Radiation-Induced Bystander Effects

Background: The bystander effect is a relatively new area of radiobiological research, which is aimed at studying post-radiation changes in neighboring non-hit cells or tissues. The bystander effect of ionizing irradiation is important after low-dose irradiation in the range of up to 0.2 Gy, where a higher incidence of stochastic damage was observed than was expected from a linear-quadratic model. It is also important when the irradiation of a cell population is highly non-uniform. Objective: This review summarizes most of the important results and proposed bystander effect mechanisms as well as their impact on theory and clinical practice. The literature, in parts contradictory, is collected, the main topics are outlined, and some basic papers are described in more detail. In order to illustrate the microbeam technique, which is considered relevant for the bystander effect research, the state of the Leipzig LIPSION nanoprobe facility is described. Results: The resistence of a radiation-induced bystander effect is now generally accepted. The current state of knowledge on it is summarized here. Several groups worldwide are working on understanding its different aspects and its impact on radiobiology and radiation protection. Conclusion: The observation of a bystander effect has posed many questions, and answering them is a challenging topic for radiobiology in the future.Hintergrund: Der strahleninduzierte Bystander-Effekt ist ein relativ neues Feld der strahlenbiologischen Forschung. Im Zentrum steht die Reaktion nicht direkt selbst getroffener Zellen oder Gewebe auf ionisierende Strahlung. Der strahleninduzierte Bystander-Effekt spielt eine wichtige Rolle vor allem im Niedrigdosisbereich ≤ 0,2 Gy, wo die Inzidenz des stochastischen Zellschadens in Experimenten größer ist als die Berechnung nach dem linearquadratischen Modell. Eine weitere wichtige Rolle spielt der Bystander-Effekt, wenn die Bestrahlung einer Zellpopulation hochgradig nichtuniform ist. Ziel: Dieser Übersichtsartikel fasst die wichtigsten Ergebnisse der Bystander-Effekt-Forschung zusammen und gibt einen Ausblick auf mögliche Mechanismen sowie auf die Bedeutung für Theorie und klinische Praxis. Die teilweise widersprüchliche Literatur zum Bystander-Effekt wird zusammengefasst und nach den Hauptthemen unterteilt, und einige grundlegende Artikel werden ausführlicher dargestellt. Zur Veranschaulichung der für den Bystander-Effekt relevanten Mikrobeam-Technik stellen wir den aktuellen Stand an der Leipziger Nanosonde LIPSION vor. Ergebnisse: Die Existenz eines radiogenen Bystander-Effekts ist inzwischen allgemein anerkannt. Der Stand des Wissens wird hier zusammengefasst. Weltweit befassen sich mehrere Arbeitsgruppen mit der Vertiefung der Erkenntnisse seiner verschiedenen Aspekte und den Folgen für Radiobiologie und Radioprotektion. Schlussfolgerung: Der Bystander-Effekt hat viele Fragen aufgeworfen, deren Beantwortung eine Herausforderung der Radiobiologie der Zukunft ist.

[1]  W. Anderson,et al.  Intercellular communication mediates the bystander effect during herpes simplex thymidine kinase/ganciclovir-based gene therapy of human gastrointestinal tumor cells. , 1998, Human gene therapy.

[2]  J. Trosko,et al.  Cell-cell communication in carcinogenesis. , 1998, Frontiers in bioscience : a journal and virtual library.

[3]  B. Marples,et al.  The response of Chinese hamster V79 cells to low radiation doses: evidence of enhanced sensitivity of the whole cell population. , 1993, Radiation research.

[4]  S. Breit,et al.  Radiation and the lung: a reevaluation of the mechanisms mediating pulmonary injury. , 1995, International journal of radiation oncology, biology, physics.

[5]  L. Braby,et al.  Cellular effects of individual high-linear energy transfer particles and implications for tissue response at low doses. , 1997, Radiation research.

[6]  G. Stein.  The molecular basis of cell cycle and growth control , 1999 .

[7]  P. Lindop.  Biological Effects of Radiation , 1957, Nature.

[8]  J. Van Dyk,et al.  Partial volume rat lung irradiation: an evaluation of early DNA damage. , 1998, International journal of radiation oncology, biology, physics.

[9]  R Roots,et al.  Estimation of life times and diffusion distances of radicals involved in x-ray-induced DNA strand breaks of killing of mammalian cells. , 1975, Radiation research.

[10]  S. Tannenbaum,et al.  DNA damage and mutation in human cells exposed to nitric oxide in vitro. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[11]  J. Trosko,et al.  Cytotoxic, mutagenic, and cell-cell communication inhibitory properties of DDT, lindane, and chlordane on Chinese hamster cellsin vitro , 1983, Archives of environmental contamination and toxicology.

[12]  K M Prise,et al.  Direct evidence for a bystander effect of ionizing radiation in primary human fibroblasts , 2001, British Journal of Cancer.

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

[14]  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.

[15]  G Schettino,et al.  A charged-particle microbeam: I. Development of an experimental system for targeting cells individually with counted particles. , 1997, International journal of radiation biology.

[16]  C. Streffer,et al.  p53 Levels, Cell Cycle Kinetics and Radiosensitivity in Two SV40 Transformed Wi38VA13 Fibroblast Strains , 2001, Strahlentherapie und Onkologie.

[17]  I. Emerit.  Reactive oxygen species, chromosome mutation, and cancer: possible role of clastogenic factors in carcinogenesis. , 1994, Free radical biology & medicine.

[18]  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.

[19]  Seaver,et al.  Nitric oxide as a secretory product of mammalian cells , 2004 .

[20]  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.

[21]  K. Suzuki,et al.  Radioprotective effects of dimethyl sulfoxide in golden hamster embryo cells exposed to gamma rays at 77 K. II. Protection from lethal, chromosomal, and DNA damage. , 1990, Radiation research.

[22]  C. Harris,et al.  Nitric oxide-induced p53 accumulation and regulation of inducible nitric oxide synthase expression by wild-type p53. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[23]  E. Frome,et al.  Modulation of radiation-induced chromosome aberrations by DMSO, an OH radical scavenger. 1: Dose-response studies in human lymphocytes exposed to 220 kV X-rays. , 1988, International journal of radiation biology and related studies in physics, chemistry, and medicine.

[24]  David N. Jamieson,et al.  The Leipzig high-energy ion nanoprobe: A report on first results , 2000 .

[25]  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.

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

[27]  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.

[28]  David J. Brenner,et al.  The Columbia University Single-Ion Microbeam , 2001, Radiation research.

[29]  E. Feinstein,et al.  Stress-induced secretion of growth inhibitors: a novel tumor suppressor function of p53 , 1998, Oncogene.

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

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

[32]  H. Sakurai,et al.  p53 mutation decreased radiosensitivity in rat yolk sac tumor cell lines. , 1999, International journal of radiation oncology, biology, physics.

[33]  K. Prise,et al.  Single ion actions: the induction of micronuclei in V79 cells exposed to individual protons. , 2000, Advances in space research : the official journal of the Committee on Space Research.

[34]  K. Held,et al.  Role of the pentose cycle in oxygen radical-mediated toxicity of the thiol-containing radioprotector dithiothreitol in mammalian cells. , 1993, Radiation research.

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

[36]  D. Brenner,et al.  The Bystander Effect in Radiation Oncogenesis: I. Transformation in C3H 10T½ Cells In Vitro can be Initiated in the Unirradiated Neighbors of Irradiated Cells , 2001, Radiation research.

[37]  J. Battista,et al.  In-field and out-of-field effects in partial volume lung irradiation in rodents: possible correlation between early dna damage and functional endpoints. , 2000, International journal of radiation oncology, biology, physics.

[38]  T. Ohnishi,et al.  Binding between wild-type p53 and hsp72 accumulated after UV and gamma-ray irradiation. , 1995, Cancer letters.

[39]  D. J. Brenner,et al.  The Bystander Effect in Radiation Oncogenesis: II. A Quantitative Model , 2001, Radiation research.

[40]  A. Nias.  Radiation Biology in Cancer Research , 1980, British Journal of Cancer.

[41]  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.

[42]  J. Hendry,et al.  Radiobiology for the Radiologist , 1979, British Journal of Cancer.

[43]  J. Trosko,et al.  Modulation of intercellular communication during radiation and chemical carcinogenesis. , 1990, Radiation research.

[44]  G. Schettino,et al.  A Focused Ultrasoft X-Ray Microbeam for Targeting Cells Individually with Submicrometer Accuracy , 2001, Radiation research.

[45]  G. Hildebrandt,et al.  Funktionelle und molekulare Aspekte der antiinflammatorischen Wirkung niedrig dosierter Radiotherapie , 2002, Strahlentherapie und Onkologie.

[46]  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.

[47]  C. Geard,et al.  Targeted cytoplasmic irradiation with alpha particles induces mutations in mammalian cells. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

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

[49]  E. Hall,et al.  Induction of a bystander mutagenic effect of alpha particles in mammalian cells. , 2000, Proceedings of the National Academy of Sciences of the United States of America.