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  • 标题:Genistein Protects Against Biomarkers of Delayed Lung Sequelae in Mice Surviving High-Dose Total Body Irradiation
  • 其他标题:Genistein Protects Against Biomarkers of Delayed Lung Sequelae in Mice Surviving High-Dose Total Body Irradiation
  • 本地全文:下载
  • 作者:Regina M. DAY ; Michal BARSHISHAT-KUPPER ; Steven R. MOG
  • 期刊名称:Journal of Radiation Research
  • 印刷版ISSN:0449-3060
  • 电子版ISSN:1349-9157
  • 出版年度:2008
  • 卷号:49
  • 期号:4
  • 页码:361-372
  • DOI:10.1269/jrr.07121
  • 摘要:The effects of genistein on 30-day survival and delayed lung injury were examined in C57BL/6J female mice. A single subcutaneous injection of vehicle (PEG-400) or genistein (200 mg/kg) was administered 24 h before total body irradiation (7.75 Gy 60 Co, 0.6 Gy/min). Experimental groups were: No treatment Sham (NC), Vehicle Sham (VC), Genistein Sham (GC), Radiation only (NR), Vehicle Radiation (VR), Genistein Radiation (GR). Thirty-day survivals after 7.75 Gy were: NR 23%, VR 53%, and GR 92%, indicating significant protection from acute radiation injury by genistein. Genistein also mitigated radiation-induced weight loss on days 13-28 postirradiation. First generation lung fibroblasts were analyzed for micronuclei 24 h postirradiation. Fibroblasts from the lungs of GR-treated mice had significantly reduced micronuclei compared with NR mice. Collagen deposition was examined by histochemical staining. At 90 days postirradiation one half of the untreated and vehicle irradiated mice had focal distributions of small collagen-rich plaques in the lungs, whereas all of the genistein-treated animals had morphologically normal lungs. Radiation reduced the expression of COX-2, transforming growth factor-β receptor (TGFβR) I and II at 90 days after irradiation. Genistein prevented the reduction in TGFβRI. However, by 180 days postirradiation, these proteins normalized in all groups. These results demonstrate that genistein protects against acute radiation-induced mortality in female mice and that GR-treated mice have reduced lung damage compared to NR or VR. These data suggest that genistein is protective against a range of radiation injuries.
  • 关键词:Total body irradiation; Lung fibrosis; Genistein; Radioprotection; Micronuclei; Pneumonitis
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