Modulation of Radiation Responses by Pre-exposure to Irradiated Cell Conditioned Medium

Abstract Maguire, P., Mothersill, C., McClean, B., Seymour, C. and Lyng, F. M. Modulation of Radiation Responses by Pre-exposure to Irradiated Cell Conditioned Medium. Radiat. Res. 167, 485–492 (2007). The aim of this study was to investigate whether exposure of HPV-G cells to irradiated cell conditioned medium (ICCM) could induce an adaptive response if the cells were subsequently challenged with a higher ICCM dose. Clonogenic survival and major steps in the cascade leading to apoptosis, such as calcium influx and loss of mitochondrial membrane potential, were examined to determine whether these events could be modified by giving a priming dose of ICCM before the challenge dose. Clonogenic survival data indicated an ICCM-induced adaptive response in HPV-G cells “primed” with 5 mGy or 0.5 Gy ICCM for 24 h and then exposed to 0.5 Gy or 5 Gy ICCM. Reactive oxygen species (ROS) were found to be involved in the bystander-induced cell death. Calcium fluxes varied in magnitude across the exposed cell population, and a significant number of the primed HPV-G cells did not respond to the challenge ICCM dose. No significant loss of mitochondrial membrane potential was observed when HPV-G cells were exposed to 0.5 Gy ICCM for 24 h followed by exposure to 5 Gy ICCM for 6 h. Exposure of HPV-G cells to 5 mGy ICCM for 24 h followed by exposure to 0.5 Gy ICCM for 18 h caused a significant increase in mitochondrial mass and a change in mitochondrial location, events associated with the perpetuation of genomic instability. This study has shown that a priming dose of ICCM has the ability to induce an adaptive response in HPV-G cells subsequently exposed to a challenge dose of ICCM.

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

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

[3]  D. Brenner,et al.  Bystander effect and adaptive response in C3H 10T½ cells , 2004 .

[4]  Daniel J. Gould,et al.  N-acetyl-L-cysteine prevents DNA damage induced by UVA, UVB and visible radiation in human fibroblasts. , 2003, Journal of photochemistry and photobiology. B, Biology.

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

[6]  D. Brenner,et al.  Interaction between Radiation-Induced Adaptive Response and Bystander Mutagenesis in Mammalian Cells , 2003, Radiation research.

[7]  W. Morgan,et al.  Persistent oxidative stress in chromosomally unstable cells. , 2003, Cancer research.

[8]  Carmel Mothersill,et al.  Bystander and Delayed Effects after Fractionated Radiation Exposure , 2002, Radiation research.

[9]  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.

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

[11]  Noelle F. Metting,et al.  Adaptive Response and the Bystander Effect Induced by Radiation in C3H 10T½ Cells in Culture , 2001, Radiation research.

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

[13]  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.

[14]  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.

[15]  D. Boreham,et al.  The adaptive response modifies latency for radiation-induced myeloid leukemia in CBA/H mice. , 1999, Radiation research.

[16]  C. Mothersill,et al.  The effect of microcolony size, at time of irradiation, on colony forming ability. , 1999, International journal of radiation biology.

[17]  J. Little,et al.  Intercellular communication is involved in the bystander regulation of gene expression in human cells exposed to very low fluences of alpha particles. , 1998, Radiation research.

[18]  D. Goodhead,et al.  Chromosomal instability in the descendants of unirradiated surviving cells after alpha-particle irradiation. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[19]  Christopher C. Goodnow,et al.  Differential activation of transcription factors induced by Ca2+ response amplitude and duration , 1997, Nature.

[20]  C. Mothersill,et al.  Survival of human epithelial cells irradiated with cobalt 60 as microcolonies or single cells. , 1997, International journal of radiation biology.

[21]  C. Mothersill,et al.  Delayed expression of lethal mutations and genomic instability in the progeny of human epithelial cells that survived in a bystander-killing environment. , 1997, Radiation oncology investigations.

[22]  C. Mothersill,et al.  Medium from irradiated human epithelial cells but not human fibroblasts reduces the clonogenic survival of unirradiated cells. , 1997, International journal of radiation biology.

[23]  T. Ikushima,et al.  Radioadaptive response: efficient repair of radiation-induced DNA damage in adapted cells. , 1996, Mutation research.

[24]  H. Kleczkowska,et al.  The role of poly(ADP-ribosyl)ation in the adaptive response. , 1996, Mutation research.

[25]  S. Toledo,et al.  Low-dose ionizing radiation decreases the frequency of neoplastic transformation to a level below the spontaneous rate in C3H 10T1/2 cells. , 1996, Radiation research.

[26]  T. McDonnell,et al.  Apoptosis suppression by bcl-2 is correlated with the regulation of nuclear and cytosolic Ca2+. , 1996, Oncogene.

[27]  A. Fattorossi,et al.  Flow cytometric analysis of the early phases of apoptosis by cellular and nuclear techniques. , 1996, Cytometry.

[28]  P. Wang,et al.  Induction of a cytogenetic adaptive response in germ cells of irradiated mice with very low-dose rate of chronic gamma-irradiation and its biological influence on radiation-induced DNA or chromosomal damage and cell killing in their male offspring. , 1995, Mutagenesis.

[29]  M. Sasaki.  On the reaction kinetics of the radioadaptive response in cultured mouse cells. , 1995, International journal of radiation biology.

[30]  E. Azzam,et al.  Radiation-induced adaptive response for protection against micronucleus formation and neoplastic transformation in C3H 10T1/2 mouse embryo cells. , 1994, Radiation research.

[31]  J. Bereiter-Hahn,et al.  Dynamics of mitochondria in living cells: Shape changes, dislocations, fusion, and fission of mitochondria , 1994, Microscopy research and technique.

[32]  Peter Lipp,et al.  Ratiometric confocal Ca2+-measurements with visible wavelength indicators in isolated cardiac myocytes , 1993 .

[33]  John Calvin Reed,et al.  Apoptosis induced by withdrawal of interleukin-3 (IL-3) from an IL-3-dependent hematopoietic cell line is associated with repartitioning of intracellular calcium and is blocked by enforced Bcl-2 oncoprotein production. , 1993, The Journal of biological chemistry.

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

[35]  A. Batova,et al.  Increased sensitivity of human keratinocytes immortalized by human papillomavirus type 16 DNA to growth control by retinoids. , 1992, Cancer research.

[36]  J. D. Young,et al.  Ionophore-induced apoptosis: role of DNA fragmentation and calcium fluxes. , 1991, Experimental cell research.

[37]  T. Ikushima.  Radio-adaptive response: characterization of a cytogenetic repair induced by low-level ionizing radiation in cultured Chinese hamster cells. , 1989, Mutation research.

[38]  S. Wolff,et al.  Characterization of the adaptive response to ionizing radiation induced by low doses of X rays to human lymphocytes. , 1987, Radiation research.

[39]  S. Wolff,et al.  Very low doses of X-rays can cause human lymphocytes to become less susceptible to ionizing radiation. , 1987, Mutagenesis.

[40]  S. Wolff,et al.  Adaptive response of human lymphocytes to low concentrations of radioactive thymidine. , 1984, Science.

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