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Aim: To studythe characterization and radiation protection effect of Sipunculus nudusL.polysaccharide (SNP).Methods: SNP was prepared from Sipunculus nudusL.by the processes of NaOH extraction, trichloroacetic acid deprotein, alcohol precipitation, DEAE-Cellulose 52 ion exchange chromatography and SephcrylTM S-300 sieve chromatography.The structural feature of SNP was investigated by monosaccharide analysis, high performance gel permeation chromatography (HPGPC),Fourier transform-infrared (FT-IR) spectroscopy, and nuclear magnetic resonance (NMR) spectroscopy.The radiation protection effect of SNP was studied on the irradiated mice.30-day survival rate, RBC, WBC and HGB counts in peripheral blood, the index of superoxide dismulases (SOD) activities,malondialdehyde (MDA) levels, Glutathione peroxidase (GSH-PX) levels in blood serum and the content of deoxyribonucleic acid (DNA) in bone marrow were measured.Results: SNP was composed of glucoseand galacturonic acid and the relatively molar percentage were 88.8% and 7.5% respectively.The molecular weight was 473kDa.The mice in SNP group (90 mg/kg) and SNP group (270 mg/kg) survived significantly longer than those in irradiated control group, the 30-day survival rate reached 20%.Compared with radiation-treated group, experimental groups of SNP showed significant protecting effect on radiation induced oxidative damages.The results of Peripheral blood counts suggest that SNP could reduce the effects of radiation on hemograms in irradiated mice.The contents of DNA in bone marrow were significantly increased by SNP treatment in a dose-dependent manner.Conclusion These findings suggest that SNP possesses marked antioxidant and hematopoiesis capacity which play important roles in the prevention of radiation damage in mice induced by 137Cs gamma-irradiation.