Bystander signal production and response are independent processes which are cell line dependent

Purpose: Radiation-induced bystander effects are now an established phenomenon seen in numerous models; however it is not known whether the magnitude of the bystander effect is determined by the signal produced by the irradiated cells or the response of the exposed cells. The aim of this investigation is to determine the importance of the bystander signal versus the bystander response in three different cell line models. Methods: A matrix design experiment using cell lines, HPV-G, CHO-K1 and E89 (glucose 6-phosphate dehydrogenase (G6DP) null) was set up to produce irradiated cell conditioned medium (ICCM), which was used to treat all cell lines. Results: For HPV-G and CHO-K1 lines, the response to autologous ICCM was significantly different to that when treated with ICCM generated from another line. These lines displayed no response to E89 ICCM, nor did E89 cells show a significant response to any ICCM, suggesting that G6DP plays a key role in the bystander effect. Conclusion: These data suggest, for these cell lines at least, that in the case of cell lines capable of responding to the bystander signal, it is the signal produced by the irradiated cell that determines the magnitude of the bystander effect.

[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]  T. Hei,et al.  The time and spatial effects of bystander response in mammalian cells induced by low dose radiation. , 2006, Carcinogenesis.

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

[7]  Nesrin Asaad,et al.  Medium-mediated intercellular communication is involved in bystander responses of X-ray-irradiated normal human fibroblasts , 2005, Oncogene.

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

[9]  B. Vojnovic,et al.  Evidence for induction of DNA double strand breaks in the bystander response to targeted soft X-rays in CHO cells. , 2004, Mutation research.

[10]  C. Mothersill,et al.  Bystander Effects in Repair-Deficient Cell Lines , 2004, Radiation research.

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

[12]  G Schettino,et al.  Low-Dose Studies of Bystander Cell Killing with Targeted Soft X Rays , 2003, Radiation research.

[13]  J. Little,et al.  Oxidative metabolism, gap junctions and the ionizing radiation-induced bystander effect , 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]  S. Wada,et al.  Bystander effect induced by counted high‐LET particles in confluent human fibroblasts: a mechanistic study , 2003, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

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

[17]  Edouard I Azzam,et al.  Oxidative metabolism modulates signal transduction and micronucleus formation in bystander cells from alpha-particle-irradiated normal human fibroblast cultures. , 2002, Cancer research.

[18]  Rashi Iyer,et al.  Low dose, low-LET ionizing radiation-induced radioadaptation and associated early responses in unirradiated cells. , 2002, Mutation research.

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

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

[21]  L. Oberley,et al.  H2O2-induced O⨪2Production by a Non-phagocytic NAD(P)H Oxidase Causes Oxidant Injury* , 2001, The Journal of Biological Chemistry.

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

[23]  J. Little,et al.  Direct evidence for the participation of gap junction-mediated intercellular communication in the transmission of damage signals from alpha -particle irradiated to nonirradiated cells. , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[24]  C. Mothersill,et al.  Production of a signal by irradiated cells which leads to a response in unirradiated cells characteristic of initiation of apoptosis , 2000, British Journal of Cancer.

[25]  Carmel Mothersill,et al.  Relative Contribution of Bystander and Targeted Cell Killing to the Low-Dose Region of the Radiation Dose–Response Curve , 2000, Radiation research.

[26]  C. Mothersill,et al.  Involvement of energy metabolism in the production of ‘bystander effects’ by radiation , 2000, British Journal of Cancer.

[27]  K. Trott,et al.  Delayed lethality, apoptosis and micronucleus formation in human fibroblasts irradiated with X-rays or alpha-particles. , 1999, International journal of radiation biology.

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

[29]  C. Mothersill,et al.  Cell-cell contact during gamma irradiation is not required to induce a bystander effect in normal human keratinocytes: evidence for release during irradiation of a signal controlling survival into the medium. , 1998, Radiation research.

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

[31]  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.

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

[33]  A. Giaccia,et al.  Isolation and characterization of glucose-6-phosphate dehydrogenase-deficient Chinese hamster cells derived from pure mutant colonies. , 1989, Mutagenesis.

[34]  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.

[35]  T. Puck,et al.  ACTION OF X-RAYS ON MAMMALIAN CELLS , 1956, The Journal of experimental medicine.