DNA damaging bystander signalling from stem cells,cancer cells and fibroblasts after Cr(VI) exposure and its dependence on telomerase |
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Authors: | Nicola Cogan Duncan M Baird Ryan Phillips Lucy A Crompton Maeve A Caldwell Miguel A Rubio Roger Newson Fiona Lyng C Patrick Case |
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Institution: | 1. Bristol Implant Research Centre, University of Bristol, Bristol, BS10 5NB, UK;2. Department of Pathology School of Medicine, Cardiff University, Henry Wellcome Building for Biomedical Research in Wales, Heath Park, Cardiff, CF14 4XN, UK;3. Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, University of Bristol, Bristol, BS1 3NY, UK;4. Center of Regenerative Medicine in Barcelona, CMRB Dr. Aiguader, 88, 7th Floor, 08003 Barcelona, Spain;5. Radiation and Environmental Science Centre, Focas Institute, Dublin Institute of Technology, Dublin 2, Ireland;6. National Heart and Lung Institute, Imperial College London, London, SW7 2AZ, UK |
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Abstract: | The bystander effect is a feature of low dose radiation exposure and is characterized by a signaling process from irradiated cells to non irradiated cells, which causes DNA and chromosome damage in these ‘nearest neighbour’ cells. Here we show that a low and short dose of Cr(VI) can induce stem cells, cancer cells and fibroblasts to chronically secrete bystander signals, which cause DNA damage in neighboring cells. The Cr(VI) induced bystander signaling depended on the telomerase status of either cell. Telomerase negative fibroblasts were able to receive DNA damaging signals from telomerase positive or negative fibroblasts or telomerase positive cancer cells. However telomerase positive fibroblasts were resistant to signals from Cr(VI) exposed telomerase positive fibroblasts or cancer cells. Human embryonic stem cells, with positive Oct4 staining as a marker of pluripotency, showed no significant increase of DNA damage from adjacent Cr and mitomycin C exposed fibroblasts whilst those cells that were negatively stained did. This selectivity of DNA damaging bystander signaling could be an important consideration in developing therapies against cancer and in the safety and effectiveness of tissue engineering and transplantation using stem cells. |
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