A systems radiation biology approach to unravel the role of chronic low-dose-rate gamma-irradiation in inducing premature senescence in endothelial cells

Gabriel Babini, Giorgio Baiocco, Sofia Barbieri, Jacopo Morini, Traimate Sangsuwan, Siamak Haghdoost, Ramesh Yentrapalli, Omid Azimzadeh, Charlotte Rombouts, An Aerts, Roel Quintens, Teni Ebrahimian, Rafi Benotmane, Raghda Ramadan, Sarah Baatout, Soile Tapio, Mats Harms-Ringhdahl, Andrea Ottolenghi

    Research outputpeer-review


    Purpose: The aim of this study was to explore the effects of chronic low-dose-rate gamma-radiation at a multi-scale level. The specific objective was to obtain an overall view of the endothelial cell response, by integrating previously published data on different cellular endpoints and highlighting possible different mechanisms underpinning radiation-induced senescence.
    Materials and methods: Different datasets were collected regarding experiments on human umbilical vein endothelial cells (HUVECs) which were chronically exposed to low dose rates (0, 1.4, 2.1 and 4.1 mGy/h) of gamma-rays until cell replication was arrested. Such exposed cells were analyzed for different complementary endpoints at distinct time points (up to several weeks), investigating cellular functions such as proliferation, senescence and angiogenic properties, as well as using transcriptomics and proteomics profiling. A mathematical model was proposed to describe proliferation and senescence.
    Results: Simultaneous ceasing of cell proliferation and senescence onset as a function of time were well reproduced by the logistic growth curve, conveying shared equilibria between the two endpoints. The combination of all the different endpoints investigated highlighted a dose-dependence for prematurely induced senescence. However, the underpinning molecular mechanisms appeared to be dissimilar for the different dose rates, thus suggesting a more complex scenario.
    Conclusions: This study was conducted integrating different datasets, focusing on their temporal dynamics, and using a systems biology approach. Results of our analysis highlight that different dose rates have different effects in inducing premature senescence, and that the total cumulative absorbed dose also plays an important role in accelerating endothelial cell senescence.
    Original languageEnglish
    Article numbere0265281
    Number of pages17
    JournalPLOS ONE
    Issue number3
    StatePublished - 14 Mar 2022

    Cite this