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Chronic irradiation of human cells reduces histone levels and deregulates gene expression

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Lowe, Donna J. 
Herzog, Mareike 
Mosler, Thorsten 
Cohen, Howard 


Abstract: Over the past decades, there have been huge advances in understanding cellular responses to ionising radiation (IR) and DNA damage. These studies, however, were mostly executed with cell lines and mice using single or multiple acute doses of radiation. Hence, relatively little is known about how continuous exposure to low dose ionising radiation affects normal cells and organisms, even though our cells are constantly exposed to low levels of radiation. We addressed this issue by examining the consequences of exposing human primary cells to continuous ionising γ-radiation delivered at 6–20 mGy/h. Although these dose rates are estimated to inflict fewer than a single DNA double-strand break (DSB) per hour per cell, they still caused dose-dependent reductions in cell proliferation and increased cellular senescence. We concomitantly observed histone protein levels to reduce by up to 40%, which in contrast to previous observations, was not mainly due to protein degradation but instead correlated with reduced histone gene expression. Histone reductions were accompanied by enlarged nuclear size paralleled by an increase in global transcription, including that of pro-inflammatory genes. Thus, chronic irradiation, even at low dose-rates, can induce cell senescence and alter gene expression via a hitherto uncharacterised epigenetic route. These features of chronic radiation represent a new aspect of radiation biology.



Article, /631/45/147, /631/80/509, /631/208/176, /631/337/100, /631/337/2019, /13/106, /38/77, /38/91, /82/1, /82/58, /96/63, article

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Scientific Reports

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Nature Publishing Group UK
Cancer Research UK (CRUK) (C6/A18796, C6/A18796 and C6946/A24843, C6/A18796 and C6946/A24843)
Wellcome Trust (Wellcome) (206388/Z/17/Z, 206388/Z/17/Z and WT203144, 206388/Z/17/Z and WT203144)
Deutsche Forschungsgemeinschaft (German Research Foundation) (393547839 – SFB 1361, 393547839 – SFB 1361)