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In recent years there has been a paradigm shift in radiobiology, to one which induces non-targeted effects, such as the bystander effect and genomic instability. The bystander effect has been defined as effects seen in cells that although never exposed to radiation, display similar effects to those that have, due to some form of communication with directly hit cells. This investigation aims to further the current understanding of this effect using three different models, cell lines, primary explant cultures and whole animals. Multiple cell lines were used to determine the relative importance of bystander signal production versus the response in the exposed cell line. In the case of responding cell lines, the signal generated from the cells exposed to direct radiation determined the magnitude of the response in the bystander cell. A primary tissue culture model, in conjunction with a cell line reporter system was used to investigate the bystander effect generated by epithelial tissue in-vitro. Apoptosis related protein expression was determined over a range of doses for both direct radiation and bystander signal exposure. The signal generated from tissue cultured in-vitro induced protein expression changes in the exposed issue and a reduction in cell survival. To further examine signal production in tissue, mice on an antioxidant diet were used for both in-vitro and in-vivo exposures using the tissue culture/reporter cell line system to measure effects. While there were significant differences between normal and anti-oxidant mice, the most interesting results of this study was in the differences between in-vitro and in-vivo exposure, and the male and female mice. These results indicated that while much valuable information about the bystander effect may be gained from various types of in-vitro models, it is important that more in-vivo models are developed, while they are ultimately more complex, they are also a more accurate reflection of the true nature of this phenomenon.
Vines, Alice. An examination of the bystander effect in multiple models: from cell line to in-vivo exposure. Dublin : Dublin Institute of Technology, 2007