1087. PMCID: PMC2860693

  2. *Ghandhi, S.A., Ming, L., Ivanov, V., Hei, TK., Amundson, SA. (2010) Regulation of early signaling and gene expression in the alpha particle and bystander response of IMR-90 human fibroblasts. BMC Med. Genomics Jul 29:3:31. PMCID: PMC2919438

  3. Hong, M., Xu, A., Zhou, HN., Wu, L., Randers-Pehron, G., Santella, R., Yu, Z., and Hei, TK. (2010) Mechanism of genotoxicity induced by targeted cytoplasmic irradiation. Brit. J. Cancer 103: 1263-1268. PMCID: PMC2967061

  4. Ende, NE., and Azzam, EI. (2010) Planning for the Treatment of Mass Casualties Based on Pathology of the Fatalities of Hiroshima and Nagasaki. International Journal of Radiation Biology 87(4): 443-444. PMID: 21204615. PMCID: pending. NIHMSID: 584167

  5. Lieberman HB, Bernstock JD, Broustas CG, Hopkins KM, Leloup C, Zhu A. (2011) The role of RAD9 in tumorigenesis. J Mol Cell Biol. 3: 39-43. PMCID: PMC3107465

  6. Ivanov, V., Partridge, MA., Huang, S. and Hei, TK. (2011) Suppression of the proinflammatory response of metastastic melanoma cells increases TRAIL-induced apoptosis. J. Cell. Biochem. 112: 463-475. PMID 21268068. PMCID: PMC4378843

  7. Hei, T.K., Zhou, H.N., Yunfei, C., Ponnaiya, B., and Ivanov, V. (2011) Radiation induced non-targeted response: mechanism and potential clinical implications. Current Molecular Pharmacology 4:96-105. PMCID: PMC3356574

  8. *Ivanov, VN., Ghandhi, SA., Zhou, H., Huang, SX., Chai, Y., Amundson, SA, Hei, TK.(2011) Radiation response and regulation of apoptosis induced by a combination of TRAIL and CHX in cells lacking mitochondrial DNA: A role for NF-?B-STAT3-directed gene expression. Exp. Cell Res. 317: 1548-1566. PMCID: PMC3725824

  9. Ponnaiya, B., Suzuki, M., Tsuruoka, C. Uchihori, Y., Wei, Y. and Hei, TK. (2011) Detection of chromosomal instability in bystander cells after Si490 ion irradiation. Radiat. Res. 176:280-290. PMCID: PMC3186077

  10. Hei, TK., Zhao, Y., Zhou, HZ., and Ivanov, I. (2011) Mechanism of Radiation Carcinogenesis: Role of the TGFBI gene and the inflammatory signaling pathway. Adv. Exp. Med. Biol. 720: 163-170. PMID: 21901626. PMCID: pending

  11. Wen, G., Partridge, MA., Li, B., Hong, M., Liao, W., Cheng, SK., Zhao, Y., Calaf, GM., Liu, T., Zhou, J., Zhang, Z., and Hei, TK (2011) TGFBI expression reduces in vitro and in vivo metastatic potential of lung and breast tumor cells. Cancer Letter. 308:23-32. PMCID: PMC3167173

  12. Wen, G., Hong M., Li, B., Liao, W. Cheng, SK., Hu, B., Calaf, C. M., Lu, P., Partridge, MA., Tong, J. and Hei, TK. (2011) Transforming growth factor-B induced protein suppresses mesothelioma progression through the Akt/mTOR pathway. Int. J. Oncology 39:1001-1009. PMID: 21701776. PMCID: PMC4090925

  13. Autsavapromporn,N., de Toledo, SM., Little, JB., Jay-Gerin, JP., Harris, AL. and Azzam, EI. (2011) The Role of Gap-Junction Communication and Oxidative Stress in the Propagation of Toxic Effects among High Dose Particle-Irradiated Human Cell. Radiation Research 175, 347-357. PMCID: PMC 3139025

  14. Buonanno, M., de Toledo, SM., Pain,D., and Azzam, EI. (2011) Long-Term Consequences of Radiation-Induced Bystander Effects Depend on Radiation Quality and Dose and Correlate with Persistent Oxidative Stress. Radiation Research 175(4): 405-415. PMCID: PMC3106980

  15. de Toledo SM, Buonanno M, Li M, Asaad N, Qin Y, Gonon G, Shim G, Galdass M, Boateng Y, Zhang J, Azzam EI. (2011) The impact of adaptive and non-targeted effects in the biological responses to low dose/ low fluence ionizing radiation: the modulating effect of linear energy transfer. Health Physics 100(3):290-292. PMCID: PMC3078715

  16. Autsavapromporn, N., deToledo, SM., Buonanno, M., Jay-Gerin, JP., Harris, AL. and Azzam, EI. (2011) Intercellular Communication Amplifies Stressful Effects in HZE Particle-Irradiated Human Cells. Journal of Radiation Research 52:408-414. PMID: 21905305. PMCID: PMC4058820

  17. Zhang, J., Buonanno, M., Gonon,G., Li, M., Galdass, M., Shim, G., de Toledo, SM. and Azzam, EI. Bystander Effects and Adaptive Responses Modulate In Vitro and In Vivo Biological Responses to Low Dose Ionizing Radiation. A chapter in "Radiobiological Issues Pertaining to Environmental Security and Ecoterrorism" (Carmel Mothersill, Editor). NATO Science for Peace and Security Series C: Environmental Security. Springer (2011).

  18. Buonanno, M., de Toledo, S. and Azzam, EI. (2011) Increased Frequency of Spontaneous Neoplastic Transformation in Progeny of Bystander Cells from Cultures Exposed to Densely-Ionizing Radiation. PLoS ONE 6 (6) e21540. PMCID: PMC3125249

  19. Azzam, EI. (2011) Exposure to low level environmental agents: The induction of hormesis. Mutation Research, 726(2), 89-90. PMID: 21807115. PMCID: PMC4518538

  20. Azzam, EI., Jay-Gerin, J. P., and Pain, D (2011) Ionizing radiation-induced metabolic oxidative stress and prolonged cell injury. Cancer Letter 327:48-60. PMCID: PMC3980444

  21. Ghandhi, SA., Sinha, A., Markatou, M. and Amundson, SA (2011) Time series clustering of gene expression in irradiated and bystander fibroblasts: An application of FBPA clustering. BMC Genomics 12:2. PMCID: PMC 3022823.

  22. Ende, NE., Kovalenko, OA., and Azzam, EI. (2011) The necessity of the early use of antibiotics in treatment of mass casualties from ionizing radiation. Int. J. Radiation Biol. 88:381-387. PMCID: PMC4036676.

  23. Broustas, CG., Lieberman, HB (2012) Contributions of Rad9 to tumorigenesis. J Cell Biochem. 113:742-51. PMCID: PMC3264844

  24. Broustas, CG., Zhu, A., and Lieberman, HB (2012) Rad9 contributes to prostate tumor progression by promoting cell migration and anoikis resistance. J. Biol. Chem. 287:41324-41333. PMCID: PMC3510830

  25. *Hu, B., Grabham, PN., Balajee, AS., Zhou, H., Hei, TK., and Geard, CR.(2012) Intrachromosomal changes and genomic instability in site-specific microbeam irradiated and bystander human hamster hybrid cells. Radiat. Res. 177: 25-34. PMCID: PMC3410536

  26. Yang, G., Wang, Y., Fu, W., Wu, J. Mei, T., Li, J. Tang, Y, Luo, C., Ouyang, Q., Chen, S., Wu, L. Hei, TK. and Wang, Y. (2012) Dynamic equilibrium between cancer stem cells and non-stem cells in human SW620 and MCF-7 cancer cell populations. Brit. J. Cancer 106:1512-1519. PMCID: PMC 3341854

  27. *Haung, SX., Partridge, MA., Ghandhi, SA., Davidson, MM., Amundson, SA., and Hei, TK. (2012) Mitochondrial derived reactive intermediate species mediated asbestos induced genotoxicity and oxidative stress-responsive signaling pathways. Environ. Hlth. Perspect. 120:840-847. PMCID: PMC 3385428

  28. Li, BY., Wei, H., Cheng, YZ., Xue, L. Wang, AQ., Hei, TK., and Tong, J. (2012) Radon induced reduced apoptosis in human bronchial epithelial cells with knockdown of mitochondrial DNA. J. Toxicol. Environ. Hlth., 75:1111-1119. PMCID: PMC 3518846

  29. *Zhang, S., Wen, G., Huang, SX., Wang, J., Tong, J. and Hei, TK. (2012) Mitochondrial alterations in malignantly transformed human small airway epithelial cells induced by alpha particles. Int. J. Cancer 132: 19-28. PMCID: PMC 3467313

  30. Azzam, EI., Jay-Gerin, J., and Pain, D. (2012) Ionizing radiation-induced metabolic oxidative stress and prolonged cell injury. Cancer Letters 327:48-60. PMCID: PMC3980444

  31. Zhang, J., de Toledo, SM., Pandey, BN., Guo, G., Pain, D., Li, H. and Azzam, EI.(2012) Role of the Translationally Controlled Tumor Protein in DNA Damage Sensing and Repair. Proc. Natl. Acad. Sci. (USA) 109: 926-933. PMCID: PMC3341051

  32. Chaudhry, AM., Omaruddin, RA., Kreger, B., de Toledo, SM., and Azzam, SI. (2012) Micro RNA Responses to Chronic or Acute Exposures to Low Doses of Ionizing Radiation. Molecular Biology Reports 39: 7549-7558. PMID:22367372. PMCID: PMC4062182

  33. Akudugu, JM., Azzam, EI., and Howell, RW. (2012) Induction of Bystander Cell Killing in Human Breast Cancer Cell Cultures by DNA-Incorporated Iodine-125 Depends on Phenotype. International Journal of Radiation Biology 88:1028-1038. PMID: 22489958. PMCID: PMC4029165

  34. *Chai, Y., Calaf, G.M., Zhou, H. Ghandhi, SA., Elliston, CD., Wen, G., Nohmi, T., Amundson, S. and Hei, TK. (2013). Radiation induced COX-2 expression and mutagenesis at non-targeted lung tissues of gpt delta transgenic mice. British J. Cancer 108: 91-98. PMCID: PMC 3553512

  35. Ivanov, VN. and Hei, TK. (2013) Induction of apoptotic death and retardation of neuronal differentiation of human neural stem cells by sodium arsenite treatment. Exp. Cell Res. 319: 875-887. PMCID: PMC 3593966

  36. Ivanov, VN., Wen, G., and Hei, TK. (2013) Sodium arsenite exposure inhibits AKT and Stat-3 activation, suppresses self renewal and induces apoptotic death of embryonic stem cells. Apoptosis 18:188-200. PMCID: PMC 3552097

  37. *Chai, Y., Lam, RK., Calaf, G. M., Zhou, H., Amundson, S., and Hei, TK., (2013) Radiation-induced non-targeted response in vivo: role of the TGF?-TGFBR1-COX-2 signaling pathway. Brit. J. Cancer 108: 1106-1112. PMCID: PMC 3619070

  38. Hu, B., Zhu, J., Zhou, H., and Hei, TK. (2013) No significant level of inheritable interchromosomal aberrations in the progeny of bystander primary human fibroblast after alpha particle irradiation. Adv. Space Research 51:450-457. PMCID: PMC 3596834

  39. Zhang, B., Davidson, MM., Zhou, HZ,, Wang, C., Walker, WF and Hei, T.K. (2013) Cytoplamic irradation results in mitochondrial dysfunciton and DRP-1 dependent mitochondrial fission. Cancer Research 73:6700-6710. PMCID: PMC3934017

  40. Gonon, G., Groetz, J., de Toledo, SM., Fromm, M. and Azzam, EI. (2013) Non-Targeted 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. Radiation Research 179: 444-457. PMCID: PMC3995407

  41. *Azzam, EI., de Toledo, SM., Harris, AL., Ivanov, V., Zhou, H., Amundson,SA., Lieberman, HB., and Hei, TK. (2013) The Ionizing Radiation-Induced Bystander Effect: Evidence, Mechanism and Significance in 'Pathobiology of Cancer Regimen-Related Toxicities', Stephen T. Sonis and Dorothy M. Keefe, Editors; Springer, New York, NY.; pp.42-68.

  42. Autsavapromporn, N., de Toledo, SM., Jay-Gerin, J., Harris, AL. and Azzam, EI. (2013) Human Cell Responses to Ionizing Radiation are Differentially Affected by the Expressed Connexins. Journal of Radiation Research (Tokyo) 54(2):251-9. PMCID: PMC3589937.

  43. Kovalenko, OA., Azzam, EI., and Ende, NE (2013) Human Umbilical Cord Blood Mononucleated Cells Enhance the Survival of Lethally Irradiated Mice: Dosage and the Window of Time. Journal of Radiation Research (Tokyo) 54 (6): 1010-1014. PMCID: PMC3823783.

  44. Li, M., Gonon,G., Buonanno, M., Autsavapromporn, N., de Toledo, SM., Pain, D., and Azzam, EI. (2013) Health Risks of Space Exploration: Targeted and Non-targeted Oxidative Injury by High Charge and High Energy Particles. Antioxidants and Redox Signaling 20(9): 1501-1523. PMCID: PMC3936510.

  45. *Autsavapromporn, N., Suzuki, M., Funayama, T., Usami, U., Plante, I., Yokota, Y., Mutou, Y., Ikeda, H., Uchihori, Y., Kobayashi, K., Kobayashi, Y., Hei, TK., Azzam, EI. and Murakami, T (2013) Gap Junction Communication and the Propagation of Bystander Effect in induced by Microbeam Irradiation in Human Fibroblasts: The Impact of Radiation Quality, Radiation Research 180: 367-375. PMID: 23987132. PMCID: PMC4058832

  46. *Autsavapromporn, N., Suzuki M., Plante I., Liu C., Uchihori Y., Hei TK., Azzam EI. and Murakami T. (2013) Participation of Gap Junction Communication in Potentially Lethal Damage Repair and DNA Damage in Human Fibroblasts Exposed to Low-or High-LET Radiation, Mutation Research 756:78-85. PMCID: PMC4001089

  47. Ivanov, VN. and Hei, TK. (2014) A role of TRAIL/TRAIL-R2 in radiation induced apoptosis and radiation induced bystander response of human neural stem cells. Apoptosis 19:399-413. PMCID: PMC3945673

  48. *Zhao, Y., deToledo, SM., Hu, G., Hei, TK., and Azzam, EI. (2014). Connexins and cyclooxygenase-2 cross talk in the expression of radiation induced bystander effects. Brit. J. Cancer 111:125-131. PMCID: PMC 4090739

  49. Shim, G., Ricoul, M., Hepel, W., Azzam, EI., and Sabatier, L (2014). Cross talk between telomere maintenance and radiation effects: A key player in the process of radiation induced carcinogenesis. Mutation Research- Review Jan 31. pii: S1383-5742(14)00002-7 doi: 10.1016/j.mrrev.2014.01.001. [Epub ahead of print] PMCID: PMC4119099

  50. Zhang, B., Davidson, MM., Hei, TK (2014). Mitochondria regulate DNA damage and genomic instability induced by high LET radiation. Life Sci Space Res (Amst). 1:80-88. PMCID: PMC4111269

  51. Gong, X., Ivanov, VN., Davidson, MM., Hei, TK (2014). Tetramethylpyrazine (TMP) protects against sodium arsenite-induced nephrotoxicity by suppressing ROS production, mitochondrial dysfunction, pro-inflammatory signaling pathways and programed cell death. Arch Toxicol. 2014 Jun 25. PMCID: PMC 4377316.

  52. Hu, W., Xu, S., Yao, B., Hong, M., Wu, X., Pei, H., Chang, L., Ding, N., Gao, X., Ye, C., Wang, J., Hei, TK., Zhou, G (2014). MiR-663 inhibits radiation-induced bystander effects by targeting TGFB1 in a feedback mode. RNA Biol. 11:1189-1198. PMID: 25483041

  53. *Ghandhi, SA., Ponnaiya, B., Panigrahi, SK., Hopkins, KM., Cui, Q., Hei, TK., Amundson, SA., Lieberman, HB (2014). RAD9 deficiency enhances radiation induced bystander DNA damage and transcriptomal response. Radiat Oncol. 2014 Sep 18;9:206. doi: 10.1186/1748-717X-9-206. PMCID: PMC4261775

  54. Broustas, CG., Lieberman, HB (2014). RAD9 enhances radioresistance of human prostate cancer cells through regulation of ITGB1 protein levels. Prostate 74:1359-1370. PMCID: PMC 4142073

  55. Ivanov, VN and Hei, TK (2014) Radiation-induced gliobloastoma signaling cascade regulates viability, apoptosis and differentiation of neural stem cells. Apoptosis Dec;19(12):1736-54. doi: 10.1007/s10495-014-1040-x. PMCID: PMC4378234

  56. *Xu Y, Zhang B, Messerli M, Randers-Pehrson G, Hei TK, Brenner DJ. 2015. Metabolic oxygen consumption measurement with a single-cell biosensor after particle microbeam irradiation. Radiat Environ Biophys. 54:137-144. PMCID: PMC 4378234

  57. Autsavapromporn, N., Plante, I., Liu, C., Konishi, K., Usami, N., Funayama, T., Azzam, EI., Murakami, K. and Suzuki, M. (2015) Genetic Changes in Progeny of Bystander Human Fibroblasts after Microbeam Irradiation with X rays, Protons or Carbon ions The Relevance to Cancer Risk. Int. J. of Radiat.Biol. 91 (1): 62-70. PMID: 25084840

  58. Buonanno, M., de Toledo, S., Howell, R and Azzam, EI. (2015) Low Dose Energetic Protons Induce Targeted and Bystander Effects that Protect Human Cells from the DNA Damaging Effects of a Subsequent Exposure to Energetic Iron Ions. J. Radiat. Res. 56(3):502-8. PMCID: PMC4426929

  59. Nicolas, F., Wu, C., Bukhari, S., de Toledo, S., Li, H., Shibata, M., and Azzam, EI. (2015) S-Nitrosylation in Organs of Mice Exposed to Low or High Doses of Rays: The Modulating Effect of Iodine Contrast Agent at Low Radiation Dose. Proteomes 3: 56-73. PMCID: PMC4548934

  60. Chen, H., Goodus, M., de Toledo, S., Azzam, EI., Levison, SW. and Souayah, N. (2015) Ionizing Radiation Perturbs Cell Cycle Progression of Neural Precursors in the Subventricular Zone without Affecting their Long-term Self-Renewal. ASN Neuro Jun 8;7(3). pii: 1759091415578026. doi: 10.1177/1759091415578026. PMCID: PMC4461572

  61. Dong, C., He, M., Konishi, T., Liu, W., Li, W., Uchihori, YH., Hei, TK., and Shao, C. (2015) The differential role of human macrophage in triggering secondary bystander effects after either gamma-ray or carbon ion irradiation. Cancer Letter 363:92-100. PMCID: PMC 4428931

  62. Wang, TJ., Wu, CC., Chai, Y., Lam, RK., Hamada, N., Kakinuma, S., Uchihori, Y., Yu, PK., Hei, TK (2015). Induction of Non-Targeted Stress Responses in Mammary Tissues by Heavy Ions. PLoS One Aug 28;10(8):e0136307. doi: 10.1371/journal.pone.0136307. PMCID: PMC4552651

* denotes joint publications between project and core leaders