Authors: Juliann G Kiang Bradley R Garrison Joan T Smith Risaku Fukumoto
Publish Date: 2014/05/07
Volume: 393, Issue: 1-2, Pages: 133-143
Abstract
Ionizing radiation increases cell mortality in a dosedependent manner Increases in DNA double strand breaks γH2AX p53 phophorylation and protein levels of p53 and Bax also occur We investigated the ability of ciprofloxacin CIP a widely prescribed antibiotic to inhibit DNA damage induced by ionizing radiation Human tumor TK6 NH32 p53 −/− of TK6 cells and human normal peripheral blood mononuclear cells PBMCs were exposed to 2–8 Gy 60Coγphoton radiation γH2AX an indicator of DNA strand breaks phosphorylated p53 responsible for cellcycle arrest Bcl2 an apoptotic protein and cell death were measured Ionizing irradiation increased γH2AX amounts in TK6 cells p53+/+ within 1 h in a radiation dosedependent manner CIP pretreatment and posttreatment effectively inhibited the increase in γH2AX CIP pretreatment reduced Bcl2 production but promoted p53 phosphorylation caspase3 activation and cell death In NH32 cells CIP failed to significantly inhibit the radiationinduced γH2AX increase suggesting that CIP inhibition involves in p53dependent mechanisms In normal healthy human PBMCs CIP failed to block the radiationinduced γH2AX increase but effectively increased Bcl2 production but blocked the phosphop53 increase and subsequent cell death CIP increased Gadd45α and enhanced p21 protein 24 h postirradiation Results suggest that CIP exerts its effect in TK6 cells by promoting p53 phosphorylation and inhibiting Bcl2 production and in PBMCs by inhibiting p53 phosphorylation and increasing Bcl2 production Our data are the first to support the view that CIP may be effective to protect normal tissue cells from radiation injury while enhancing cancer cell death in radiation therapyWe thank Dr Vitaly Nagy and the radiation source staff for radiation dosimetry and source operation Ms Lisa FT Meyers Dr Dennis P McDaniel in the Biomedical Instrumentation Center at USUHS Dr Minnie Malik in the Department of Obstetrics and Gynecology at USUHS HM1 Marsha Anderson USN and Mr True M Burns at AFRRI for their technical support
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