title: Chronic Low Dose Rate Ionizing Radiation Exposure Induces Premature Senescence in Human Fibroblasts that Correlates with Up Regulation of Proteins Involved in Protection against Oxidative Stress.
abstract: The risks of non-cancerous diseases associated with exposure to low doses of radiation are at present not validated by epidemiological data, and pose a great challenge to the scientific community of radiation protection research. Here, we show that premature senescence is induced in human fibroblasts when exposed to chronic low dose rate (LDR) exposure (5 or 15 mGy/h) of gamma rays from a137Cs source. Using a proteomic approach we determined differentially expressed proteins in cells after chronic LDR radiation compared to control cells. We identified numerous proteins involved in protection against oxidative stress, suggesting that these pathways protect against premature senescence. In order to further study the role of oxidative stress for radiation induced premature senescence, we also used human fibroblasts, isolated from a patient with a congenital deficiency in glutathione synthetase (GS). We found that these GS deficient cells entered premature senescence after a significantly shorter time of chronic LDR exposure as compared to the GS proficient cells. In conclusion, we show that chronic LDR exposure induces premature senescence in human fibroblasts, and propose that a stress induced increase in reactive oxygen species (ROS) is mechanistically involved.
authors.affiliation: Division of Translational Medicine and Chemical Biology, Science for Life Laboratory, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm S-171 21, Sweden. olga.loseva@scilifelab.se.
authors.forename: Olga
authors.initials: O
authors.lastname: Loseva
authors.affiliation: Sahlgrenska Cancer Center, Department of Clinical Genetics, Institute of Biomedicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg SE-41345, Sweden. emman.shubbar@gu.se.
authors.forename: Emman
authors.initials: E
authors.lastname: Shubbar
authors.affiliation: Center for Radiation Protections Research, Department of Molecular Biosciences, The Wenner Gren Institute, Stockholm University, Stockholm S-106 91, Sweden. siamak.haghdoost@su.se.
authors.forename: Siamak
authors.initials: S
authors.lastname: Haghdoost
authors.affiliation: Division of Molecular Carcinogenesis, The Netherlands Cancer Institute, Amsterdam 1066 CX, Netherlands. b.evers@nki.nl.
authors.forename: Bastiaan
authors.initials: B
authors.lastname: Evers
authors.affiliation: Division of Translational Medicine and Chemical Biology, Science for Life Laboratory, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm S-171 21, Sweden. thomas.helleday@scilifelab.se.
authors.forename: Thomas
authors.initials: T
authors.lastname: Helleday
authors.affiliation: Center for Radiation Protections Research, Department of Molecular Biosciences, The Wenner Gren Institute, Stockholm University, Stockholm S-106 91, Sweden. mats.harms-ringdahl@su.se.
authors.forename: Mats
authors.initials: M
authors.lastname: Harms-Ringdahl
keywords: human fibroblasts; ionizing radiation; low dose chronic exposure; premature senescence; proteomics