Bystander effect induced changes in apoptosis related proteins and terminal differentiation in in vitro murine bladder cultures

Purpose: Radiation-induced bystander effects are now an established phenomenon seen in numerous cell and tissue culture models. The aim of this investigation was to examine the bystander signal and response in a multicellular primary tissue culture system in vitro. Methods and materials: Murine bladder samples were explanted and directly exposed to gamma radiation, or treated with irradiated tissue conditioned medium (ITCM) generated from the directly irradiated cultures. Results: Results indicated that there was a strong bystander signal produced by the tissue that caused both dose-dependent and -independent changes in the ITCM treated tissue. Significantly increased B-cell lymphoma 2 (Bcl2) expression was noted after treatment with 0.5Gy and 5Gy ITCM (approximately 80%), while dose-dependent changes were observed in c-myelocytomatosis (cMyc) (39.48% at 0.5 Gy ITCM, 81.28% at 5 Gy ITCM) and the terminal differentiation marker uroplakin III (17.88% at 0.5 Gy). Nuclear fragmentation was also significantly increased at both doses of ITCM. Conclusion: These data suggest that the bystander signal produced in a multicellular environment induces complex changes in the ITCM-treated culture, and that these changes are reflective of a coordinated response to maintain integrity throughout the tissue.

[1]  C. Mothersill,et al.  Bystander-induced differentiation: a major response to targeted irradiation of a urothelial explant model. , 2006, Mutation research.

[2]  J. Little.  Cellular radiation effects and the bystander response. , 2006, Mutation research.

[3]  C. Mothersill,et al.  Radiation-induced bystander effects and the DNA paradigm: an "out of field" perspective. , 2006, Mutation research.

[4]  C. Mothersill,et al.  The Involvement of Calcium and MAP Kinase Signaling Pathways in the Production of Radiation-Induced Bystander Effects , 2006, Radiation research.

[5]  C. Mothersill,et al.  Apoptosis is initiated in human keratinocytes exposed to signalling factors from microbeam irradiated cells , 2006, International journal of radiation biology.

[6]  David J Brenner,et al.  Biological effects in unirradiated human tissue induced by radiation damage up to 1 mm away. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[7]  Giuseppe Schettino,et al.  New insights on cell death from radiation exposure. , 2005, The Lancet. Oncology.

[8]  C. Mothersill,et al.  Medium from Irradiated Cells Induces Dose-Dependent Mitochondrial Changes and BCL2 Responses in Unirradiated Human Keratinocytes , 2005, Radiation research.

[9]  C. Mothersill,et al.  Genetic Factors Influencing Bystander Signaling in Murine Bladder Epithelium after Low-Dose Irradiation In Vivo , 2005, Radiation research.

[10]  E. Wright,et al.  Damaging and protective cell signalling in the untargeted effects of ionizing radiation. , 2004, Mutation research.

[11]  M. Suzuki,et al.  Effect of Medium on Chromatin Damage in Bystander Mammalian Cells , 2004, Radiation research.

[12]  K. Prise,et al.  Nitric oxide-mediated signaling in the bystander response of individually targeted glioma cells. , 2003, Cancer research.

[13]  Colin Seymour,et al.  Radiation-induced bystander effects, carcinogenesis and models , 2003, Oncogene.

[14]  W. Morgan.  Is there a common mechanism underlying genomic instability, bystander effects and other nontargeted effects of exposure to ionizing radiation? , 2003, Oncogene.

[15]  K M Prise,et al.  A review of the bystander effect and its implications for low-dose exposure. , 2003, Radiation protection dosimetry.

[16]  C. Mothersill,et al.  A proliferation-dependent bystander effect in primary porcine and human urothelial explants in response to targeted irradiation , 2003, British Journal of Cancer.

[17]  G. Fiskum,et al.  Effect of Bcl-2 Overexpression on Mitochondrial Structure and Function* , 2002, The Journal of Biological Chemistry.

[18]  K M Prise,et al.  Bystander-induced apoptosis and premature differentiation in primary urothelial explants after charged particle microbeam irradiation. , 2002, Radiation protection dosimetry.

[19]  C. Mothersill,et al.  Characterisation of a bystander effect induced in human tissue explant cultures by low let radiation. , 2002, Radiation protection dosimetry.

[20]  J. Little,et al.  Bystander effects: intercellular transmission of radiation damage signals. , 2002, Radiation protection dosimetry.

[21]  Reprints and Subscriptions Permissions , 2003 .

[22]  E. Wright,et al.  Inflammatory-type responses after exposure to ionizing radiation in vivo: a mechanism for radiation-induced bystander effects? , 2001, Oncogene.

[23]  C. Mothersill,et al.  Individual variation in the production of a 'bystander signal' following irradiation of primary cultures of normal human urothelium. , 2001, Carcinogenesis.

[24]  Carmel Mothersill,et al.  Radiation-Induced Bystander Effects: Past History and Future Directions , 2001, Radiation research.

[25]  Ken Ohnishi,et al.  Induction of Radioresistance by a Nitric Oxide-Mediated Bystander Effect , 2001, Radiation research.

[26]  A. Bishayee,et al.  Free Radical-Initiated and Gap Junction-Mediated Bystander Effect due to Nonuniform Distribution of Incorporated Radioactivity in a Three-Dimensional Tissue Culture Model , 2001, Radiation research.

[27]  N. Dainiak,et al.  Ionizing Radiation Alters Fas Antigen Ligand at the Cell Surface and on Exfoliated Plasma Membrane-Derived Vesicles: Implications for Apoptosis and Intercellular Signaling , 2000, Radiation research.

[28]  C. Mothersill,et al.  Identification and characterization of three subtypes of radiation response in normal human urothelial cultures exposed to ionizing radiation. , 1999, Carcinogenesis.

[29]  K. Zeller,et al.  Function of the c-Myc oncogenic transcription factor. , 1999, Experimental cell research.

[30]  K M Prise,et al.  Studies of bystander effects in human fibroblasts using a charged particle microbeam. , 1998, International journal of radiation biology.

[31]  Y. Tsujimoto,et al.  Bcl-2 prevents apoptotic mitochondrial dysfunction by regulating proton flux. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[32]  B. Lehnert,et al.  Alpha particles initiate biological production of superoxide anions and hydrogen peroxide in human cells. , 1997, Cancer research.

[33]  E H Goodwin,et al.  Extracellular factor(s) following exposure to alpha particles can cause sister chromatid exchanges in normal human cells. , 1997, Cancer research.

[34]  E. Wright,et al.  Long-term in vivo transmission of alpha-particle-induced chromosomal instability in murine haemopoietic cells. , 1996, International journal of radiation biology.

[35]  J. Little,et al.  Induction of sister chromatid exchanges by extremely low doses of alpha-particles. , 1992, Cancer research.

[36]  J. DiPaolo,et al.  Continuous cell lines with altered growth and differentiation properties originate after transfection of human keratinocytes with human papillomavirus type 16 DNA. , 1988, Carcinogenesis.

[37]  J. Hollowell,et al.  Chromosome Damage Induced by Plasma of X-Rayed Patients , 1968, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[38]  J. Souto.  Tumour Development in the Rat induced by Blood of Irradiated Animals , 1962, Nature.

[39]  T. Puck,et al.  ACTION OF X-RAYS ON MAMMALIAN CELLS , 1957, The Journal of experimental medicine.

[40]  D. Childs,et al.  Changes in sternal marrow following roentgen‐ray therapy to the spleen in chronic granulocytic leukemia , 1954, Cancer.