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Mothersill C.,McMaster University | Antonelli F.,Ionising Radiation Biophysics and Biomedical Physics Unit | Dahle J.,Institute for Cancer Research | Dini V.,Ionising Radiation Biophysics and Biomedical Physics Unit | And 12 more authors.
International Journal of Radiation Biology | Year: 2012

Purpose: Recent research has suggested that serotonin may play an important role in the expression of radiation-induced bystander effects. Serotonin levels in serum were reported to range from 622 μM and to correlate inversely with the magnitude of cellular colony-forming ability in medium transfer bystander assays. That is, high serotonin concentration correlated with a low cloning efficiency in cultures receiving medium derived from irradiated cells. Methods: Because of the potential importance of this observation, the European Union's Non-targeted Effects Integrated Project (NOTE) performed an inter-comparison exercise where serum samples with high and low serotonin levels were distributed to seven laboratories which then performed their own assay to determine the magnitude of the bystander effect. Results: The results provided some support for a role for serotonin in four of the laboratories. Two saw no difference between the samples and one gave inconclusive results. In this summary paper, full data sets are presented from laboratories whose data was inconclusive or insufficient for a full paper. Other data are published in full in the special issue. Conclusion: The data suggest that there may be multiple bystander effects and that the underlying mechanisms may be modulated by both the culture conditions and the intrinsic properties of the cells used in the assay. © 2012 Informa UK, Ltd. Source

Sandor N.,F Joliot Curie National Research Institute For Radiobiology And Radiohygiene | Schilling-Toth B.,F Joliot Curie National Research Institute For Radiobiology And Radiohygiene | Kis E.,F Joliot Curie National Research Institute For Radiobiology And Radiohygiene | Benedek A.,F Joliot Curie National Research Institute For Radiobiology And Radiohygiene | And 4 more authors.
Mutation Research - Genetic Toxicology and Environmental Mutagenesis | Year: 2015

We have investigated the importance of GDF-15 (secreted cytokine belonging to the TGF-β superfamily) in low and high dose radiation-induced cellular responses. A telomerase immortalized human fibroblast cell line (F11hT) was used in the experiments. A lentiviral system encoding small hairpin RNAs (shRNA) was used to establish GDF-15 silenced cells. Secreted GDF-15 levels were measured in culture medium by ELISA. Cell cycle analysis was performed by flow cytometry. The experiments demonstrated that in irradiated human fibroblasts GDF-15 expression increased with dose starting from 100. mGy. Elevated GDF-15 expression was not detected in bystander cells. The potential role of GDF-15 in radiation response was investigated by silencing GDF-15 in immortalized human fibroblasts with five different shRNA encoded in lentiviral vectors. Cell lines with considerably reduced GDF-15 levels presented increased radiation sensitivity, while a cell line with elevated GDF-15 was more radiation resistant than wild type cells. We have investigated how the reduced GDF-15 levels alter the response of several known radiation inducible genes. In F11hT-shGDF-15 cells the basal expression level of CDKN1A was unaltered relative to F11hT cells, while GADD45A and TGF-β1 mRNA levels were slightly higher, and TP53INP1 was considerably reduced. The radiation-induced expression of TP53INP1 was lower in the silenced than in wild type fibroblast cells. Cell cycle analysis indicated that radiation-induced early G2/M arrest was abrogated in GDF-15 silenced cells. Moreover, radiation-induced bystander effect was less pronounced in GDF-15 silenced fibroblasts. In conclusion, the results suggest that GDF-15 works as a radiation inducible radiation resistance increasing factor in normal human fibroblast cells, acts by regulating the radiation-induced transcription of several genes and might serve as a radiation-induced early biomarker in exposed cells. © 2015 Elsevier B.V. Source

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