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- 2. The bystander effect refers to the induction of biological effects in cells that are not directly
- 3. Non-targeted biological effects of ionizing radiation
- 5. Non-targeted effects of ionizing radiation as a new paradigm of radiation biology Ward, J. (1999) New
- 12. Bystander effect and genomic instability
- 73. Experiments suggest that the effect is due to a molecule secreted by irradiated cells, which is
- 74. The radiation-induced bystander effect is defined as “the induction of biological effects in cells that are
- 75. GENERATIONS OF students in radiation biology have been taught that heritable biological effects require direct damage
- 76. In the radiation field, it has come to be loosely defined as the induction of biological
- 77. The plethora of data now available concerning the bystander effect fall into two quite separate categories,
- 78. Medium transfer experiments Experiments involving the transfer of medium from irradiated to unirradiated cells have demonstrated
- 79. This bystander effect suggested that irradiated cells secreted a molecule into the culture medium that was
- 80. Some limited progress has been made in the search for the mechanisms involved in this bystander
- 81. The majority of bystander experiments involving medium transfer have utilized low-LET x or gamma rays, in
- 82. Micronuclei in normal human fibroblasts Perhaps the most direct and most dramatic demonstration of the bystander
- 83. Fig. 1. The bystander effect with human fibroblasts. Cells of one population were stained with the
- 84. Cell lethality Lines of hygromycin- and neomycin-resistant V79 cells were produced. Before exposure the hygromycinresistant cells
- 85. Fig. 2. The bystander effect for cell survival in V79 cells. Each data point (mean ±
- 86. There is a considerable degree of cell killing in the nonhit cells, implying a substantial bystander
- 87. Mutagenic effects in human-hamster hybrid cells Zhou et al. (2000) reported a study in which human-hamster
- 88. These mutations must clearly arise from neighbor cells, not directly exposed, but in close proximity to
- 89. Oncogenic transformation in mouse fibroblasts Mouse fibroblast (C3H10T1⁄2) cells were plated in a monolayer, and the
- 90. It is important to note that the experimental results discussed in this paper involve laboratory model
- 91. This is illustrated in Fig. 6 which combines the data of Zhou et al. (2001), in
- 92. Under these experimental conditions, it is evident that a linear extrapolation of risks from high doses
- 93. Ionizing radiation Radiated cell BE factor migration (signal) Effects in non - radiated cells BYSTANDER EFFECT
- 94. Scheme of BE induced in vivo (MN test) 6000 cells seeded in 24 cm2 flasks Blood
- 96. Killing Non-transduced Tumor Cells via Bystander Effect The bystander effect was first reported by Moolten (1986)
- 97. Schematic overview of the Bystander effect
- 98. Our understanding of how radiation kills normal and tumour cells has been based on an intimate
- 99. When ionizing radiation interacts with biological material, energy is deposited and chemical bonds are broken. In
- 100. Direct DNA damage radiation model. The schematic shows the standard model of DNA damage responses to
- 101. The mechanisms underpinning DNA damage and repair processing in irradiated cells have been extensively studied since
- 102. Evidence now shows that, as well as these direct DNA damage-dependent effects, irradiated cells also send
- 103. For example, the archetypal gene therapy model is the herpes simplex virus-thymidine kinase (HSV-TK) system. In
- 104. Radiation-induced bystander responses have been observed in a range of cell types, tissue models and in
- 105. Targeted Effects of Ionizing Radiation Cell Damage Induction of death repaired clonal genetic alteration
- 106. Untargeted Effects of Exposure to Ionizing Radiation Effects in unexposed cells and their progeny i.e. in
- 107. Radiation-induced Genomic Instability micronucleus chromosome aberration cell death gene mutation mitotic failure aneuploidy
- 108. Radiation-induced Genomic Instability A genome-wide process induced at very high frequency High LET tends to be
- 109. Bystander Effects of Ionizing Radiation Signals via gap junctions Signals via medium/plasma N.B. 1950s and 60s
- 110. Bystander Effects of Ionizing Radiation Increases in damage-inducible proteins Decreases in damage-inducible proteins Increases in reactive
- 111. Bystander Effects of Ionizing Radiation Target for biological effects is larger than the cell Important implications
- 112. The Linear No Threshold Problem Induced Effect Dose Threshold supralinear Supralinear linear Threshold sublinear Hormesis Non-targeted
- 113. DNA Damage Genome stability
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