紫薯素对~(60)Coγ辐射导致的小鼠胸腺细胞损伤的抑制作用及机制
|
摘要
目的建立~(60)Coγ辐射对体外培养的小鼠胸腺细胞损伤的病理模型,探讨在~(60)Co辐射下,紫薯素抑制~(60)Co诱导的小鼠胸腺细胞辐射损伤的作用机制。
方法建立紫薯素干预~(60)Coγ辐射小鼠胸腺细胞的模型。应用MTT,首先检测~(60)Coγ辐射在0～12h范围内对小鼠胸腺细胞活力的影响,~(60)Co分为0,2,4,6Gy四个不同剂量进行单次辐射。不同剂量的紫薯素预处理细胞,MTT检测紫薯素对辐射细胞活力的影响、抗辐射的有效剂量以及其有无毒性反应。紫薯素对辐射细胞的作用检测中,通过DNA ladder检测细胞晚期凋亡;以流式细胞仪Annexin V-FITC/PI染色检测细胞早期凋亡;流式细胞仪PI染色检测细胞周期。
探讨紫薯素辐射防护作用的机制。测定紫薯素对氧化应激的影响:2,7-二氯氢化荧光素二酯(DCFH-DA)为荧光探针,检测紫薯素对~(60)Co照射后细胞内活性氧(ROS)的影响;酶生化法测定抗氧化酶过氧化物歧化酶(SOD)和谷胱甘肽过氧物酶(GSH-px)的活力。研究紫薯素对~(60)Co诱导小鼠胸腺细胞凋亡的线粒体通路的影响:JC-1荧光染色测定线粒体膜电位;western-blot检测细胞色素C、caspase3和PARP的蛋白表达以及Bcl-2和Bax的蛋白表达;对caspase 3和caspase 9进行酶活性检测。研究紫薯素对~(60)Co诱导小鼠胸腺细胞凋亡的死亡受体通路的影响:RT-PCR检测Fas mRNA;western-blot测定FADD的蛋白表达;caspase8酶活性的检测。检测紫薯素对~(60)Co诱导小鼠胸腺细胞的MAPK途径的影响:western-blot测定磷酸化的ERK、JNK、p38MAPK的蛋白表达。探讨紫薯素对~(60)Co诱导小鼠胸腺细胞p53的影响:RT-PCR检测p53 mRNA;Western-blot检测p53、p21Cip1和p27Kip1的蛋白表达。
结果MTT结果显示: ~(60)Coγ辐射作用于细胞,降低了细胞活力;辐射各组细胞活力从4h开始急剧衰减。4Gy辐射后4h的细胞活力接近50%。本研究选择了4Gy辐射后4h建立细胞损伤模型。辐射后,在0.625g/L～2.500g/L浓度范围内,紫薯素能够提升辐射小鼠胸腺细胞的活力,其提升细胞活力的能力与剂量呈量效依赖关系,而且在此剂量范围内,紫薯素对细胞无毒性。DNA ladder显示:辐射后小鼠胸腺细胞产生明显的ladder,紫薯素干预使DNA ladder减弱。流式检测显示:紫薯素降低了辐射导致的小鼠胸腺细胞早期凋亡,同时缓解了辐射导致的G2/M期细胞周期阻滞。
紫薯素的防辐射机制试验结果显示:紫薯素降低了细胞内ROS的含量,提高了抗氧化酶SOD与GSH-px的活性;稳定了线粒体膜电位,减少细胞色素C的释放,降低caspase 3和PARP的蛋白表达,抑制caspase 9和caspase 3的酶活性,并使Bcl-2蛋白表达升高而Bax蛋白表达降低;对Fas mRNA和FADD蛋白表达无显著作用,但中、高剂量的紫薯素对caspase 8的酶活性有一定的提升;MAPK通路中,紫薯素对ERK活性的影响不明显,对磷酸化的JNK和p38MAPK表达有显著的抑制作用;紫薯素提高p53 mRNA与p53的蛋白表达,抑制p27Kip1的蛋白表达,对p21Cip1蛋白表达的作用不明显。
结论:紫薯素能够有效地抑制~(60)Co辐射引起的小鼠胸腺细胞损伤,提高细胞活力,抑制细胞凋亡,缓解细胞周期阻滞。紫薯素的辐射防护机制包括:抑制了由~(60)Co辐射诱导的细胞氧化损伤,降低ROS,提高抗氧化酶的活性,通过改善氧化还原状态抑制辐射诱导的凋亡;抑制线粒体凋亡信号通路,同时调节Bcl-2、Bax蛋白达到抑制凋亡的目的;对死亡受体凋亡信号通路无作用;MAPK途径中,抑制了JNK与p38MAPK磷酸化,对ERK活性没有影响;通过抑制p53的转录激活和蛋白表达,抑制辐射导致的细胞凋亡;通过抑制p53以及其下游的p27Kip1,缓解细胞周期阻滞。紫薯素通过调节多种基因与蛋白的表达,达到其抗氧化、抗凋亡、缓解细胞周期阻滞的辐射防护作用,有望成为应用广泛的~(60)Co辐射防护剂。
Objective: Establish the ~(60)Coγray-induced irradiation damage model in murine thymocytes. Investigate the protective effects of purple sweet potato(PSP)pigments on ~(60)Co-induced damage.
Methods: After ~(60)Coγray-single dose-irradiation with various doses of 0, 2, 4, 6Gy, the murine thymocytes viabilities are detected by MTT at the post-irradiated time point ranged from 0 to 12h. Treated the thymocytes with indicated dose of irradiation in the present of different concentrations of PSP pigments, the cell viabilities are detected by MTT to investigate the effective and safe concentrations of PSP pigments against irradiation. After the model of PSP pigments against irradiaion is established, DNA ladder is preformed to test whether PSP pigments have the protective effect on late apoptosis. The early apoptosis and cell cycle of thymocytes are analyzed by flow cytometry with annexin V-FITC/PI staining and PI staining.
The mechanisms of the radioprotective effects of PSP pigments are explored. The antioxidative effects of PSP pigments are detected. DCFH-DA fluorescent probe is applied to investigate the intra-cellular ROS. The activities of antioxidative enzymes SOD and GSH-px are detected by biochemistry methods. The effects of PSP pigments on mitochondrion-mediated apoptosis are analyzed. Mitochondrial membrane potential is detected by JC-1 fluorescent probe. The released cytochrome C, caspase 3, PARP, Bcl-2 and Bax proteins are investigated by western-blot. The enzyme activities of caspase 3 and caspase 9 are also detected. The effects of PSP pigments on death receptor-mediated apoptosis are determined by Fas mRNA RT-PCR analysis, FADD protein western-blot analysis and caspase 8 enzyme activity detection. The MAPK pathways including ERK, JNK and p38MAPK are analyzed by western-blot. The effects of PSP pigments on p53 are determined by p53 mRNA RT-PCR detection and p53, p21Cip1 and p27Kip1 protein western-blot analysis.
Results: MTT showes that ~(60)Coγray decreases the cell viabilities and a sharp decline of cell viability starts from 4h post-irradiation. 4Gy irradiation causes approximate 50% cell viability loss at 4h after ~(60)Coγray irradiation. So the ~(60)Co-irradiating model should be established at 4h post-4Gy-irradiation. With 4Gy irradiation, the cell viablities are increased in the present of 0.625g/L～2.500g/L PSP pigments in a concentration-dependent manner and no cytotoxcity is observed in these PSP pigments concentrations. DNA ladders are smeared and weak in PSP pigments pretreated groups compared to that of the irradiated group. Flow cytometry results show that PSP pigments can decrease the early apoptosis and attenuate the cell cycle arrest induced by irradiation.
The mechanisms of radioprotective effects of PSP pigments are explored and the results demonstrate that PSP pigments can decrease the intra-cellular ROS and increase the activities of SOD and GSH-px as well. PSP pigments stabilize the mitochondrial membrane potential, decrease the released cytochrome C, caspase 3 and PARP proteins. The activities of caspase 3 and caspase 9 are inhibited by PSP pigments. Bcl-2 protein is increased by PSP pigments while Bax is decreased to draw the cells towards antiapoptosis. PSP pigments show no significant effect on Fas mRNA and FADD protein but the activity of caspase 8 is increased in the present of medium and large dose of PSP pigments. MAPK pathway including JNK and p38MAPK is inhibited by PSP pigments but no changes happen to ERK. P53 mRNA and p53 protein are both depressed by PSP pigments and p27Kip1 is decreased consequently to attenuate the cell cycle arrest. PSP pigments have no obvious effects on p21Cip1 protein.
Conclusion: PSP pigments can inhibit the ~(60)Coγray-induced damage in murine thymocytes. The cell viability is increased, apoptosis is decreased and cell cycle arrest induced by irradiation is attenuated in the present of PSP pigments. The radioprotective effects are related to the anti-oxidative effects of PSP pigments, which scavenging the intra-cellular ROS and enhancing the activities of anti-oxidative enymes to rebanlance the redox. The mitochondrial-mediated apoptosis pathway but not the death receptor-mediated apoptosis pathway is inhibited by PSP pigments. Bcl-2 and Bax are involved in the anti-apoptosis effects of PSP pigments. PSP pigments depress JNK and p38MAPK pathways but keep no influence on ERK. P53 mRNA is inactivated and p53 protein is decreased by PSP pigments pretreatment. Cell cycle arrest related p53 flare-up is cooling down by PSP pigments and p27Kip1 but not p21Cip1 is consequently decreased. Thus, the radio-protective effects of PSP pigments are via modulation of multiple genes and proteins to yield the anti-oxidation, anti-apoptosis and anti-cell cycle arrest. The PSP pigments might become a promising candidate for radio-protector.
方法建立紫薯素干预~(60)Coγ辐射小鼠胸腺细胞的模型。应用MTT,首先检测~(60)Coγ辐射在0～12h范围内对小鼠胸腺细胞活力的影响,~(60)Co分为0,2,4,6Gy四个不同剂量进行单次辐射。不同剂量的紫薯素预处理细胞,MTT检测紫薯素对辐射细胞活力的影响、抗辐射的有效剂量以及其有无毒性反应。紫薯素对辐射细胞的作用检测中,通过DNA ladder检测细胞晚期凋亡;以流式细胞仪Annexin V-FITC/PI染色检测细胞早期凋亡;流式细胞仪PI染色检测细胞周期。
探讨紫薯素辐射防护作用的机制。测定紫薯素对氧化应激的影响:2,7-二氯氢化荧光素二酯(DCFH-DA)为荧光探针,检测紫薯素对~(60)Co照射后细胞内活性氧(ROS)的影响;酶生化法测定抗氧化酶过氧化物歧化酶(SOD)和谷胱甘肽过氧物酶(GSH-px)的活力。研究紫薯素对~(60)Co诱导小鼠胸腺细胞凋亡的线粒体通路的影响:JC-1荧光染色测定线粒体膜电位;western-blot检测细胞色素C、caspase3和PARP的蛋白表达以及Bcl-2和Bax的蛋白表达;对caspase 3和caspase 9进行酶活性检测。研究紫薯素对~(60)Co诱导小鼠胸腺细胞凋亡的死亡受体通路的影响:RT-PCR检测Fas mRNA;western-blot测定FADD的蛋白表达;caspase8酶活性的检测。检测紫薯素对~(60)Co诱导小鼠胸腺细胞的MAPK途径的影响:western-blot测定磷酸化的ERK、JNK、p38MAPK的蛋白表达。探讨紫薯素对~(60)Co诱导小鼠胸腺细胞p53的影响:RT-PCR检测p53 mRNA;Western-blot检测p53、p21Cip1和p27Kip1的蛋白表达。
结果MTT结果显示: ~(60)Coγ辐射作用于细胞,降低了细胞活力;辐射各组细胞活力从4h开始急剧衰减。4Gy辐射后4h的细胞活力接近50%。本研究选择了4Gy辐射后4h建立细胞损伤模型。辐射后,在0.625g/L～2.500g/L浓度范围内,紫薯素能够提升辐射小鼠胸腺细胞的活力,其提升细胞活力的能力与剂量呈量效依赖关系,而且在此剂量范围内,紫薯素对细胞无毒性。DNA ladder显示:辐射后小鼠胸腺细胞产生明显的ladder,紫薯素干预使DNA ladder减弱。流式检测显示:紫薯素降低了辐射导致的小鼠胸腺细胞早期凋亡,同时缓解了辐射导致的G2/M期细胞周期阻滞。
紫薯素的防辐射机制试验结果显示:紫薯素降低了细胞内ROS的含量,提高了抗氧化酶SOD与GSH-px的活性;稳定了线粒体膜电位,减少细胞色素C的释放,降低caspase 3和PARP的蛋白表达,抑制caspase 9和caspase 3的酶活性,并使Bcl-2蛋白表达升高而Bax蛋白表达降低;对Fas mRNA和FADD蛋白表达无显著作用,但中、高剂量的紫薯素对caspase 8的酶活性有一定的提升;MAPK通路中,紫薯素对ERK活性的影响不明显,对磷酸化的JNK和p38MAPK表达有显著的抑制作用;紫薯素提高p53 mRNA与p53的蛋白表达,抑制p27Kip1的蛋白表达,对p21Cip1蛋白表达的作用不明显。
结论:紫薯素能够有效地抑制~(60)Co辐射引起的小鼠胸腺细胞损伤,提高细胞活力,抑制细胞凋亡,缓解细胞周期阻滞。紫薯素的辐射防护机制包括:抑制了由~(60)Co辐射诱导的细胞氧化损伤,降低ROS,提高抗氧化酶的活性,通过改善氧化还原状态抑制辐射诱导的凋亡;抑制线粒体凋亡信号通路,同时调节Bcl-2、Bax蛋白达到抑制凋亡的目的;对死亡受体凋亡信号通路无作用;MAPK途径中,抑制了JNK与p38MAPK磷酸化,对ERK活性没有影响;通过抑制p53的转录激活和蛋白表达,抑制辐射导致的细胞凋亡;通过抑制p53以及其下游的p27Kip1,缓解细胞周期阻滞。紫薯素通过调节多种基因与蛋白的表达,达到其抗氧化、抗凋亡、缓解细胞周期阻滞的辐射防护作用,有望成为应用广泛的~(60)Co辐射防护剂。
Objective: Establish the ~(60)Coγray-induced irradiation damage model in murine thymocytes. Investigate the protective effects of purple sweet potato(PSP)pigments on ~(60)Co-induced damage.
Methods: After ~(60)Coγray-single dose-irradiation with various doses of 0, 2, 4, 6Gy, the murine thymocytes viabilities are detected by MTT at the post-irradiated time point ranged from 0 to 12h. Treated the thymocytes with indicated dose of irradiation in the present of different concentrations of PSP pigments, the cell viabilities are detected by MTT to investigate the effective and safe concentrations of PSP pigments against irradiation. After the model of PSP pigments against irradiaion is established, DNA ladder is preformed to test whether PSP pigments have the protective effect on late apoptosis. The early apoptosis and cell cycle of thymocytes are analyzed by flow cytometry with annexin V-FITC/PI staining and PI staining.
The mechanisms of the radioprotective effects of PSP pigments are explored. The antioxidative effects of PSP pigments are detected. DCFH-DA fluorescent probe is applied to investigate the intra-cellular ROS. The activities of antioxidative enzymes SOD and GSH-px are detected by biochemistry methods. The effects of PSP pigments on mitochondrion-mediated apoptosis are analyzed. Mitochondrial membrane potential is detected by JC-1 fluorescent probe. The released cytochrome C, caspase 3, PARP, Bcl-2 and Bax proteins are investigated by western-blot. The enzyme activities of caspase 3 and caspase 9 are also detected. The effects of PSP pigments on death receptor-mediated apoptosis are determined by Fas mRNA RT-PCR analysis, FADD protein western-blot analysis and caspase 8 enzyme activity detection. The MAPK pathways including ERK, JNK and p38MAPK are analyzed by western-blot. The effects of PSP pigments on p53 are determined by p53 mRNA RT-PCR detection and p53, p21Cip1 and p27Kip1 protein western-blot analysis.
Results: MTT showes that ~(60)Coγray decreases the cell viabilities and a sharp decline of cell viability starts from 4h post-irradiation. 4Gy irradiation causes approximate 50% cell viability loss at 4h after ~(60)Coγray irradiation. So the ~(60)Co-irradiating model should be established at 4h post-4Gy-irradiation. With 4Gy irradiation, the cell viablities are increased in the present of 0.625g/L～2.500g/L PSP pigments in a concentration-dependent manner and no cytotoxcity is observed in these PSP pigments concentrations. DNA ladders are smeared and weak in PSP pigments pretreated groups compared to that of the irradiated group. Flow cytometry results show that PSP pigments can decrease the early apoptosis and attenuate the cell cycle arrest induced by irradiation.
The mechanisms of radioprotective effects of PSP pigments are explored and the results demonstrate that PSP pigments can decrease the intra-cellular ROS and increase the activities of SOD and GSH-px as well. PSP pigments stabilize the mitochondrial membrane potential, decrease the released cytochrome C, caspase 3 and PARP proteins. The activities of caspase 3 and caspase 9 are inhibited by PSP pigments. Bcl-2 protein is increased by PSP pigments while Bax is decreased to draw the cells towards antiapoptosis. PSP pigments show no significant effect on Fas mRNA and FADD protein but the activity of caspase 8 is increased in the present of medium and large dose of PSP pigments. MAPK pathway including JNK and p38MAPK is inhibited by PSP pigments but no changes happen to ERK. P53 mRNA and p53 protein are both depressed by PSP pigments and p27Kip1 is decreased consequently to attenuate the cell cycle arrest. PSP pigments have no obvious effects on p21Cip1 protein.
Conclusion: PSP pigments can inhibit the ~(60)Coγray-induced damage in murine thymocytes. The cell viability is increased, apoptosis is decreased and cell cycle arrest induced by irradiation is attenuated in the present of PSP pigments. The radioprotective effects are related to the anti-oxidative effects of PSP pigments, which scavenging the intra-cellular ROS and enhancing the activities of anti-oxidative enymes to rebanlance the redox. The mitochondrial-mediated apoptosis pathway but not the death receptor-mediated apoptosis pathway is inhibited by PSP pigments. Bcl-2 and Bax are involved in the anti-apoptosis effects of PSP pigments. PSP pigments depress JNK and p38MAPK pathways but keep no influence on ERK. P53 mRNA is inactivated and p53 protein is decreased by PSP pigments pretreatment. Cell cycle arrest related p53 flare-up is cooling down by PSP pigments and p27Kip1 but not p21Cip1 is consequently decreased. Thus, the radio-protective effects of PSP pigments are via modulation of multiple genes and proteins to yield the anti-oxidation, anti-apoptosis and anti-cell cycle arrest. The PSP pigments might become a promising candidate for radio-protector.
引文
[1]Bhide SA, Nutting CM. Advances in radiotherapy for head and neck cancer [published online ahead of print April 19, 2010]. Oral Oncol.
[2]Oh YT, Kim CH, Choi JH, et al. Sensory neural hearing loss after concurrent cisplatin and radiation therapy for nasopharyngeal carcinoma. Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology, 2004, 72:79–82.
[3]Sonis ST, Elting LS, Keefe D, et al. Perspectives on cancer therapy-induced mucosal injury: Pathogenesis, measurement, epidemiology, and consequences for patients. Cancer, 2004,100: 1995–2025.
[4]雷筱芬,陈木森.黄酮类化合物抗辐射研究进展.江西农业大学学报,2007,29(6):1039-1042.
[5]段伟,毕良文,秦继勇,等.辐射防护药物研究进展.中国辐射卫生,2006,15(1):l14-115.
[6]王岳飞,唐德松,朴宰日,等.茶多酚对荷瘤小鼠辐射损伤的影响.中华放射医学与防护杂志,2004,24(3):263.
[7]吕秋军,温利青,张敏,等.白藜芦醇的辐射防护及其分子机理的研究.中华放射医学与防护杂志,2004,24(1):21.
[8]孙维琦,郭英,张义全,等.大豆异黄酮与大豆皂甙抗辐射作用的实验研究.中国辐射卫生,2007,16(3):273-274.
[9]李德远,周韫珍,余应利,等.银杏叶黄酮抗辐射效应研究.营养学报,2004,26(3):220-222.
[10]Goda Y, Shimizu T, Kato Y, et al. Two acylated anthocyanins from purple sweet potato. Phytochemistry, 1997,44(1):183~186
[11] Terahara N, Konczak Islam I, Nakatani M, et al. Anthocyanins in callus induced from purple storage root of Ipomoea batatas L. Phytochemistry, 2000,54(8):919~922
[12]陈勇,张晴.AB-8大孔吸附树脂吸附和分离甘薯紫色素的研究.中国食品添加剂, 2001,(1):6~9
[13]沈勇根,上官新晨,徐明生,等.紫红薯色素的提取和精制.江西农业大学学报.2004,26(6):912~916
[14]Islam MS, Yoshimoto M, Terahara N, et al. Anthocyanin compositions in sweetpotato(Ipomoea batatas L.) leaves. Bioscience, Biotechnology, and Biochemistry,2002,66:2483–2486.
[15]Terahara N, Konczak I, Ono H, et al. Characterization of acylated anthocyanins in callus induced from storage root of purple-fleshed sweet potato, Ipomoea batatas L. Journal of Biomedicine & Biotechnology, 2004,2004:279–286.
[16]Suda I, Oki T, Masuda M, et al. Direct absorption of acylated anthocyanin in purple-fleshed sweet potato into rats. Journal of Agriculture and Food Chemistry. 2002,50(6):1672~1676
[17]姜平平,吕晓玲.紫心甘薯花色苷抗氧化活性体外实验研究.中国食品添加剂,2002,(6):8~11
[18]吕晓玲,孙晓侠,姚秀玲.采用荧光化学发光法分析紫甘薯花色苷产品的抗氧化作用.食品与发酵工业, 2005,31(9):53~55
[19]Kano M, Takayanagi T, Harada K, et al. Antioxidative activity of anthocyanins from purple sweet potato, Ipomoera batatas cultivar Ayamurasaki. Bioscience, Biotechnology, and Biochemistry, 2005,69:979–988.
[20]Yoshimoto M, Okuno S, Yamaguchi M, et al. Antimutagenicity of decylated anthocyanins in purple-fleshed sweet potato. Bioscience-Biotechnology And Biochemistry. 2001, 65(7):1652~1655
[21]Brown DQ, Pittock JW 3rd, Rubinstein JS. Early results of the screening program for radioprotectors. Int. J. Radiat. Oncol. Biol. Phys., 1982, 8, 565–570
[22] Cassatt DR, Fazenbaker CA, Bachy CM, et al. Preclinical modeling of improved amifostine (ethyol) use in radiation therapy. Semin. Radiat. Oncol. 2002, 12, 97–102
[23] Koukourakis MI, Kyrias G, Kakolyris S, et al. Subcutaneous administration of amifostine during fractionated radiotherapy: a randomized phase II study. J. Clin. Oncol. 2000,18, 2226–2233
[24] Whitnall MH, Elliott TB, Harding RA, et al. Androstenediol stimulates myelopoiesis and enhances resistance to infection in gamma-irradiated mice. Int. J. Immunopharmacol. 2000, 22, 1–14
[25] Landauer MR, Srinivasan V, Seed TM, et al. Genistein treatment protects mice from ionizing radiation injury. J. Appl. Toxicol. 2003, 23, 379–385
[26]Karbownik, M. and Reiter, R.J. Antioxidative effects of melatonin in protection against cellular damage caused by ionizing radiation. Exp. Biol. Med. 2000, 225: 9–22
[27]Nair CKK, Parida DK, Nomura T. Radioprotectors in Radiotherapy. J Radiat Res 2001;42 :21–37.
[28]Gopal R, Tucker SL, Komaki R, et al. The relationship between local dose and loss of function for irradiation lung. I J R O B P, 2003, 56(1):106-113.
[29]Marks LB. Dosimetric predictors of radiation-induced lung injury. I JROBP 2002, 54(2):313–316.
[30]Brown JM, Wilson WR. Exploiting tumour hypoxia in cancer treatment. Nat Rev Cancer 2004,4:437–447.
[31]Le Q-T. Identifying and targeting hypoxia in head and neck cancer: A brief overview of current approaches. Int J Radiation Oncology Biol Phys 2007, 69(2 Supplement):S56–S58.
[32]Bayir H, Fadeel B, Palladino MJ, et al. Apoptotic interactions of cytochrome c: Redox flirting with anionic phospholipids within and outside of mitochondria. Biochimica et Biophysica Acta 2006,1757:648–659.
[33]Kagan VE, Tyrina YY, Bayir H, et al. The“pro-apoptotic genies”get out of mitochondria: Oxidative lipidomics and redox activity of cytochrome c/cardiolipin complexes. Chem Biol Interact 2006,163:15–28.
[34]Anscher MS, Kong FM, Andrews K, et al. Plasma TFG,1 as a predictor of radiation pneumonitis. I JROBP 1998,41:1029–1035.
[35]Rubin P, Johnston CJ, Williams JP, et al. A perpetual cascade of cytokines postirradiation leads to pulmonary fibrosis. Int J Radiat Oncol Bio Phys 1995, 33:99–109.
[36]Mendonca MS, Mayhugh BM, McDowell B, et al. A radiation-induced acute apoptosis involving TP53 and BAX precedes the delayed apoptosis and neoplastic transformation of CGL1 human hybrid cells. Rad Res, 2005,163:614–622.
[37]Maiuri MC, Zalckvar E, Kimchi A, et al. Self-eating and self-killing: crosstalk between autophagy and apoptosis. Nature Reviews: Mol Cell Bio, 2007, 8:741–748.
[38]Niu Y, Epperly MW, Shen H, et al. Intraesophageal MnSOD-plasmid liposome administration enhances engraftment and self-renewal capacity of bone marrow derived progenitors of esophageal squamous epithelium. Gene Therapy, 2008, 15:347–356.
[39]Li X-M, Hu Z, Jorgenson ML, et al. Bone marrow sinusoidal endothelial cells undergo nonapoptotic cell death and are replaced by proliferating sinusoidal cells in situ to maintain thevascular niche following lethal irradiation. Exper Hematol, 2008, 36:1143–1156.
[40]Ricardo SD, van Goor H, HedíAA. Macrophage diversity in renal injury and repair. J Clin Inves, 2008,118:3522–3529.
[41]Belkacemi Y, Labopin M, Hennequin C, et al. Reduced-intensity conditioning regimen using low-dose total body irradiation before allogeneic transplant for hematologic malignancies: Experience from the European group for blood and marrow transplantation. Int J Rad Oncol Biol Phys, 2007, 67:544–551.
[42]Wong JYC, Liu A, Schultheiss T, et al. Targeted total marrow irradiation using three-dimensional image-guided tomographic intensitymodulated radiation therapy: An alternative to standard total body irradiation. Biol Blood Marrow Transplant, 2006,12:306–315.
[43]Sorror ML, Storer BE, Maloney DG, et al. Outcomes after allogeneic hematopoietic cell transplantation with nonmyeloablative conditioning regimens for treatment of lymphoma and chronic lymphocytic leukemia. Blood, 2008, 111:446–452.
[44]Rotblat J, Lindop P. Long-term effects of a single whole-body exposure of mice to ionizing radiations. II. Causes of death. Proc R Soc Lond, 1961, 154:350–368.
[45]Haupt R, Fears TR, Robison LL, et al. Educational attainment in long-term survivors of childhood acute lymphoblastic leukemia. JAMA, 1994, 272:1427–1432.
[46]Van Dongen-Melman JEWM, De Groot A, Van Dongen JJM, et al. Cranial irradiation is the major cause of learning problems in children treated for leukemia and lymphoma: A comparative study. Leukemia, 1997, 11:1197–1200.
[47]Laack NN, Brown PD, Ivnik RJ, et al. Cognitive function after radiotherapy for supratentorial low-grade glioma: A north central cancer treatment group prospective study. Int J Rad Oncol Biol Phys, 2005,63(4):1175–1183.
[48]Zhou S, Greenberger JS, Epperly MW, et al. Age-related intrinsic changes in human bone marrow-derived mesenchymal stem cells and their differentiation to osteoblasts. Aging Cell, 2008, 7:335–343.
[49]Epperly MW, Dixon T, Wang H, et al. Modulation of radiation-induced life shortening by systemic intravenous MnSOD-plasmid liposome gene therapy. Rad Res, 2008, 170:437–443.
[50]Little, J.B. Radiation carcinogenesis. Carcinogenesis, 2000, 21, 397–404
[51]Muramoto GG, Chen B, Cui X, et al. Vascular endothelial cells produce soluble factors that mediate the recovery of human hematopoietic stem cells after radiation injury. Biol Blood Marrow Transplant, 2006,12:530–540.
[52]Chute JP, Muramoto GG, Salter AB, et al. Transplantation of vascular endothelial cells mediates the hematopoietic recovery and survival of lethally irradiated mice. Blood, 2007, 109:2365–2372.
[53]Dai Y, Grant S. Targeting multiple arms of the apoptotic regulatory machinery. Cancer Res, 2007,67:2908–2911.
[54]Gardai SJ, Bratton DL, Ogden CA, et al. Recognition ligands on apoptotic cells: a perspective. J Leukoc Bio, 2006,79:896–903.
[55]Seed TM, Kaspar LV. Probing altered hematopoietic progenitor cells of preleukemic dogs with JANUS fission neutrons. Rad Res, 1991,128:S81–S86.
[56]Seed TM, Kaspar LV, Grdina DJ. Hematopoietic repair modifications during preclinical phases of chronic radiation-induced myeloproliferative disease. Exp Hematol ,1986,14 :433.
[57]Seed TM, Kaspar LV. Changing patterns of radiosensitivity of hematopoietic progenitors from chronically irradiated dogs prone either to aplastic anemia or to myeloproliferative disease. Leukemia Res ,1990,14:299–307.
[58]Seed TM, Kaspar LV, Tolle DV, et al. Chronic radiation leukemogenesis : Postnatal hematopathologic effects resulting from in-utero irradiation. Leukemia Res, 1987,11 :171–179.
[59]Seed TM, Carnes BA, Tolle DV, et al. Blood responses under chronic low daily dose gamma irradiation: I. Differential preclinical responses of irradiated male dogs in progression to either aplastic anemia or myeloproliferative disease. Leukemia Res, 1989,13 :1069–1084.
[60]Kang SK, Rabbani ZN, Folz RJ, et al. Overexpression of extracellular superoxide dismutase protects mice from radiation-induced lung injury. I J R O B P , 2003, 57:1056–1066.
[61]Greenberger, JS.; Epperly, MW. Pleiotrophic stem cell and tissue effects of ionizing irradiation protection by MnSOD-plasmid liposome gene therapy. In: Redberry, GW., editor. Gene Therapy in Cancer. Nova Science Publishers, Inc; 2005. p. 191-215.
[62]Gorbunov NV, Poque-Geile KL, Epperly MW, et al. Activation of the nitric oxide synthase 2 pathway in the response of bone marrow stromal cells to high doses of ionizing radiation. Rad Res, 2000,154:73–86.
[63]Constine LS, Tarbell N, Hudson MM, et al. Subsequent malignancies in children treated for Hodgkin’s disease: Associations with gender and radiation dose. Int J Rad Onc Biol Phys, 2008, 72:24–33.
[64]Romanik EA, Leif J, Sakakeeny MA, et al. Sequence analysis of mutational hot spots in the endogenous and transfected CSF-1 receptor in gamma-irradiation induced factor-independent subclones of clonal hematopoietic progenitor cell lines. Radiat Oncol Invest: Clin Bas Res ,1993, 1:94–102.
[65]Wang J, Zheng H, Ou X, et al. Deficiency of microvascular thrombomodulin and upregulation of protease-activated receptor-1 in irradiated rat intestine. Possible link between endothelial dysfunction and chronic radiation fibrosis. Am J Pathol , 2002,160:2063–2070.
[66]Flanders KC, Sullivan CD, Fujii M, et al. Mice lacking Smad3 are protected against cutaneous injury induced by ionizing radiation. Am J Pathol, 2002, 160:1057–1068.
[67]Anzano MA, Mitchell JB, Russo A, et al. Interference with transforming growth factor-beta/Smad3 signaling results in accelerated healing of wounds in previously irradiated skin. Am J Pathol ,2003, 163:2247–2257.
[68]Dileto CL, Travis EL. Fibroblast radiosensitivity in vitro and lung fibrosis in vivo: Comparison between a fibrosis-prone and fibrosis-resistant mouse strain. Rad Res, 1996,146:61–67.
[69]Kanai A, Epperly M, Pearce L, et al. Differing roles of mitochondrial nitric oxide synthase in cardiomyocytes and urothelial cells. Am J Physiol Heart Circ Physiol, 2004,286:H13–H21.
[70]Safwat A, Bentzen SM, Turesson I, et al. Deterministic rather than stochastic factors explain most of the variation in the expression of skin telangiectasia after radiotherapy. Int J Radiat Oncol Biol Phys, 2002, 52:198–204.
[71]Moulder JE, Cohen EP. Future strategies for mitigation and treatment of chronic radiation-induced normal tissue injury. Semin Rad Onco, 2007, 17:141–148.
[72]Moulder JE, Fish BL, Cohen EP. Treatment of radiation nephropathy with ACE inhibitors and AII type-1 and type-2 receptor antagonists. Current Pharm Design, 2007, 13 :1317–1325.
[73]Cohen EP, Irving AA, Drobyski WR, et al. Captopril to mitigate chronic renal failure after hematopoietic stem cell transplantation: a randomized controlled trial. Int J Rad Oncol Biol Phys, 2008, 70:1546–1551.
[74]Mothersill C, Seymour C. Radiation-induced bystander effects: Past history and future directions. Rad Res, 2001, 155:759–767.
[75]Stone HB, Moulder JE, Coleman CN, et al. Models for evaluating agents intended for the prophylaxis, mitigation, and treatment of radiation injuries. Rad Res , 2004, 162:711–718.
[76] Hosseinimehr SJ, Zakaryaee V, Froughizadeh M, et al. Oral oxymetholone reduces mortality induced by gamma irradiation in mice through stimulation of hematopoietic cells. Mol. Cell. Biochem. 2006, 287, 193–199
[77]Zhou, Y. and Mi, M.T. Genistein stimulates hematopoiesis and increases survival in irradiated mice. J. Radiat. Res. 2005, 46, 425–433
[78]Dainiak, N. Hematologic consequences of exposure to ionizing radiation. Exp. Hematol. 2002, 30, 513–528
[79]Qiu Wei C-W, Carson-Walter EB, Liu H, et al. PUMA regulates intestinal progenitor cell radiosensitivity and gastrointestinal syndrome. Cell, Stem Cell , 2008, 2:576–583.
[80]Morgan JL, Holcomb TM, Morrissey RW. Radiation reaction in ataxia telangiectasia. Am J Dis Child ,1968, 116:557–558.
[81] Ho AY, Atencio DP, Peters S, et al. Genetic predictors of adverse radiotherapy effects: The Gene-PARE project. Int J Radiat Oncol Biol Phys, 2006, 65:646–655.
[82]Shiloh Y. ATM and related protein kinases: Safeguarding genome integrity. Nat Rev Cancer, 2003, 3:155–168.
[83]Abraham RT. Cell cycle checkpoint signaling through the ATM and ATR kinases. Genes Dev, 2001, 15:2177–2196.
[84]Casado JA, Nunez MI, Segovia JC, et al. Non-homologous end-joining defect in fanconi anemia hematopoietic cells exposed to ionizing radiation. Rad Res , 2005, 164:635–641.
[85] Taniguchi T, Garcia-Hiquera I, Xu B, et al. Convergence of the fanconi anemia and ataxia telangiectasia signaling pathways. Cell ,2002, 109:459–472.
[86]Marcou Y, D’Andrea A, Jeggo PA, et al. Normal cellular radiosensitivity in an adult Fanconi anemia patient with marked clinical radiosensitivity. Radiother Oncol, 2001, 60 :75–79.
[87]Imamura O, Fujita K, Itoh C, et al. Werner and Bloom helicases are involved in DNA repair in a complementary fashion. Oncogene, 2002, 21 :954–963.
[88]Imamura O, Campbell JL. The human Bloom syndrome gene suppresses the DNA replicationand repair defects of yeast dna2 mutants. Proc Natl Acad Sci USA ,2003,100:8193–8198.
[89]Maisin, J.R. Bacq and Alexander award lecture chemical radioprotection: past, present and future prospects. Int. J. Radiat. Biol. 1998, 73, 443–450
[90]Greenberger JS, Epperly MW, Gretton J, et al. Radioprotective gene therapy. Curr Gene Ther 2003;3:183–195.
[91]Greenberger JS, Epperly MW. Radioprotective antioxidant gene therapy: Potential mechanisms of action. Gene Ther Mol Biol, 2004, 8:31–44.
[92]Gandhi NM, Nair CKK. Radiation protection by diethyldithiocarbamate: protection of membrane and DNA in vitro and in vivo againstγ-irradiation. J. Radiat. Res, 2004, 45:175–180.
[93]Yuhas JM, Davis ME, Glover D, et al. Circumvention of the tumor membrane barrier to WR-2721 absorption by reduction of the drug hydrophilicity. Int. J. Radiat. Oncol, 1982, 8:519–522.
[94]Anscher MS, Chen L, Rabbani Z, et al. Recent progress in defining mechanisms and potential targets for prevention of normal tissue injury after radiation therapy. Int. J. Radiat. Oncol. Biol. Phys, 2005, 62:255–259.
[95]Epperly MW, Bray J, Kraeger S, et al. Prevention of late effects of irradiation lung damage by manganese superoxide dismutase gene therapy. Gene Ther, 1998, 5:196–208.
[96]Vujaskovic Z, Batinic-Haberle I, Rabbani ZN, et al. A small molecule weight catalytic metalloporphyrin antioxidant with superoxide dismutase (SOD) mimetic properties protects lungs from radiation-induced injury. Free Rad. Biol. Med, 2002, 33:857–863.
[97]Lefaix J-L, Delanian S, Leplat J-J, et al. Successful treatment of radiation-induced fibrosis using Cu/Zn-SOD and Mn-SOD: an experimental study. Int. J. Radiat. Oncol. Biol. Phys, 1996, 35:305–312.
[98]Lin Z, Nei M, Ma H. The origins and early evolution of DNA mismatch repair genes-multiple horizontal gene transfers and co-evolution. Nucleic Acids Res, 2007, 35:7591–7603.
[99]Bennett CB, Lewis LK, Karthikeyan G, et al. Genes required for ionizing radiation resistance in yeast. Nat Genet, 2001, 29 :426–434
[100]Cox MC, Battista JR. Deinococcus radiodurans the consummate survivor. Nature Reviews: Micro, 2005, 3:882–892.
[101]Daly MJ, Gaidamakova EK, Matrosova VY, et al. Accumulation of Mn(II) in deinococcus radiodurans facilitates gamma-radiation resistance. Science, 2004, 306:1025–1030.
[102]Zheng S, Newton GL, Ward JF, et al. Aerobic radioprotection of pBR322 by thiols: effect of thiol net charge upon scavenging of hydroxyl radicals and repair of DNA radicals. Radiat. Res, 1992, 130:183–193.
[103]Kumar SS, Devasagayam TPA, Jayshree B, et al. Mechanism of protection against radiation-induced DNA damage in plasmid pBR322 by caffeine. Int. J. Radiat. Biol, 2001, 77:617–623.
[104]Reiter RJ, Tan D, Mayo JC, et al. Melatonin as an antioxidant: biochemical mechanisms and pathophysiological implications in humans. Acta. Biochem. Pol, 2003, 50:1129–1146.
[105]Maurya DK, Salvi VP, Nair CKK. Radioprotection of normal tissues in tumor-bearing mice by troxerutin. J. Radiat. Res, 2004, 45:221–228.
[106]Uma Devi P, Bisht KS, Vinitha M. A comparative study of radioprotection by Ocimum flavonoids and synthetic animothiol protectors in the mouse. Brit. J. Radiol, 1998, 71:782–784.
[107]Weiss JF, Landauer MR. Protection against ionizing radiation by antioxidant nutrients and phytochemicals. Toxicology ,2003,189:1–20.
[108]Frei B, Higdon JV. Antioxidant activity of tea polyphenols in vivo: evidence from animal studies. J. Nutr, 2003, 133:3275S–3284S.
[109]Murley JS, Kataoka Y, Cao D, et al. Delayed radioprotection by NFκB-mediated induction of SOD2 (MnSOD) in SA-NH tumor cells after exposure to clinically used thiol-containing drugs. Radiat. Res, 2004, 162:536–546.
[110]Murley JS, Kataoka Y, Weydert CJ, et al. Delayed radioprotection by nuclear transcription factorκB-mediated induction of manganese superoxide dismutase in human microvascular endothelial cells after exposure to the free radical scavenger, WR1065. Free Rad. Biol. Med, 2006, 40:1004–1016.
[111]Wispe JR, Warner BB, Clark JC, et al. Human MnSOD in pulmonary epithelial cells of transgenic mice confers protection from oxygen injury. J Biol Chem, 1992, 267:23937–23941.
[112]Zhang X, Epperly MW, Kay MA, et al. Radioprotection in vitro and in vivo by minicircle plasmid carrying the human manganese superoxide dismutase transgene. Hum Gene Ther ,2008,19:820–826.
[113]Gauter-Fleckenstein B, Fleckenstein K, Owzar K, et al. Comparison of two Mn porphyrin-based mimics of superoxide dismutase in pulmonary radioprotection. Free Radic Biol Med, 2007, 44:982–989.
[114]Carpenter M, Epperly MW, Agarwal A, et al. Inhalation delivery of manganese superoxide dismutase-plasmid/liposomes (MnSOD-PL) protects the murine lung from irradiation damage. Gene Ther, 2005, 12:685–690.
[115]McClain DE, Kalinich JF, Ramakrishnan N. Trolox inhibits apoptosis in irradiated MOLT-4 lymphocytes. FASEB, 1995, 9:1345–1354.
[116]Fink M, Macias CA, Xiao J, et al. Hemigramicidin-TEMPO conjugates: Novel mitochondria-targeted antioxidants. Crit Care Med ,2007, 35:5461–5470
[117]Jiang J, Belikova NA, Hoye AT, et al. A mitochondria-targeted nitroxide/hemi-gramicidin S conjugate protects mouse embryonic cells againstγ-irradiation. I J R O B P ,2008,70:816–825.
[118]Amstad P, Peskin A, Shah G, et al. The balance between Cu, Zn-superoxide dismutase and catalase affects the sensitivity of mouse epidermal cells to oxidative stress. Biochemistry ,1991, 30:9305–9313.
[119]Rix-Montel MA. Biophysical aspects of radioprotectors by aminothiols. Engineering in Medicine and Biology Society, 1988, 2:1032–1033.
[120]Murley JS, Kataoka Y, Weydert CJ, et al. Delayed radioprotection by nuclear transcription factor kB-mediated induction of manganese superoxide dismutase in human microvascular endothelial cells after exposure to free radical scavenger WR1065. Free Radical Biol Med, 2006,40:1004–1016.
[121] Herceg Z, Milosvic Z, Kljajic R, et al. The effects of use of radioprotective compound WR-2721 on haematological parameters in lethally irradiated swines. YRPA, Proceedings of the 3rd Italian-Yugoslav Symposium on Radiation Protection; Plitvice, Yugloslavia. 1990. 30-35.
[122]Salganik RI. The benefits and hazards of antioxidants: controlling apoptosis and other protective mechanisms in cancer patients and the human population. J. Am. Coll. Nutr ,2001,20:464S–472S.
[123]Hernández-Flores G, Gómez-Contreras PC, Domínguez-Rodríguez JR, et al.γ-irradiationinduced apoptosis in peritoneal macrophages by oxidative stress. Implications of antioxidants in caspase mitochondrial pathway. Anticancer Res, 2005, 25:4091–4100.
[124]Kondo H, Park S-H, Watanabe K, et al. Polyphenol (?)-epigallocatechin gallate inhibits apoptosis induced by irradiation in human HaCaT keratinocytes. Biochem. Biophys. Res. Commun, 2004,316:59–64.
[125]Khodarev NN, Kataoka Y, Murley JS, et al. Interaction of amifostine and ionizing radiation on transcriptional patterns of apoptotic genes expressed in human microvascular endothelial cells (HMEC). Int. J. Radiat. Oncol. Biol. Phys, 2004, 60:553–563.
[126] Drouet M, Mourcin F, Grenier N, et al. Single administration of stem cell factor, FLT-3 ligand, megakaryocyte growth and development factor, and interleukin-3 in combination soon after irradiation prevents nonhuman primates from myelosuppression: longterm follow-up of hematopoiesis. Blood, 2004, 103, 878–885
[127] Hérodin F, Bourin P, Mayol JF, et al. Short-term injection of antiapoptotic cytokine combinations soon after lethal g-irradiation promotes survival. Blood, 2003, 101, 2609–2616
[128] Whitnall MH, Wilhelmsen CL, McKinney L, et al. Radioprotective efficacy and acute toxicity of 5-androstenediol after subcutaneous or oral administration in mice. Immunopharm. Immunotoxicol. 2002, 24, 595–626
[129]Rowinsky EK. Targeted induction of apoptosis in cancer management: The emerging role of tumor necrosis factor-related apoptosis-inducing ligand receptor activating agents. J Clin Oncol, 2005, 23:9394–9407.
[130]Grdina DJ, Murley JS, Kataoka Y, et al. Differential activation of nuclear transcription factor KB, gene expression, and proteins by amifostine’s free thiol in human microvascular endothelial and glioma cells. Semin Radiat Oncol, 2002,12:103–111.
[131]Baumann M, Krause M, Hill R. Exploring the role of cancer stem cells in radioresistance. Nature Reviews Cancer, 2008, 8:545–552.
[132]Held KD. and Biaglow, J. (1994) Mechanisms for the oxygen radical-mediated toxicity of various thiol-containing compounds in cultured mammalian cells. Radiat. Res. 139, 15–23
[133] Weiss JF, Kumar KS, Walden TL, et al. Advances in radioprotection through the use of combined agent regimens. Int. J. Radiat. Biol. 1990, 57, 709–722
[134]Holland J. New treatment modulation in radiation therapy. J. Infus. Nurs. , 2001,24, 95–101
[135]Mazur L. Radioprotective effects of the thiols GSH and WR-2721 against Xrays-induction of micronuclei in erythroblasts. Mutat. Res., 2000, 468, 27–33
[136]Spencer CM. and Goa, K.L. Amifostine, a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential as a radioprotector and cytotoxic chemoprotector. Drugs,1995, 50, 1001–1031
[137] AnnéPR, Machtay M, Rosenthal DI, et al. A phase II trial subcutaneous amifostine and radiation therapy in patients with head–neck cancer. Int. J. Radiat. Oncol. Biol. Phys. 2007, 67, 445–452
[138]Srinivasan V. Radioprotection, pharmacokinetic and behavioural studies in mouse implanted with biodegradable drug (amifostine) pellets. Int. J. Radiat. Biol. , 2002, 78, 535–543
[139] Ozsahin M, Betz M, Matzinger O, et al. Feasibility and efficacy of subcutaneous amifostine therapy in patients with head and neck cancer treated with curative accelerated concomitant-boost radiation therapy. Arch. Otolaryngol. Head Neck Surg. 2006, 132, 141–145
[140]Anne PR. and Curran WJ. A phase II trial of subcutaneous amifostine and radiation therapy in patients with head and neck cancer. Semin. Radiat. Oncol., 2002, 12, 18–19
[141] Maisin JR, Albert C, Henry A, et al. Reduction of short-term radiation lethality by biological response modifiers given alone or in association with other chemical protectors. Radiat. Res. 1993, 135(3), 332–337
[142] Landauer MR, Castro CA, Benson KA, et al. Radioprotective and locomotor responses of mice treated with nimodipine alone and in combination with WR-151327. J. Appl. Toxicol. 2001, 21, 25–31
[143]Seed TM. Radiation protectants: current status and future prospects. Health Phys., 2005, 89, 531–545
[144] Vitolo JM, Cotrim AP, Sowers AL, et al. The stable nitroxide tempol facilitates salivary gland protection during head and neck irradiation in a mouse model. Clin. Cancer Res. 2004, 10, 1807–1812
[145] Cotrim AP, Sowers AL, Lodde BM, et al. Kinetics of tempol for prevention of xerostomia following head and neck irradiation in a mouse model. Clin. Cancer Res. 2005, 11, 7564–7568
[146] Hahn SM, Krishna MC, DeLuca AM, et al. Evaluation of the hydroxylamine tempol-H as an in vivo radioprotector. Free Radic. Biol. Med. 2000, 28, 953–958
[147] Martin RF, Broadhurst S, Reum ME, et al. In vitro studies with methylproamine: a potent new radioprotector. Cancer Res. 2004, 64, 1067–1070
[148]Celaries, B. Synthesis and radioprotective study of new siladithioacetals and germadithioacetals. Appl. Organometal. 2003, 17, 561–569
[149] Martin RF, Broadhurst S, D'Abrew S, et al. Radioprotection by DNA ligands. Br. J. Cancer, 1996, 74, 99–101
[150] Epperly MW, Defilippi S, Sikora C, et al. Intratracheal injection of manganese superoxide dismutase (MnSOD) plasmid/liposomes protects normal lung but not orthopedic tumors from irradiation. Gene Ther. 2000, 7, 1011–1018
[151] Vujaskovic Z, Batinic-Haberle I, Rabbani ZN, et al. A small molecular weight catalytic metalloporophyrin antioxidant with superoxide dismutase (SOD) mimetic properties protects lung from radiation-induced injury. Free Radic. Biol. Med. 2002, 33, 857–863
[152] Guo H, Seixas-Silva JA Jr, Epperly MW, et al. Prevention of radiation-induced oral cavity mucositis by plasmid/liposome delivery of the human manganese superoxide dismutase (SOD2) transgene. Radiat. Res. 2003, 159, 361–370
[153] Epperly MW, Gretton JA, DeFilippi SJ, et al. Modulation of radiation-induced cytokine elevation associated with esophagitis and esophageal stricture by manganese superoxide dismutase-plasmide/liposome (SOD2-PL) gene therapy. Radiat. Res. 2001, 155, 2–14
[154] Epperly MW, Kagan VE, Sikora CA, et al. Manganese superoxide dismutase-plasmid/liposome (MnSOD-PL) administration protects mice from esophagitis associated with fractionated radiation. Int. J. Cancer, 2001, 96, 221–231
[155] Epperly MW, Carpenter M, Agarwal A, et al. Intraoral manganeses superoxide dismutase-plasmid/ liposome (MnSOD-PL) radioprotective gene therapy decreases ionizing irradiationinduced murine mucosal cell cycling and apoptosis. In Vivo, 2004, 18, 401–410
[156] Epperly MW, Wegner R, Kanai AJ, et al. Effects of MnSOD-plasmid liposome gene therapy on antioxidant levels in irradiated murine oral cavity orthopedic tumors. Radiat. Res. 2007, 167, 289–297
[157] Somack R, Saifer MG, Williams LD. et al. Preparation of long-acting superoxide dismutase using high molecular weight poly-ethylene glycol (41,000–72,000 Daltons). Free Radic. Res. Commun. 1991, 12–13, 553–562
[158] Vajragupta O, Boonchoong P, Sumanont Y, et al. Manganese-based complexes of radical scavengers as neuroprotective agents. Bioorg. Med. Chem. 2003, 11, 2329–2337
[159] Emami S, Hosseinimehr SJ, Taghdisi SM, et al. Kojic acid and its manganese and zinc complexes as potential radioprotective agents. Bioorg. Med. Chem. Lett. 2007, 17, 45–48
[160]Sorenson, J.R.J. Cu, Fe, Mn, and chelates offer a medicinal chemistry approach to overcoming radiation injury. Curr. Med. Chem. 2002, 9, 639–662
[161]Herodin F, and Drouet M. Cytokine-based treatment of accidentally irradiated victims and new approaches. Exp. Hematol., 2005, 33, 1071–1080
[162]于景敏,孟志云,窦桂芳.粒细胞集落刺激因子的研究新进展.中国实验血液学杂志,2008,16(2):452—456.
[163]克晓燕,贾廷珍,王继军,等.医源性急性放射病的l临床探讨.中华放射医学与防护杂志,2006,26(1):15—19.
[164] Kim JY, Oh SJ, Park HK, et al. Radioprotective effects of various cytokines in peripheral blood mononuclear cells and C3H mice. Oncol. Rep. 2005, 13, 1177–1183
[165] Hudak S, Leach MW, Xu Y, et al. Radioprotective effects of flk2/flt3 ligand. Exp. Hematol. 1998, 26, 515–522
[166] Jalal Hosseinimehr S, Inanami O, Hamasu T, et al. Activation of C-kit by stem cell factor induces radioresistance to apoptosis through ERK-dependent expression of survivin in HL60 cells. J. Radiat. Res. 2004, 45, 557–561
[167] LeguéF, Guitton N, Brouazin-Jousseaume V, et al. Il-6 key cytokine in vitro and in vivo response of sertoli cells to external gamma irradiation. Cytokine, 2001, 16, 232–238
[168] Neta R, Vogel SN, Oppenheim JJ, et al. Radioprotection with interleukin-1: comparison with other cytokines. Prog. Immunol. 1986, 6, 900–908
[169] Singh VK, Srinivasan V, Seed TM, et al. Radioprotection by N-palmitoylated nanopeptide of human interleukin-1b. Peptide ,2005, 26, 413–418
[170]Streeter PR. Activation of the G-CSF and Flt-3 receptors protects hematopoietic stem cells from lethal irradiation. Exp. Hematol. 2003, 31, 1119–1123
[171] Kashiwakura I, Inanami O, Takahashi K, et al. Protective effects of thrombopoietin and stem cell factor on x-irradiated CD34+ megakaryocytic progenitor cells from human placental and umbilical cord blood. Radiat. Res. 2003, 160, 210–216
[172] Patchen ML, MacVittie TJ, Brook I. et al. Glucan-induced hematopoietic and immune stimulation: therapeutic effects in sublethally and lethally irradiated mice. Meth. Find. Exp. Clin. Pharmacol. 1986, 8, 151–155
[173] Song JY, Han SK, Bae KG, et al. Radioprotective effects of ginsan, an immunomodulator. Radiat. Res. 2003, 159, 768–774
[174]Rya KG,McMinn A,Mitchell KA ,et a1.Mycosporine like amino acids in Antarctic sea ice algae,and their response to UVB radiation.Z Naturforsch,2002,57(5-6):471-477
[175]杜宁,高天翔,缪锦来,等.4种南极冰藻中抗紫外辐射活性化合物类菌胞素类氨基酸(MAAs)的初步研究.中国海洋药物杂志,2007,26(4):5-10
[176]吴晓曼,杨明亮,黄晓兰,等.海带多糖的抗辐射作用与脾细胞凋亡.武汉大学学报(医学版),2004,25(3):239-241
[177]吴显劲,孟庆勇,袁汉尧.琼枝麒麟菜多糖对辐射损伤小鼠腹腔巨噬细胞的影响.中国职业医学,2007,34(4):287-291
[178]吴显劲,孟庆勇.琼枝麒麟菜多糖对γ射线照射小鼠胸腺细胞周期及细胞增殖的影响.中国辐射卫生,2005,14(4):6-8
[179]吴显劲,盂庆勇.琼枝麒麟菜多糖对γ射线照射小鼠脾细胞周期及细胞增殖的影响.中国职业医学,2006,33(2):12—14
[180]王海青,李翊.海藻低聚糖对放射损伤的防护作用研究.中国辐射卫生,2009,18(1):33-35
[181]侯军峰,张盈华.中草药对造血和免疫系统放射损伤的防护作用及其机理探讨.中国中西医结合杂志,2000,20(6):469-472
[182]Kim IT,Park J,Nam JH,et a1.In-vitro and in-vivo anti-inflammatory and antinocieeptive efects of the methanol extract of the roots of Morinda ofieinalis.J Pharm Pharmacol,2005,57(5):607-615
[183] Stickney DR, Dowding C, Garsd A, et al. 5-Androstenediol stimulates multilineage hematopoiesis in rhesus monkeys with radiation-induced myelosuppression. Int. Immunopharmacol. 2006, 6, 1706–1713
[184] Stickney DR, Dowding C, Authier S, et al. 5-Androstenediol improves survival in clinically unsupported rhesus monkeys with radiation-induced myelosuppression. Int. Immunopharmacol. 2007, 7, 500–505
[185] Safeukui I, Mangou F, Malvy D, et al. Plasmodium bergheri: dehydroepiandrosterone sulfate reverses chloroquino-resistance in experimental malaria infection; correlation with glucose 6-phosphate dehydrogenase and glutathione synthesis pathway. Biochem. Pharmacol. 2004, 68, 1903–1910
[186]夏贞彪,王建国.中华放射医学与防护杂志,1994,14(5):322
[187]王月英,王汝勤,赵忠萍.中华放射医学与防护杂志,2005,25(1):39-40.
[188] Komarova EA, Chernov MV, Franks R, et al. Transgenic mice with p53-responsive lacZ: p53 activity varies dramatically during normal development and determines radiation and drug sensitivity in vivo. EMBO J. 1997, 16(6):1391–1400.
[189]Vousden KH, Prives C. Blinded by the Light: The Growing Complexity of p53. Cell, 2009,137(3):413–431
[190] Komarov PG, Komarova EA, Kondratov RV et al. A chemical inhibitor of p53 that protects mice from the side effects of cancer therapy. Science. 1999, 285(5434):1733–1737.
[191] Strom E, Sathe S, Komarov PG, et al. Small-molecule inhibitor of p53 binding to mitochondria protects mice from gamma radiation. Nat Chem Biol. 2006, 2(9):474–479.
[192] Leonova KI, Shneyder J, Antoch MP, et al. A small molecule inhibitor of p53 stimulates amplification of hematopoietic stem cells but does not promote tumor development in mice. Cell Cycle. 2010, 9(7):1434–1443.
[193]Christophorou MA, Ringshausen I, Finch AJ, et al. The pathological response to DNA damage does not contribute to p53-mediated tumour suppression. Nature, 2006, 443(7108):214–217.
[194] Komarova EA, Kondratov RV, Wang K, et al. Dual effect of p53 on radiation sensitivity in vivo: p53 promotes hematopoietic injury, but protects from gastro-intestinal syndrome in mice. Oncogene. 2004, 23(19):3265–3271.
[195]Herodin F, Bourin P, Mayol JF, et al. Short-term injection of antiapoptotic cytokine combinations soon after lethal gamma-irradiation promotes survival. Blood, 2003, 101(7):2609–2616.
[196]Karin M. Nuclear factor-kappaB in cancer development and progression. Nature, 2006, 441(7092):431–436.
[197] Burdelya LG, Krivokrysenko VI, Tallant TC, et al. An agonist of toll-like receptor 5 hasradioprotective activity in mouse and primate models. Science. 2008;320(5873):226–230.
[198] Johnson SM, Torrice CD, Bell JF, et al. Mitigation of hematologic radiation toxicity in mice through pharmacological quiescence induced by CDK4/6 inhibition. J Clin Invest. 2010, 120(7):2528–2536.
[199]Weiss J. and Landauer M. Radioprotection by antioxidants. Ann. N.Y. Acad. Sci., 2000, 899, 44–60
[200]Kumar, S. Nutritional approaches to radiation protection. Mil. Med. 2002, 167, 57–59
[201] Satyamitra M, Devi PU, Murase H, et al. In vivo radioprotection by a-TMG: preliminary studies. Mutat. Res. 2001479, 53–61
[202] Satyamitra M, Uma Devi P, Murase H, et al. In vivo postirradiation protection by a vitamin E analog, a-TMG. Radiat. Res. 2003, 160, 655–661
[203] Singh VK, Shafran RL, Jackson WE 3rd, et al. Induction of cytokines by radioprotective tocopherol analogs. Exp. Mol. Pathol. 2006, 81, 55–61
[204]Keithahn C. and Lerchl A. 5-Hydroxytryptophan is a more potent in vitro hydroxyl radical scavenger than melatonin or vitamin C. J. Pineal. Res. ,2005, 38, 62–66
[205] Vijayalaxmi, Reiter RJ, Tan DX, et al. Melatonin as a radioprotective agent: a review. Int. J. Radiat. Oncol. Biol. Phys. 2004, 59, 639–653
[206] Koc M, Taysi S, Buyukokuroglu ME, et al. Melatonin protects rat liver against irradiation-induced oxidative injury. J. Radiat. Res. 2003, 44, 211–215
[207] Vijayalaxmi, Reiter RJ, Herman TS, et al. Melatonin and radioprotection from genetic damage: in vivo/in vitro studies with human volunteers. Mutat. Res. 1996, 371, 221–228
[208]Birdsall, T.C. The biological effects and clinical uses of the pineal hormone melatonin. Alt. Med. Rev. ,1996, 1, 94–102
[209] Lusardi P, Piazza E, Fogari R. Cardiovascular effects of melatonin in hypertensive patients well controlled by nifedipine: a 24-hours study. Br. J. Clin. Pharmacol. 2000, 49, 423–427
[210]ZHONG Jinyi,SU Shim.Chin J Ind Hyg Occup Dis,1999,17(4):211-213.
[211]CHEN Jiabo,WU Weipei.J Chin Med Mater, 2004,27(9):664-665.
[212]强亦忠,王崇道,邵源.几种制剂清除辐射所致自由基的ESR研究.辐射防护,1999,19(5):371.
[213]朱丹,袁芳,孟坤,等.黄酮类化合物的研究进展.中华中医药杂志,2007,22(6):387—389.
[214] Davis TA, Clarke TK, Mog SR, et al. Subcutaneous administration of genistein prior to lethal irradiation supports multilineage, hematopoietic progenitor cell recovery and survival. Int. J. Radiat. Biol. 83, 2007, 141–151
[215] Hong H, Landauer MR, Foriska MA, et al. Antibacterial activity of the soy isoflavone genistein. J. Basic Microbiol. 2006, 46, 329–335
[216] Jagetia GC, Reddy TK. et al. The grapefruit flavonone naringin protects against the radiation-induced genomic instability in the mice bone marrow: a micronucleus study. Mutat. Res. 2002, 519, 37–48
[217] Devi PU, Bisht KS, Vinitha M. et al. A comparative study of radioprotection by Ocimum flavonoids and synthetic aminothiol protectors in the mouse. Br. J. Radiol. 1998, 71, 782–784
[218] Shimoi K, Masuda S, Furugori M, Radioprotective effect of antioxidative flavonoids in gamma-ray irradiated mice. Carcinogenesis. 1994, 15(11):2669-72.
[219] Ganasoundari A, Devi PU, Rao BS. Enhancement of bone marrow radioprotection and reduction of WR-2721 toxicity by Ocimum sanctum. Mutat. Res. 1998, 397, 303–312
[220]李卫业,李群.辐射及活性氧对DNA的损伤以及芥子碱的保护作用.植物生理学报,1997,23(4),319-323.
[221]Thiyam U,Stockmann H.Schwarz K.Antioxidant activity of rapeseed phenolics and their interactions with tocopherols during lipid oxidation I J I.Am Oil Chem Soc,2006,83:523-528.
[222]利国威,应百平.骆驼蓬碱的辐射防护作用.中华放射医学与防护杂志,1993,13(4):252-254.
[223] Gupta D,Arora R,Garg AP,et a1.Radiation-induced damage to mitochondria and its modification by podophyllum hexandmm Royale in HepG2 cells.Mol Cell Bioehem,2003,247(3):25.
[224] Gupta D. AroraR,GargAP,et a1.Modification of radiation-damage to mitochondrial system in vivo by Pod ophylhm hexandrum:mechanistic aspects.Mol Cell Biochem,2004,266(1-2):65.
[225] Sajikumar S. God HC.Podophylam hexandmm prevents radiation induced neuronal damage in post-natal rats exposed in utero.Phytother Res,2003,17(7):761.
[226] God Hc.Salin CA,Prakash H.Protection of jejunal crypts by RH-3 (a preparation of Hippophae rhamnoides) against lethal whole body gamma irradiation.Phytother Res,2003,17(3):222.
[227] Prem KI,Samanta N. Goel HC.Modulation of chromatin organization by RH-3,a preparation of Hippophae rhamnoides,a possible role in radioprotection.MoI CelI Biochem,2002,238(1-2):1.
[228] Arora R,Sharma RK.Prasad J.et a1.Radioprotective efficacy of Hippophae rhamnoides.In Proceedings of the Seminar on Sea Buckthorn:A Resource for Environment.Health and Economy,2004,31 (2):21.
[229] Arora R,Gupta D.Garg AP.et a1.Radioprotection of mice liver mitochondria by Hippophae rhamnoides L.in rive.In Proceedings of 3rd Biennial Conference on Hyperthermic Oncology and Medicine.Pharmacol Ther,2003,39(2):347.
[230] God HC,Prem KI,Samanta N,et a1.Induction of DNA-protein cross-links by Hippophae rhanmoides,implications in radioprotection and cytotoxicity.Mol Cell Biochem,2003.245(1-2):57.
[231] GuptaD.AtomR,GuptaS,et a1.Radiation-induced oxidative damage to mitochondria and its modification by endogenous antioxidants in vivo:role of some herbal preparations.Indian J Nuclear Med,2003,18(3):14.
[232]Amra R,Gupta D.Sharma AK,et a1.Modification of radiation-induced damage in mammalian model systems by natural plant products:implications for radiation protection In Proceedings of the IUPAC.International Conference on Biodiversity and Natural Products,2004,33(4):56.
[233] Weiss JF, Landauer MR.Protection against ionizing radiation by antioxidant nutrients and phytochemicals.Toxicology,2003.1 89(1-2):1.
[234] Samarth RM, Kumar A.Mentha piperita(Linn )leaf extract provides protection against radiation induced chromosomal damage in bone marrow of mice.Indian J Exp Biol,2003,41(3):229.
[235] God HC,Prasad J,Singh S, et a1.Radioprotective potential of a herbal extract of Tinospora cordifolia.J Radiat Res,2004,45(1):61.
[236] Pahadiya S,Sharma J.Alteration of lethal efects of gamma rays in Swiss albino mice byTinospom cordifolia.Phytother Res,2003,17 (5):552.
[237]黄绵庆,阎春玲,窦梅,等.扇贝多肽对UVB损伤HaCat细胞的抗氧化作用.中国海洋药物. 2005 ;24 (3)26.
[238] Karsten Stahnke, Simone Fulda, Claudia Friesen, et al.Activation of apoptosis pathways in peripheral blood lymphocytes by in vivo chemotherapy. Blood, Nov 2001, 98: 3066 - 3073.
[239]吕丽爽.天然抗氧化剂低聚原花青素的研究进展.食品科技,2000,23(2):147-150
[240]董海东,陈静,陈慰峰.胸腺树突状细胞对胸腺细胞凋亡的促进作用.中国科学(C辑),1997,27(6):550-554.
[241]崔玉芳,高亚兵等,小鼠胸腺淋巴细胞辐射损伤特点和机理的研究。中国体视学与图像分析,1998;12(3):208-213.
[242] Green, D. R., Kroemer, G. (2004) The pathophysiology of mitochondrial cell death. Science 305, 626-629.
[243] Thorburn, A. (2004) Death receptor-induced cell killing. Cell Signal. 16, 139-144.
[244] Alvarez S, DranéP, Meiller A, et al. A comprehensive study of p53 transcriptional activity in thymus and spleen of gamma irradiated mouse: high sensitivity of genes involved in the two main apoptotic pathways. Int J Radiat Biol. 2006 , 82(11):761-70.
[245] Kang YH, Lee SJ. Role of p38 MAPK and JNK in enhanced cervical cancer cell killing by the combination of arsenic trioxide and ionizing radiation. Oncol Rep. 2008 , 20(3):637-43.
[246] Narang H, Krishna M. Effect of nitric oxide donor and gamma irradiation on MAPK signaling in murine peritoneal macrophages. J Cell Biochem. 2008 1;103(2):576-87.
[247] Ide T. Mechanism of cell proliferation--cell cycle, oncogenes, and senescence Yakugaku Zasshi. 2006, 126(11):1087~1115.
[248] Samuel T, Weber HO, Funk JO, et al. Linking DNA damage to cell cycle checkpoints. Cell Cycle. 2002, 162-168.
[249]刘扬,金光辉,刘树铮。流式细胞术在紫外线照射后细胞内活性氧检测中的应用。吉林大学学报,2004, 30(6): 975~977
[250] Singh RP, Dhanalakshmi S, Mohan S, et al. Silibinin inhibits UVB and epidermal growth factor-induced mitogenic and cell survival signaling involving activator protein-1 and nuclear factor-kappaB in mouse epidermal JB6 cells. Mol Cancer Ther. 2006, 5 (5): 1145~1153.
[251] Afaq F, Syed DN, Malik A, et al. Delphinidin, an anthocyanidin in pigmented fruits andvegetables, protects human HaCaT keratinocytes and mouse skin against UVB-mediated oxidative stress and apoptosis. J Invest Dermatol. 2007, 127 (1): 222~232.
[252]王崇道,强亦忠.中华放射医学与防护杂志,2002,22(6):461-463
[253] Svobodova A, Walterova D, Vostalova J. Ultraviolet light induced alteration to the skin. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2006, 150 (1): 25~38.
[254] Bras M, Queenan B, Susin SA. 2005. Programmed cell death via mitochondria: Different modes of dying. Biochemistry Biokhimiia 70:231–239.
[255] Klener P Jr, Andera L, Klener P, Necas E, Zivny′J. 2006. Cell death signalling pathways in the pathogenesis and therapy of haematologic malignancies: Overview of apoptotic pathways. Folia Biologica 52:34–44.
[256] Chen M, Wang J. Initiator caspases in apoptosis signaling pathways. Apoptosis,2002, 7, 313-319.
[257] Yang J, Liu X, Bhalla K, et al. Prevention of apoptosis by Bcl-2: release of cytochrome c from mitochondria blocked. Science,1997,275, 1129-1132.
[258] Zhu XF,Zhang XS,Li ZM,et al.Apoptosis induced by ceramide in hepatocellelar carcinoma Bel7402 cells.Acta Pharmacol Sin,2000,21:225～228
[259] Harris MH, Thompson CB. The role of the Bcl-2 family in the regulation of outer mitochondrial membrane permeability. Cell Death Differ, 2000, 7(12):1182-1191.
[260] Kuwana T, Mackey MR, Perkins G. Bid, Bax and lipids cooperate to form supramolecular openings in the outer mitochondrial membrane.Cell, 2002, 111(3):331-342.
[261] Wu Y, Xing D, Chen WR. Single cell FRET imaging for determination of pathway of tumor cell apoptosis induced by photofrin-PDT, Cell Cycle, 2006, 5:729-734.
[262] Hengartner MO, Horvitz HR. C. elegans cell survival gene ced-9 encodes a functional homolog of the mammalian proto-oncogene bcl-2. Cell. 1994, 25;76(4):665-76.
[263] Hochman A, Sternin H, Gorodin S, et al. Enhanced oxidative stress and altered antioxidants in brains of Bcl-2-deficient mice. J Neurochem. 1998, 71(2):741-8.
[264] Kulms D, Zeise E, P?ppelmann B, et al. DNA damage, death receptor activation and reactive oxygen species contribute to ultraviolet radiation-induced apoptosis in an essential and independent way. Oncogene. 2002 ,29;21(38):5844-51.
[265] Chinnaiyan et al., 1996; Kischkel et al., 2001; Seol et al., 2001; Kang et al., 2003
[266] Snopov SA, de Gruijl FR, Roza L, et al. Immunochemical study of DNA modifications in the nuclei of UV-damaged lymphocytes. Photochem. Photobiol. Sci 2004, 3: 85~90.
[267] Staniforth V, Chiu LT, Yang NS. Caffeic acid suppresses UVB radiation-induced expression of interleukin-10 and activation of mitogen-activated protein kinases in mouse. Carcinogenesis. 2006, 27 (9): 1803~1811.
[268] VAN LAETHEM A, NYS K, VAN KELST S, et al. Apoptosis signal regulating kinase1 connects reactive oxygen species to p38 MAPKinduced mitochondrial apoptosis in UVBirradiated human keratinocytes. Free Radic Biol Med, 2006,41(9):1361.
[269]于爽,郭沈波,严州萍,等.扇贝多肽对UVB损伤HaCa T细胞ERKs/MAPKs通路的影响.齐鲁医学杂志, 2006, 21(3):189-192.
[270] Yin Z M, Sima J, WU Y F, et al. The effect of C-terminal fragment of JNK2 on the stability of p53 and cell proliferation. Cell Res, 2004, 14(5): 434~438
[271] Martindale J L, Holbrook N J. Cellular response to oxidative stress: signaling for suicide and survival. J Cell Physiol, 2002, 192(1): 1~15
[272] Kennedy NJ, Cellurale C, Davis RJ. A radical role for p38 MAPK in tumor initiation. Cancer Cell 2007, 11: 101-103.
[273] Kharbanda S, Saxena S, Yoshida K, et al. Translocation of SAPK/JNK to mitochondria and interaction with Bcl-x(L) in response to DNA damage. J Biol Chem, 2000, 275(1): 322~327
[274] Lei K, Davis R J. JNK phosphorylation of Bim-related members of the Bcl2 family induces Bax-dependent apoptosis. Proc Natl Acad Sci USA, 2003, 100(5): 2432~2437
[275] Matsui Y, Tsuchida Y, Keng PC. Effects of p53 mutations on cellular sensitivity to ionizing radiation. Am J Clin Oncol. 2001, 24(5) 486-490.
[276] Bassett EA, Wang W, Rastinejad F, et al. Structural and functional basis for therapeutic modulation of p53 signaling. Clin Cancer Res. 2008, 15, 14(20):6376-86.
[277] Trinei M, Giorgio M, Cicalese A, et al. A p53-p66Shc signalling pathway controls intracellular redox status, levels of oxidation-damaged DNA and oxidative stress-induced apoptosis. Oncogene. 2002, 30;21(24):3872-8.
[278] Flatt PM, Price JO, Shaw A, et al. Differential cell cycle checkpoint response in normal human keratinocytes and fibroblasts. Cell Growth Differ. 1998, 9(7):535-43.
[279] Taylor WR,Stark GR.Regulation of the G2/M transition by p53.Oncogene,2001,20(15):1803～1815.
[280] Foijer F, te Riele H. Check, double check: the G2 barrier to cancer. Cell Cycle. 2006, 5(8):831-6.
[2]Oh YT, Kim CH, Choi JH, et al. Sensory neural hearing loss after concurrent cisplatin and radiation therapy for nasopharyngeal carcinoma. Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology, 2004, 72:79–82.
[3]Sonis ST, Elting LS, Keefe D, et al. Perspectives on cancer therapy-induced mucosal injury: Pathogenesis, measurement, epidemiology, and consequences for patients. Cancer, 2004,100: 1995–2025.
[4]雷筱芬,陈木森.黄酮类化合物抗辐射研究进展.江西农业大学学报,2007,29(6):1039-1042.
[5]段伟,毕良文,秦继勇,等.辐射防护药物研究进展.中国辐射卫生,2006,15(1):l14-115.
[6]王岳飞,唐德松,朴宰日,等.茶多酚对荷瘤小鼠辐射损伤的影响.中华放射医学与防护杂志,2004,24(3):263.
[7]吕秋军,温利青,张敏,等.白藜芦醇的辐射防护及其分子机理的研究.中华放射医学与防护杂志,2004,24(1):21.
[8]孙维琦,郭英,张义全,等.大豆异黄酮与大豆皂甙抗辐射作用的实验研究.中国辐射卫生,2007,16(3):273-274.
[9]李德远,周韫珍,余应利,等.银杏叶黄酮抗辐射效应研究.营养学报,2004,26(3):220-222.
[10]Goda Y, Shimizu T, Kato Y, et al. Two acylated anthocyanins from purple sweet potato. Phytochemistry, 1997,44(1):183~186
[11] Terahara N, Konczak Islam I, Nakatani M, et al. Anthocyanins in callus induced from purple storage root of Ipomoea batatas L. Phytochemistry, 2000,54(8):919~922
[12]陈勇,张晴.AB-8大孔吸附树脂吸附和分离甘薯紫色素的研究.中国食品添加剂, 2001,(1):6~9
[13]沈勇根,上官新晨,徐明生,等.紫红薯色素的提取和精制.江西农业大学学报.2004,26(6):912~916
[14]Islam MS, Yoshimoto M, Terahara N, et al. Anthocyanin compositions in sweetpotato(Ipomoea batatas L.) leaves. Bioscience, Biotechnology, and Biochemistry,2002,66:2483–2486.
[15]Terahara N, Konczak I, Ono H, et al. Characterization of acylated anthocyanins in callus induced from storage root of purple-fleshed sweet potato, Ipomoea batatas L. Journal of Biomedicine & Biotechnology, 2004,2004:279–286.
[16]Suda I, Oki T, Masuda M, et al. Direct absorption of acylated anthocyanin in purple-fleshed sweet potato into rats. Journal of Agriculture and Food Chemistry. 2002,50(6):1672~1676
[17]姜平平,吕晓玲.紫心甘薯花色苷抗氧化活性体外实验研究.中国食品添加剂,2002,(6):8~11
[18]吕晓玲,孙晓侠,姚秀玲.采用荧光化学发光法分析紫甘薯花色苷产品的抗氧化作用.食品与发酵工业, 2005,31(9):53~55
[19]Kano M, Takayanagi T, Harada K, et al. Antioxidative activity of anthocyanins from purple sweet potato, Ipomoera batatas cultivar Ayamurasaki. Bioscience, Biotechnology, and Biochemistry, 2005,69:979–988.
[20]Yoshimoto M, Okuno S, Yamaguchi M, et al. Antimutagenicity of decylated anthocyanins in purple-fleshed sweet potato. Bioscience-Biotechnology And Biochemistry. 2001, 65(7):1652~1655
[21]Brown DQ, Pittock JW 3rd, Rubinstein JS. Early results of the screening program for radioprotectors. Int. J. Radiat. Oncol. Biol. Phys., 1982, 8, 565–570
[22] Cassatt DR, Fazenbaker CA, Bachy CM, et al. Preclinical modeling of improved amifostine (ethyol) use in radiation therapy. Semin. Radiat. Oncol. 2002, 12, 97–102
[23] Koukourakis MI, Kyrias G, Kakolyris S, et al. Subcutaneous administration of amifostine during fractionated radiotherapy: a randomized phase II study. J. Clin. Oncol. 2000,18, 2226–2233
[24] Whitnall MH, Elliott TB, Harding RA, et al. Androstenediol stimulates myelopoiesis and enhances resistance to infection in gamma-irradiated mice. Int. J. Immunopharmacol. 2000, 22, 1–14
[25] Landauer MR, Srinivasan V, Seed TM, et al. Genistein treatment protects mice from ionizing radiation injury. J. Appl. Toxicol. 2003, 23, 379–385
[26]Karbownik, M. and Reiter, R.J. Antioxidative effects of melatonin in protection against cellular damage caused by ionizing radiation. Exp. Biol. Med. 2000, 225: 9–22
[27]Nair CKK, Parida DK, Nomura T. Radioprotectors in Radiotherapy. J Radiat Res 2001;42 :21–37.
[28]Gopal R, Tucker SL, Komaki R, et al. The relationship between local dose and loss of function for irradiation lung. I J R O B P, 2003, 56(1):106-113.
[29]Marks LB. Dosimetric predictors of radiation-induced lung injury. I JROBP 2002, 54(2):313–316.
[30]Brown JM, Wilson WR. Exploiting tumour hypoxia in cancer treatment. Nat Rev Cancer 2004,4:437–447.
[31]Le Q-T. Identifying and targeting hypoxia in head and neck cancer: A brief overview of current approaches. Int J Radiation Oncology Biol Phys 2007, 69(2 Supplement):S56–S58.
[32]Bayir H, Fadeel B, Palladino MJ, et al. Apoptotic interactions of cytochrome c: Redox flirting with anionic phospholipids within and outside of mitochondria. Biochimica et Biophysica Acta 2006,1757:648–659.
[33]Kagan VE, Tyrina YY, Bayir H, et al. The“pro-apoptotic genies”get out of mitochondria: Oxidative lipidomics and redox activity of cytochrome c/cardiolipin complexes. Chem Biol Interact 2006,163:15–28.
[34]Anscher MS, Kong FM, Andrews K, et al. Plasma TFG,1 as a predictor of radiation pneumonitis. I JROBP 1998,41:1029–1035.
[35]Rubin P, Johnston CJ, Williams JP, et al. A perpetual cascade of cytokines postirradiation leads to pulmonary fibrosis. Int J Radiat Oncol Bio Phys 1995, 33:99–109.
[36]Mendonca MS, Mayhugh BM, McDowell B, et al. A radiation-induced acute apoptosis involving TP53 and BAX precedes the delayed apoptosis and neoplastic transformation of CGL1 human hybrid cells. Rad Res, 2005,163:614–622.
[37]Maiuri MC, Zalckvar E, Kimchi A, et al. Self-eating and self-killing: crosstalk between autophagy and apoptosis. Nature Reviews: Mol Cell Bio, 2007, 8:741–748.
[38]Niu Y, Epperly MW, Shen H, et al. Intraesophageal MnSOD-plasmid liposome administration enhances engraftment and self-renewal capacity of bone marrow derived progenitors of esophageal squamous epithelium. Gene Therapy, 2008, 15:347–356.
[39]Li X-M, Hu Z, Jorgenson ML, et al. Bone marrow sinusoidal endothelial cells undergo nonapoptotic cell death and are replaced by proliferating sinusoidal cells in situ to maintain thevascular niche following lethal irradiation. Exper Hematol, 2008, 36:1143–1156.
[40]Ricardo SD, van Goor H, HedíAA. Macrophage diversity in renal injury and repair. J Clin Inves, 2008,118:3522–3529.
[41]Belkacemi Y, Labopin M, Hennequin C, et al. Reduced-intensity conditioning regimen using low-dose total body irradiation before allogeneic transplant for hematologic malignancies: Experience from the European group for blood and marrow transplantation. Int J Rad Oncol Biol Phys, 2007, 67:544–551.
[42]Wong JYC, Liu A, Schultheiss T, et al. Targeted total marrow irradiation using three-dimensional image-guided tomographic intensitymodulated radiation therapy: An alternative to standard total body irradiation. Biol Blood Marrow Transplant, 2006,12:306–315.
[43]Sorror ML, Storer BE, Maloney DG, et al. Outcomes after allogeneic hematopoietic cell transplantation with nonmyeloablative conditioning regimens for treatment of lymphoma and chronic lymphocytic leukemia. Blood, 2008, 111:446–452.
[44]Rotblat J, Lindop P. Long-term effects of a single whole-body exposure of mice to ionizing radiations. II. Causes of death. Proc R Soc Lond, 1961, 154:350–368.
[45]Haupt R, Fears TR, Robison LL, et al. Educational attainment in long-term survivors of childhood acute lymphoblastic leukemia. JAMA, 1994, 272:1427–1432.
[46]Van Dongen-Melman JEWM, De Groot A, Van Dongen JJM, et al. Cranial irradiation is the major cause of learning problems in children treated for leukemia and lymphoma: A comparative study. Leukemia, 1997, 11:1197–1200.
[47]Laack NN, Brown PD, Ivnik RJ, et al. Cognitive function after radiotherapy for supratentorial low-grade glioma: A north central cancer treatment group prospective study. Int J Rad Oncol Biol Phys, 2005,63(4):1175–1183.
[48]Zhou S, Greenberger JS, Epperly MW, et al. Age-related intrinsic changes in human bone marrow-derived mesenchymal stem cells and their differentiation to osteoblasts. Aging Cell, 2008, 7:335–343.
[49]Epperly MW, Dixon T, Wang H, et al. Modulation of radiation-induced life shortening by systemic intravenous MnSOD-plasmid liposome gene therapy. Rad Res, 2008, 170:437–443.
[50]Little, J.B. Radiation carcinogenesis. Carcinogenesis, 2000, 21, 397–404
[51]Muramoto GG, Chen B, Cui X, et al. Vascular endothelial cells produce soluble factors that mediate the recovery of human hematopoietic stem cells after radiation injury. Biol Blood Marrow Transplant, 2006,12:530–540.
[52]Chute JP, Muramoto GG, Salter AB, et al. Transplantation of vascular endothelial cells mediates the hematopoietic recovery and survival of lethally irradiated mice. Blood, 2007, 109:2365–2372.
[53]Dai Y, Grant S. Targeting multiple arms of the apoptotic regulatory machinery. Cancer Res, 2007,67:2908–2911.
[54]Gardai SJ, Bratton DL, Ogden CA, et al. Recognition ligands on apoptotic cells: a perspective. J Leukoc Bio, 2006,79:896–903.
[55]Seed TM, Kaspar LV. Probing altered hematopoietic progenitor cells of preleukemic dogs with JANUS fission neutrons. Rad Res, 1991,128:S81–S86.
[56]Seed TM, Kaspar LV, Grdina DJ. Hematopoietic repair modifications during preclinical phases of chronic radiation-induced myeloproliferative disease. Exp Hematol ,1986,14 :433.
[57]Seed TM, Kaspar LV. Changing patterns of radiosensitivity of hematopoietic progenitors from chronically irradiated dogs prone either to aplastic anemia or to myeloproliferative disease. Leukemia Res ,1990,14:299–307.
[58]Seed TM, Kaspar LV, Tolle DV, et al. Chronic radiation leukemogenesis : Postnatal hematopathologic effects resulting from in-utero irradiation. Leukemia Res, 1987,11 :171–179.
[59]Seed TM, Carnes BA, Tolle DV, et al. Blood responses under chronic low daily dose gamma irradiation: I. Differential preclinical responses of irradiated male dogs in progression to either aplastic anemia or myeloproliferative disease. Leukemia Res, 1989,13 :1069–1084.
[60]Kang SK, Rabbani ZN, Folz RJ, et al. Overexpression of extracellular superoxide dismutase protects mice from radiation-induced lung injury. I J R O B P , 2003, 57:1056–1066.
[61]Greenberger, JS.; Epperly, MW. Pleiotrophic stem cell and tissue effects of ionizing irradiation protection by MnSOD-plasmid liposome gene therapy. In: Redberry, GW., editor. Gene Therapy in Cancer. Nova Science Publishers, Inc; 2005. p. 191-215.
[62]Gorbunov NV, Poque-Geile KL, Epperly MW, et al. Activation of the nitric oxide synthase 2 pathway in the response of bone marrow stromal cells to high doses of ionizing radiation. Rad Res, 2000,154:73–86.
[63]Constine LS, Tarbell N, Hudson MM, et al. Subsequent malignancies in children treated for Hodgkin’s disease: Associations with gender and radiation dose. Int J Rad Onc Biol Phys, 2008, 72:24–33.
[64]Romanik EA, Leif J, Sakakeeny MA, et al. Sequence analysis of mutational hot spots in the endogenous and transfected CSF-1 receptor in gamma-irradiation induced factor-independent subclones of clonal hematopoietic progenitor cell lines. Radiat Oncol Invest: Clin Bas Res ,1993, 1:94–102.
[65]Wang J, Zheng H, Ou X, et al. Deficiency of microvascular thrombomodulin and upregulation of protease-activated receptor-1 in irradiated rat intestine. Possible link between endothelial dysfunction and chronic radiation fibrosis. Am J Pathol , 2002,160:2063–2070.
[66]Flanders KC, Sullivan CD, Fujii M, et al. Mice lacking Smad3 are protected against cutaneous injury induced by ionizing radiation. Am J Pathol, 2002, 160:1057–1068.
[67]Anzano MA, Mitchell JB, Russo A, et al. Interference with transforming growth factor-beta/Smad3 signaling results in accelerated healing of wounds in previously irradiated skin. Am J Pathol ,2003, 163:2247–2257.
[68]Dileto CL, Travis EL. Fibroblast radiosensitivity in vitro and lung fibrosis in vivo: Comparison between a fibrosis-prone and fibrosis-resistant mouse strain. Rad Res, 1996,146:61–67.
[69]Kanai A, Epperly M, Pearce L, et al. Differing roles of mitochondrial nitric oxide synthase in cardiomyocytes and urothelial cells. Am J Physiol Heart Circ Physiol, 2004,286:H13–H21.
[70]Safwat A, Bentzen SM, Turesson I, et al. Deterministic rather than stochastic factors explain most of the variation in the expression of skin telangiectasia after radiotherapy. Int J Radiat Oncol Biol Phys, 2002, 52:198–204.
[71]Moulder JE, Cohen EP. Future strategies for mitigation and treatment of chronic radiation-induced normal tissue injury. Semin Rad Onco, 2007, 17:141–148.
[72]Moulder JE, Fish BL, Cohen EP. Treatment of radiation nephropathy with ACE inhibitors and AII type-1 and type-2 receptor antagonists. Current Pharm Design, 2007, 13 :1317–1325.
[73]Cohen EP, Irving AA, Drobyski WR, et al. Captopril to mitigate chronic renal failure after hematopoietic stem cell transplantation: a randomized controlled trial. Int J Rad Oncol Biol Phys, 2008, 70:1546–1551.
[74]Mothersill C, Seymour C. Radiation-induced bystander effects: Past history and future directions. Rad Res, 2001, 155:759–767.
[75]Stone HB, Moulder JE, Coleman CN, et al. Models for evaluating agents intended for the prophylaxis, mitigation, and treatment of radiation injuries. Rad Res , 2004, 162:711–718.
[76] Hosseinimehr SJ, Zakaryaee V, Froughizadeh M, et al. Oral oxymetholone reduces mortality induced by gamma irradiation in mice through stimulation of hematopoietic cells. Mol. Cell. Biochem. 2006, 287, 193–199
[77]Zhou, Y. and Mi, M.T. Genistein stimulates hematopoiesis and increases survival in irradiated mice. J. Radiat. Res. 2005, 46, 425–433
[78]Dainiak, N. Hematologic consequences of exposure to ionizing radiation. Exp. Hematol. 2002, 30, 513–528
[79]Qiu Wei C-W, Carson-Walter EB, Liu H, et al. PUMA regulates intestinal progenitor cell radiosensitivity and gastrointestinal syndrome. Cell, Stem Cell , 2008, 2:576–583.
[80]Morgan JL, Holcomb TM, Morrissey RW. Radiation reaction in ataxia telangiectasia. Am J Dis Child ,1968, 116:557–558.
[81] Ho AY, Atencio DP, Peters S, et al. Genetic predictors of adverse radiotherapy effects: The Gene-PARE project. Int J Radiat Oncol Biol Phys, 2006, 65:646–655.
[82]Shiloh Y. ATM and related protein kinases: Safeguarding genome integrity. Nat Rev Cancer, 2003, 3:155–168.
[83]Abraham RT. Cell cycle checkpoint signaling through the ATM and ATR kinases. Genes Dev, 2001, 15:2177–2196.
[84]Casado JA, Nunez MI, Segovia JC, et al. Non-homologous end-joining defect in fanconi anemia hematopoietic cells exposed to ionizing radiation. Rad Res , 2005, 164:635–641.
[85] Taniguchi T, Garcia-Hiquera I, Xu B, et al. Convergence of the fanconi anemia and ataxia telangiectasia signaling pathways. Cell ,2002, 109:459–472.
[86]Marcou Y, D’Andrea A, Jeggo PA, et al. Normal cellular radiosensitivity in an adult Fanconi anemia patient with marked clinical radiosensitivity. Radiother Oncol, 2001, 60 :75–79.
[87]Imamura O, Fujita K, Itoh C, et al. Werner and Bloom helicases are involved in DNA repair in a complementary fashion. Oncogene, 2002, 21 :954–963.
[88]Imamura O, Campbell JL. The human Bloom syndrome gene suppresses the DNA replicationand repair defects of yeast dna2 mutants. Proc Natl Acad Sci USA ,2003,100:8193–8198.
[89]Maisin, J.R. Bacq and Alexander award lecture chemical radioprotection: past, present and future prospects. Int. J. Radiat. Biol. 1998, 73, 443–450
[90]Greenberger JS, Epperly MW, Gretton J, et al. Radioprotective gene therapy. Curr Gene Ther 2003;3:183–195.
[91]Greenberger JS, Epperly MW. Radioprotective antioxidant gene therapy: Potential mechanisms of action. Gene Ther Mol Biol, 2004, 8:31–44.
[92]Gandhi NM, Nair CKK. Radiation protection by diethyldithiocarbamate: protection of membrane and DNA in vitro and in vivo againstγ-irradiation. J. Radiat. Res, 2004, 45:175–180.
[93]Yuhas JM, Davis ME, Glover D, et al. Circumvention of the tumor membrane barrier to WR-2721 absorption by reduction of the drug hydrophilicity. Int. J. Radiat. Oncol, 1982, 8:519–522.
[94]Anscher MS, Chen L, Rabbani Z, et al. Recent progress in defining mechanisms and potential targets for prevention of normal tissue injury after radiation therapy. Int. J. Radiat. Oncol. Biol. Phys, 2005, 62:255–259.
[95]Epperly MW, Bray J, Kraeger S, et al. Prevention of late effects of irradiation lung damage by manganese superoxide dismutase gene therapy. Gene Ther, 1998, 5:196–208.
[96]Vujaskovic Z, Batinic-Haberle I, Rabbani ZN, et al. A small molecule weight catalytic metalloporphyrin antioxidant with superoxide dismutase (SOD) mimetic properties protects lungs from radiation-induced injury. Free Rad. Biol. Med, 2002, 33:857–863.
[97]Lefaix J-L, Delanian S, Leplat J-J, et al. Successful treatment of radiation-induced fibrosis using Cu/Zn-SOD and Mn-SOD: an experimental study. Int. J. Radiat. Oncol. Biol. Phys, 1996, 35:305–312.
[98]Lin Z, Nei M, Ma H. The origins and early evolution of DNA mismatch repair genes-multiple horizontal gene transfers and co-evolution. Nucleic Acids Res, 2007, 35:7591–7603.
[99]Bennett CB, Lewis LK, Karthikeyan G, et al. Genes required for ionizing radiation resistance in yeast. Nat Genet, 2001, 29 :426–434
[100]Cox MC, Battista JR. Deinococcus radiodurans the consummate survivor. Nature Reviews: Micro, 2005, 3:882–892.
[101]Daly MJ, Gaidamakova EK, Matrosova VY, et al. Accumulation of Mn(II) in deinococcus radiodurans facilitates gamma-radiation resistance. Science, 2004, 306:1025–1030.
[102]Zheng S, Newton GL, Ward JF, et al. Aerobic radioprotection of pBR322 by thiols: effect of thiol net charge upon scavenging of hydroxyl radicals and repair of DNA radicals. Radiat. Res, 1992, 130:183–193.
[103]Kumar SS, Devasagayam TPA, Jayshree B, et al. Mechanism of protection against radiation-induced DNA damage in plasmid pBR322 by caffeine. Int. J. Radiat. Biol, 2001, 77:617–623.
[104]Reiter RJ, Tan D, Mayo JC, et al. Melatonin as an antioxidant: biochemical mechanisms and pathophysiological implications in humans. Acta. Biochem. Pol, 2003, 50:1129–1146.
[105]Maurya DK, Salvi VP, Nair CKK. Radioprotection of normal tissues in tumor-bearing mice by troxerutin. J. Radiat. Res, 2004, 45:221–228.
[106]Uma Devi P, Bisht KS, Vinitha M. A comparative study of radioprotection by Ocimum flavonoids and synthetic animothiol protectors in the mouse. Brit. J. Radiol, 1998, 71:782–784.
[107]Weiss JF, Landauer MR. Protection against ionizing radiation by antioxidant nutrients and phytochemicals. Toxicology ,2003,189:1–20.
[108]Frei B, Higdon JV. Antioxidant activity of tea polyphenols in vivo: evidence from animal studies. J. Nutr, 2003, 133:3275S–3284S.
[109]Murley JS, Kataoka Y, Cao D, et al. Delayed radioprotection by NFκB-mediated induction of SOD2 (MnSOD) in SA-NH tumor cells after exposure to clinically used thiol-containing drugs. Radiat. Res, 2004, 162:536–546.
[110]Murley JS, Kataoka Y, Weydert CJ, et al. Delayed radioprotection by nuclear transcription factorκB-mediated induction of manganese superoxide dismutase in human microvascular endothelial cells after exposure to the free radical scavenger, WR1065. Free Rad. Biol. Med, 2006, 40:1004–1016.
[111]Wispe JR, Warner BB, Clark JC, et al. Human MnSOD in pulmonary epithelial cells of transgenic mice confers protection from oxygen injury. J Biol Chem, 1992, 267:23937–23941.
[112]Zhang X, Epperly MW, Kay MA, et al. Radioprotection in vitro and in vivo by minicircle plasmid carrying the human manganese superoxide dismutase transgene. Hum Gene Ther ,2008,19:820–826.
[113]Gauter-Fleckenstein B, Fleckenstein K, Owzar K, et al. Comparison of two Mn porphyrin-based mimics of superoxide dismutase in pulmonary radioprotection. Free Radic Biol Med, 2007, 44:982–989.
[114]Carpenter M, Epperly MW, Agarwal A, et al. Inhalation delivery of manganese superoxide dismutase-plasmid/liposomes (MnSOD-PL) protects the murine lung from irradiation damage. Gene Ther, 2005, 12:685–690.
[115]McClain DE, Kalinich JF, Ramakrishnan N. Trolox inhibits apoptosis in irradiated MOLT-4 lymphocytes. FASEB, 1995, 9:1345–1354.
[116]Fink M, Macias CA, Xiao J, et al. Hemigramicidin-TEMPO conjugates: Novel mitochondria-targeted antioxidants. Crit Care Med ,2007, 35:5461–5470
[117]Jiang J, Belikova NA, Hoye AT, et al. A mitochondria-targeted nitroxide/hemi-gramicidin S conjugate protects mouse embryonic cells againstγ-irradiation. I J R O B P ,2008,70:816–825.
[118]Amstad P, Peskin A, Shah G, et al. The balance between Cu, Zn-superoxide dismutase and catalase affects the sensitivity of mouse epidermal cells to oxidative stress. Biochemistry ,1991, 30:9305–9313.
[119]Rix-Montel MA. Biophysical aspects of radioprotectors by aminothiols. Engineering in Medicine and Biology Society, 1988, 2:1032–1033.
[120]Murley JS, Kataoka Y, Weydert CJ, et al. Delayed radioprotection by nuclear transcription factor kB-mediated induction of manganese superoxide dismutase in human microvascular endothelial cells after exposure to free radical scavenger WR1065. Free Radical Biol Med, 2006,40:1004–1016.
[121] Herceg Z, Milosvic Z, Kljajic R, et al. The effects of use of radioprotective compound WR-2721 on haematological parameters in lethally irradiated swines. YRPA, Proceedings of the 3rd Italian-Yugoslav Symposium on Radiation Protection; Plitvice, Yugloslavia. 1990. 30-35.
[122]Salganik RI. The benefits and hazards of antioxidants: controlling apoptosis and other protective mechanisms in cancer patients and the human population. J. Am. Coll. Nutr ,2001,20:464S–472S.
[123]Hernández-Flores G, Gómez-Contreras PC, Domínguez-Rodríguez JR, et al.γ-irradiationinduced apoptosis in peritoneal macrophages by oxidative stress. Implications of antioxidants in caspase mitochondrial pathway. Anticancer Res, 2005, 25:4091–4100.
[124]Kondo H, Park S-H, Watanabe K, et al. Polyphenol (?)-epigallocatechin gallate inhibits apoptosis induced by irradiation in human HaCaT keratinocytes. Biochem. Biophys. Res. Commun, 2004,316:59–64.
[125]Khodarev NN, Kataoka Y, Murley JS, et al. Interaction of amifostine and ionizing radiation on transcriptional patterns of apoptotic genes expressed in human microvascular endothelial cells (HMEC). Int. J. Radiat. Oncol. Biol. Phys, 2004, 60:553–563.
[126] Drouet M, Mourcin F, Grenier N, et al. Single administration of stem cell factor, FLT-3 ligand, megakaryocyte growth and development factor, and interleukin-3 in combination soon after irradiation prevents nonhuman primates from myelosuppression: longterm follow-up of hematopoiesis. Blood, 2004, 103, 878–885
[127] Hérodin F, Bourin P, Mayol JF, et al. Short-term injection of antiapoptotic cytokine combinations soon after lethal g-irradiation promotes survival. Blood, 2003, 101, 2609–2616
[128] Whitnall MH, Wilhelmsen CL, McKinney L, et al. Radioprotective efficacy and acute toxicity of 5-androstenediol after subcutaneous or oral administration in mice. Immunopharm. Immunotoxicol. 2002, 24, 595–626
[129]Rowinsky EK. Targeted induction of apoptosis in cancer management: The emerging role of tumor necrosis factor-related apoptosis-inducing ligand receptor activating agents. J Clin Oncol, 2005, 23:9394–9407.
[130]Grdina DJ, Murley JS, Kataoka Y, et al. Differential activation of nuclear transcription factor KB, gene expression, and proteins by amifostine’s free thiol in human microvascular endothelial and glioma cells. Semin Radiat Oncol, 2002,12:103–111.
[131]Baumann M, Krause M, Hill R. Exploring the role of cancer stem cells in radioresistance. Nature Reviews Cancer, 2008, 8:545–552.
[132]Held KD. and Biaglow, J. (1994) Mechanisms for the oxygen radical-mediated toxicity of various thiol-containing compounds in cultured mammalian cells. Radiat. Res. 139, 15–23
[133] Weiss JF, Kumar KS, Walden TL, et al. Advances in radioprotection through the use of combined agent regimens. Int. J. Radiat. Biol. 1990, 57, 709–722
[134]Holland J. New treatment modulation in radiation therapy. J. Infus. Nurs. , 2001,24, 95–101
[135]Mazur L. Radioprotective effects of the thiols GSH and WR-2721 against Xrays-induction of micronuclei in erythroblasts. Mutat. Res., 2000, 468, 27–33
[136]Spencer CM. and Goa, K.L. Amifostine, a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential as a radioprotector and cytotoxic chemoprotector. Drugs,1995, 50, 1001–1031
[137] AnnéPR, Machtay M, Rosenthal DI, et al. A phase II trial subcutaneous amifostine and radiation therapy in patients with head–neck cancer. Int. J. Radiat. Oncol. Biol. Phys. 2007, 67, 445–452
[138]Srinivasan V. Radioprotection, pharmacokinetic and behavioural studies in mouse implanted with biodegradable drug (amifostine) pellets. Int. J. Radiat. Biol. , 2002, 78, 535–543
[139] Ozsahin M, Betz M, Matzinger O, et al. Feasibility and efficacy of subcutaneous amifostine therapy in patients with head and neck cancer treated with curative accelerated concomitant-boost radiation therapy. Arch. Otolaryngol. Head Neck Surg. 2006, 132, 141–145
[140]Anne PR. and Curran WJ. A phase II trial of subcutaneous amifostine and radiation therapy in patients with head and neck cancer. Semin. Radiat. Oncol., 2002, 12, 18–19
[141] Maisin JR, Albert C, Henry A, et al. Reduction of short-term radiation lethality by biological response modifiers given alone or in association with other chemical protectors. Radiat. Res. 1993, 135(3), 332–337
[142] Landauer MR, Castro CA, Benson KA, et al. Radioprotective and locomotor responses of mice treated with nimodipine alone and in combination with WR-151327. J. Appl. Toxicol. 2001, 21, 25–31
[143]Seed TM. Radiation protectants: current status and future prospects. Health Phys., 2005, 89, 531–545
[144] Vitolo JM, Cotrim AP, Sowers AL, et al. The stable nitroxide tempol facilitates salivary gland protection during head and neck irradiation in a mouse model. Clin. Cancer Res. 2004, 10, 1807–1812
[145] Cotrim AP, Sowers AL, Lodde BM, et al. Kinetics of tempol for prevention of xerostomia following head and neck irradiation in a mouse model. Clin. Cancer Res. 2005, 11, 7564–7568
[146] Hahn SM, Krishna MC, DeLuca AM, et al. Evaluation of the hydroxylamine tempol-H as an in vivo radioprotector. Free Radic. Biol. Med. 2000, 28, 953–958
[147] Martin RF, Broadhurst S, Reum ME, et al. In vitro studies with methylproamine: a potent new radioprotector. Cancer Res. 2004, 64, 1067–1070
[148]Celaries, B. Synthesis and radioprotective study of new siladithioacetals and germadithioacetals. Appl. Organometal. 2003, 17, 561–569
[149] Martin RF, Broadhurst S, D'Abrew S, et al. Radioprotection by DNA ligands. Br. J. Cancer, 1996, 74, 99–101
[150] Epperly MW, Defilippi S, Sikora C, et al. Intratracheal injection of manganese superoxide dismutase (MnSOD) plasmid/liposomes protects normal lung but not orthopedic tumors from irradiation. Gene Ther. 2000, 7, 1011–1018
[151] Vujaskovic Z, Batinic-Haberle I, Rabbani ZN, et al. A small molecular weight catalytic metalloporophyrin antioxidant with superoxide dismutase (SOD) mimetic properties protects lung from radiation-induced injury. Free Radic. Biol. Med. 2002, 33, 857–863
[152] Guo H, Seixas-Silva JA Jr, Epperly MW, et al. Prevention of radiation-induced oral cavity mucositis by plasmid/liposome delivery of the human manganese superoxide dismutase (SOD2) transgene. Radiat. Res. 2003, 159, 361–370
[153] Epperly MW, Gretton JA, DeFilippi SJ, et al. Modulation of radiation-induced cytokine elevation associated with esophagitis and esophageal stricture by manganese superoxide dismutase-plasmide/liposome (SOD2-PL) gene therapy. Radiat. Res. 2001, 155, 2–14
[154] Epperly MW, Kagan VE, Sikora CA, et al. Manganese superoxide dismutase-plasmid/liposome (MnSOD-PL) administration protects mice from esophagitis associated with fractionated radiation. Int. J. Cancer, 2001, 96, 221–231
[155] Epperly MW, Carpenter M, Agarwal A, et al. Intraoral manganeses superoxide dismutase-plasmid/ liposome (MnSOD-PL) radioprotective gene therapy decreases ionizing irradiationinduced murine mucosal cell cycling and apoptosis. In Vivo, 2004, 18, 401–410
[156] Epperly MW, Wegner R, Kanai AJ, et al. Effects of MnSOD-plasmid liposome gene therapy on antioxidant levels in irradiated murine oral cavity orthopedic tumors. Radiat. Res. 2007, 167, 289–297
[157] Somack R, Saifer MG, Williams LD. et al. Preparation of long-acting superoxide dismutase using high molecular weight poly-ethylene glycol (41,000–72,000 Daltons). Free Radic. Res. Commun. 1991, 12–13, 553–562
[158] Vajragupta O, Boonchoong P, Sumanont Y, et al. Manganese-based complexes of radical scavengers as neuroprotective agents. Bioorg. Med. Chem. 2003, 11, 2329–2337
[159] Emami S, Hosseinimehr SJ, Taghdisi SM, et al. Kojic acid and its manganese and zinc complexes as potential radioprotective agents. Bioorg. Med. Chem. Lett. 2007, 17, 45–48
[160]Sorenson, J.R.J. Cu, Fe, Mn, and chelates offer a medicinal chemistry approach to overcoming radiation injury. Curr. Med. Chem. 2002, 9, 639–662
[161]Herodin F, and Drouet M. Cytokine-based treatment of accidentally irradiated victims and new approaches. Exp. Hematol., 2005, 33, 1071–1080
[162]于景敏,孟志云,窦桂芳.粒细胞集落刺激因子的研究新进展.中国实验血液学杂志,2008,16(2):452—456.
[163]克晓燕,贾廷珍,王继军,等.医源性急性放射病的l临床探讨.中华放射医学与防护杂志,2006,26(1):15—19.
[164] Kim JY, Oh SJ, Park HK, et al. Radioprotective effects of various cytokines in peripheral blood mononuclear cells and C3H mice. Oncol. Rep. 2005, 13, 1177–1183
[165] Hudak S, Leach MW, Xu Y, et al. Radioprotective effects of flk2/flt3 ligand. Exp. Hematol. 1998, 26, 515–522
[166] Jalal Hosseinimehr S, Inanami O, Hamasu T, et al. Activation of C-kit by stem cell factor induces radioresistance to apoptosis through ERK-dependent expression of survivin in HL60 cells. J. Radiat. Res. 2004, 45, 557–561
[167] LeguéF, Guitton N, Brouazin-Jousseaume V, et al. Il-6 key cytokine in vitro and in vivo response of sertoli cells to external gamma irradiation. Cytokine, 2001, 16, 232–238
[168] Neta R, Vogel SN, Oppenheim JJ, et al. Radioprotection with interleukin-1: comparison with other cytokines. Prog. Immunol. 1986, 6, 900–908
[169] Singh VK, Srinivasan V, Seed TM, et al. Radioprotection by N-palmitoylated nanopeptide of human interleukin-1b. Peptide ,2005, 26, 413–418
[170]Streeter PR. Activation of the G-CSF and Flt-3 receptors protects hematopoietic stem cells from lethal irradiation. Exp. Hematol. 2003, 31, 1119–1123
[171] Kashiwakura I, Inanami O, Takahashi K, et al. Protective effects of thrombopoietin and stem cell factor on x-irradiated CD34+ megakaryocytic progenitor cells from human placental and umbilical cord blood. Radiat. Res. 2003, 160, 210–216
[172] Patchen ML, MacVittie TJ, Brook I. et al. Glucan-induced hematopoietic and immune stimulation: therapeutic effects in sublethally and lethally irradiated mice. Meth. Find. Exp. Clin. Pharmacol. 1986, 8, 151–155
[173] Song JY, Han SK, Bae KG, et al. Radioprotective effects of ginsan, an immunomodulator. Radiat. Res. 2003, 159, 768–774
[174]Rya KG,McMinn A,Mitchell KA ,et a1.Mycosporine like amino acids in Antarctic sea ice algae,and their response to UVB radiation.Z Naturforsch,2002,57(5-6):471-477
[175]杜宁,高天翔,缪锦来,等.4种南极冰藻中抗紫外辐射活性化合物类菌胞素类氨基酸(MAAs)的初步研究.中国海洋药物杂志,2007,26(4):5-10
[176]吴晓曼,杨明亮,黄晓兰,等.海带多糖的抗辐射作用与脾细胞凋亡.武汉大学学报(医学版),2004,25(3):239-241
[177]吴显劲,孟庆勇,袁汉尧.琼枝麒麟菜多糖对辐射损伤小鼠腹腔巨噬细胞的影响.中国职业医学,2007,34(4):287-291
[178]吴显劲,孟庆勇.琼枝麒麟菜多糖对γ射线照射小鼠胸腺细胞周期及细胞增殖的影响.中国辐射卫生,2005,14(4):6-8
[179]吴显劲,盂庆勇.琼枝麒麟菜多糖对γ射线照射小鼠脾细胞周期及细胞增殖的影响.中国职业医学,2006,33(2):12—14
[180]王海青,李翊.海藻低聚糖对放射损伤的防护作用研究.中国辐射卫生,2009,18(1):33-35
[181]侯军峰,张盈华.中草药对造血和免疫系统放射损伤的防护作用及其机理探讨.中国中西医结合杂志,2000,20(6):469-472
[182]Kim IT,Park J,Nam JH,et a1.In-vitro and in-vivo anti-inflammatory and antinocieeptive efects of the methanol extract of the roots of Morinda ofieinalis.J Pharm Pharmacol,2005,57(5):607-615
[183] Stickney DR, Dowding C, Garsd A, et al. 5-Androstenediol stimulates multilineage hematopoiesis in rhesus monkeys with radiation-induced myelosuppression. Int. Immunopharmacol. 2006, 6, 1706–1713
[184] Stickney DR, Dowding C, Authier S, et al. 5-Androstenediol improves survival in clinically unsupported rhesus monkeys with radiation-induced myelosuppression. Int. Immunopharmacol. 2007, 7, 500–505
[185] Safeukui I, Mangou F, Malvy D, et al. Plasmodium bergheri: dehydroepiandrosterone sulfate reverses chloroquino-resistance in experimental malaria infection; correlation with glucose 6-phosphate dehydrogenase and glutathione synthesis pathway. Biochem. Pharmacol. 2004, 68, 1903–1910
[186]夏贞彪,王建国.中华放射医学与防护杂志,1994,14(5):322
[187]王月英,王汝勤,赵忠萍.中华放射医学与防护杂志,2005,25(1):39-40.
[188] Komarova EA, Chernov MV, Franks R, et al. Transgenic mice with p53-responsive lacZ: p53 activity varies dramatically during normal development and determines radiation and drug sensitivity in vivo. EMBO J. 1997, 16(6):1391–1400.
[189]Vousden KH, Prives C. Blinded by the Light: The Growing Complexity of p53. Cell, 2009,137(3):413–431
[190] Komarov PG, Komarova EA, Kondratov RV et al. A chemical inhibitor of p53 that protects mice from the side effects of cancer therapy. Science. 1999, 285(5434):1733–1737.
[191] Strom E, Sathe S, Komarov PG, et al. Small-molecule inhibitor of p53 binding to mitochondria protects mice from gamma radiation. Nat Chem Biol. 2006, 2(9):474–479.
[192] Leonova KI, Shneyder J, Antoch MP, et al. A small molecule inhibitor of p53 stimulates amplification of hematopoietic stem cells but does not promote tumor development in mice. Cell Cycle. 2010, 9(7):1434–1443.
[193]Christophorou MA, Ringshausen I, Finch AJ, et al. The pathological response to DNA damage does not contribute to p53-mediated tumour suppression. Nature, 2006, 443(7108):214–217.
[194] Komarova EA, Kondratov RV, Wang K, et al. Dual effect of p53 on radiation sensitivity in vivo: p53 promotes hematopoietic injury, but protects from gastro-intestinal syndrome in mice. Oncogene. 2004, 23(19):3265–3271.
[195]Herodin F, Bourin P, Mayol JF, et al. Short-term injection of antiapoptotic cytokine combinations soon after lethal gamma-irradiation promotes survival. Blood, 2003, 101(7):2609–2616.
[196]Karin M. Nuclear factor-kappaB in cancer development and progression. Nature, 2006, 441(7092):431–436.
[197] Burdelya LG, Krivokrysenko VI, Tallant TC, et al. An agonist of toll-like receptor 5 hasradioprotective activity in mouse and primate models. Science. 2008;320(5873):226–230.
[198] Johnson SM, Torrice CD, Bell JF, et al. Mitigation of hematologic radiation toxicity in mice through pharmacological quiescence induced by CDK4/6 inhibition. J Clin Invest. 2010, 120(7):2528–2536.
[199]Weiss J. and Landauer M. Radioprotection by antioxidants. Ann. N.Y. Acad. Sci., 2000, 899, 44–60
[200]Kumar, S. Nutritional approaches to radiation protection. Mil. Med. 2002, 167, 57–59
[201] Satyamitra M, Devi PU, Murase H, et al. In vivo radioprotection by a-TMG: preliminary studies. Mutat. Res. 2001479, 53–61
[202] Satyamitra M, Uma Devi P, Murase H, et al. In vivo postirradiation protection by a vitamin E analog, a-TMG. Radiat. Res. 2003, 160, 655–661
[203] Singh VK, Shafran RL, Jackson WE 3rd, et al. Induction of cytokines by radioprotective tocopherol analogs. Exp. Mol. Pathol. 2006, 81, 55–61
[204]Keithahn C. and Lerchl A. 5-Hydroxytryptophan is a more potent in vitro hydroxyl radical scavenger than melatonin or vitamin C. J. Pineal. Res. ,2005, 38, 62–66
[205] Vijayalaxmi, Reiter RJ, Tan DX, et al. Melatonin as a radioprotective agent: a review. Int. J. Radiat. Oncol. Biol. Phys. 2004, 59, 639–653
[206] Koc M, Taysi S, Buyukokuroglu ME, et al. Melatonin protects rat liver against irradiation-induced oxidative injury. J. Radiat. Res. 2003, 44, 211–215
[207] Vijayalaxmi, Reiter RJ, Herman TS, et al. Melatonin and radioprotection from genetic damage: in vivo/in vitro studies with human volunteers. Mutat. Res. 1996, 371, 221–228
[208]Birdsall, T.C. The biological effects and clinical uses of the pineal hormone melatonin. Alt. Med. Rev. ,1996, 1, 94–102
[209] Lusardi P, Piazza E, Fogari R. Cardiovascular effects of melatonin in hypertensive patients well controlled by nifedipine: a 24-hours study. Br. J. Clin. Pharmacol. 2000, 49, 423–427
[210]ZHONG Jinyi,SU Shim.Chin J Ind Hyg Occup Dis,1999,17(4):211-213.
[211]CHEN Jiabo,WU Weipei.J Chin Med Mater, 2004,27(9):664-665.
[212]强亦忠,王崇道,邵源.几种制剂清除辐射所致自由基的ESR研究.辐射防护,1999,19(5):371.
[213]朱丹,袁芳,孟坤,等.黄酮类化合物的研究进展.中华中医药杂志,2007,22(6):387—389.
[214] Davis TA, Clarke TK, Mog SR, et al. Subcutaneous administration of genistein prior to lethal irradiation supports multilineage, hematopoietic progenitor cell recovery and survival. Int. J. Radiat. Biol. 83, 2007, 141–151
[215] Hong H, Landauer MR, Foriska MA, et al. Antibacterial activity of the soy isoflavone genistein. J. Basic Microbiol. 2006, 46, 329–335
[216] Jagetia GC, Reddy TK. et al. The grapefruit flavonone naringin protects against the radiation-induced genomic instability in the mice bone marrow: a micronucleus study. Mutat. Res. 2002, 519, 37–48
[217] Devi PU, Bisht KS, Vinitha M. et al. A comparative study of radioprotection by Ocimum flavonoids and synthetic aminothiol protectors in the mouse. Br. J. Radiol. 1998, 71, 782–784
[218] Shimoi K, Masuda S, Furugori M, Radioprotective effect of antioxidative flavonoids in gamma-ray irradiated mice. Carcinogenesis. 1994, 15(11):2669-72.
[219] Ganasoundari A, Devi PU, Rao BS. Enhancement of bone marrow radioprotection and reduction of WR-2721 toxicity by Ocimum sanctum. Mutat. Res. 1998, 397, 303–312
[220]李卫业,李群.辐射及活性氧对DNA的损伤以及芥子碱的保护作用.植物生理学报,1997,23(4),319-323.
[221]Thiyam U,Stockmann H.Schwarz K.Antioxidant activity of rapeseed phenolics and their interactions with tocopherols during lipid oxidation I J I.Am Oil Chem Soc,2006,83:523-528.
[222]利国威,应百平.骆驼蓬碱的辐射防护作用.中华放射医学与防护杂志,1993,13(4):252-254.
[223] Gupta D,Arora R,Garg AP,et a1.Radiation-induced damage to mitochondria and its modification by podophyllum hexandmm Royale in HepG2 cells.Mol Cell Bioehem,2003,247(3):25.
[224] Gupta D. AroraR,GargAP,et a1.Modification of radiation-damage to mitochondrial system in vivo by Pod ophylhm hexandrum:mechanistic aspects.Mol Cell Biochem,2004,266(1-2):65.
[225] Sajikumar S. God HC.Podophylam hexandmm prevents radiation induced neuronal damage in post-natal rats exposed in utero.Phytother Res,2003,17(7):761.
[226] God Hc.Salin CA,Prakash H.Protection of jejunal crypts by RH-3 (a preparation of Hippophae rhamnoides) against lethal whole body gamma irradiation.Phytother Res,2003,17(3):222.
[227] Prem KI,Samanta N. Goel HC.Modulation of chromatin organization by RH-3,a preparation of Hippophae rhamnoides,a possible role in radioprotection.MoI CelI Biochem,2002,238(1-2):1.
[228] Arora R,Sharma RK.Prasad J.et a1.Radioprotective efficacy of Hippophae rhamnoides.In Proceedings of the Seminar on Sea Buckthorn:A Resource for Environment.Health and Economy,2004,31 (2):21.
[229] Arora R,Gupta D.Garg AP.et a1.Radioprotection of mice liver mitochondria by Hippophae rhamnoides L.in rive.In Proceedings of 3rd Biennial Conference on Hyperthermic Oncology and Medicine.Pharmacol Ther,2003,39(2):347.
[230] God HC,Prem KI,Samanta N,et a1.Induction of DNA-protein cross-links by Hippophae rhanmoides,implications in radioprotection and cytotoxicity.Mol Cell Biochem,2003.245(1-2):57.
[231] GuptaD.AtomR,GuptaS,et a1.Radiation-induced oxidative damage to mitochondria and its modification by endogenous antioxidants in vivo:role of some herbal preparations.Indian J Nuclear Med,2003,18(3):14.
[232]Amra R,Gupta D.Sharma AK,et a1.Modification of radiation-induced damage in mammalian model systems by natural plant products:implications for radiation protection In Proceedings of the IUPAC.International Conference on Biodiversity and Natural Products,2004,33(4):56.
[233] Weiss JF, Landauer MR.Protection against ionizing radiation by antioxidant nutrients and phytochemicals.Toxicology,2003.1 89(1-2):1.
[234] Samarth RM, Kumar A.Mentha piperita(Linn )leaf extract provides protection against radiation induced chromosomal damage in bone marrow of mice.Indian J Exp Biol,2003,41(3):229.
[235] God HC,Prasad J,Singh S, et a1.Radioprotective potential of a herbal extract of Tinospora cordifolia.J Radiat Res,2004,45(1):61.
[236] Pahadiya S,Sharma J.Alteration of lethal efects of gamma rays in Swiss albino mice byTinospom cordifolia.Phytother Res,2003,17 (5):552.
[237]黄绵庆,阎春玲,窦梅,等.扇贝多肽对UVB损伤HaCat细胞的抗氧化作用.中国海洋药物. 2005 ;24 (3)26.
[238] Karsten Stahnke, Simone Fulda, Claudia Friesen, et al.Activation of apoptosis pathways in peripheral blood lymphocytes by in vivo chemotherapy. Blood, Nov 2001, 98: 3066 - 3073.
[239]吕丽爽.天然抗氧化剂低聚原花青素的研究进展.食品科技,2000,23(2):147-150
[240]董海东,陈静,陈慰峰.胸腺树突状细胞对胸腺细胞凋亡的促进作用.中国科学(C辑),1997,27(6):550-554.
[241]崔玉芳,高亚兵等,小鼠胸腺淋巴细胞辐射损伤特点和机理的研究。中国体视学与图像分析,1998;12(3):208-213.
[242] Green, D. R., Kroemer, G. (2004) The pathophysiology of mitochondrial cell death. Science 305, 626-629.
[243] Thorburn, A. (2004) Death receptor-induced cell killing. Cell Signal. 16, 139-144.
[244] Alvarez S, DranéP, Meiller A, et al. A comprehensive study of p53 transcriptional activity in thymus and spleen of gamma irradiated mouse: high sensitivity of genes involved in the two main apoptotic pathways. Int J Radiat Biol. 2006 , 82(11):761-70.
[245] Kang YH, Lee SJ. Role of p38 MAPK and JNK in enhanced cervical cancer cell killing by the combination of arsenic trioxide and ionizing radiation. Oncol Rep. 2008 , 20(3):637-43.
[246] Narang H, Krishna M. Effect of nitric oxide donor and gamma irradiation on MAPK signaling in murine peritoneal macrophages. J Cell Biochem. 2008 1;103(2):576-87.
[247] Ide T. Mechanism of cell proliferation--cell cycle, oncogenes, and senescence Yakugaku Zasshi. 2006, 126(11):1087~1115.
[248] Samuel T, Weber HO, Funk JO, et al. Linking DNA damage to cell cycle checkpoints. Cell Cycle. 2002, 162-168.
[249]刘扬,金光辉,刘树铮。流式细胞术在紫外线照射后细胞内活性氧检测中的应用。吉林大学学报,2004, 30(6): 975~977
[250] Singh RP, Dhanalakshmi S, Mohan S, et al. Silibinin inhibits UVB and epidermal growth factor-induced mitogenic and cell survival signaling involving activator protein-1 and nuclear factor-kappaB in mouse epidermal JB6 cells. Mol Cancer Ther. 2006, 5 (5): 1145~1153.
[251] Afaq F, Syed DN, Malik A, et al. Delphinidin, an anthocyanidin in pigmented fruits andvegetables, protects human HaCaT keratinocytes and mouse skin against UVB-mediated oxidative stress and apoptosis. J Invest Dermatol. 2007, 127 (1): 222~232.
[252]王崇道,强亦忠.中华放射医学与防护杂志,2002,22(6):461-463
[253] Svobodova A, Walterova D, Vostalova J. Ultraviolet light induced alteration to the skin. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2006, 150 (1): 25~38.
[254] Bras M, Queenan B, Susin SA. 2005. Programmed cell death via mitochondria: Different modes of dying. Biochemistry Biokhimiia 70:231–239.
[255] Klener P Jr, Andera L, Klener P, Necas E, Zivny′J. 2006. Cell death signalling pathways in the pathogenesis and therapy of haematologic malignancies: Overview of apoptotic pathways. Folia Biologica 52:34–44.
[256] Chen M, Wang J. Initiator caspases in apoptosis signaling pathways. Apoptosis,2002, 7, 313-319.
[257] Yang J, Liu X, Bhalla K, et al. Prevention of apoptosis by Bcl-2: release of cytochrome c from mitochondria blocked. Science,1997,275, 1129-1132.
[258] Zhu XF,Zhang XS,Li ZM,et al.Apoptosis induced by ceramide in hepatocellelar carcinoma Bel7402 cells.Acta Pharmacol Sin,2000,21:225～228
[259] Harris MH, Thompson CB. The role of the Bcl-2 family in the regulation of outer mitochondrial membrane permeability. Cell Death Differ, 2000, 7(12):1182-1191.
[260] Kuwana T, Mackey MR, Perkins G. Bid, Bax and lipids cooperate to form supramolecular openings in the outer mitochondrial membrane.Cell, 2002, 111(3):331-342.
[261] Wu Y, Xing D, Chen WR. Single cell FRET imaging for determination of pathway of tumor cell apoptosis induced by photofrin-PDT, Cell Cycle, 2006, 5:729-734.
[262] Hengartner MO, Horvitz HR. C. elegans cell survival gene ced-9 encodes a functional homolog of the mammalian proto-oncogene bcl-2. Cell. 1994, 25;76(4):665-76.
[263] Hochman A, Sternin H, Gorodin S, et al. Enhanced oxidative stress and altered antioxidants in brains of Bcl-2-deficient mice. J Neurochem. 1998, 71(2):741-8.
[264] Kulms D, Zeise E, P?ppelmann B, et al. DNA damage, death receptor activation and reactive oxygen species contribute to ultraviolet radiation-induced apoptosis in an essential and independent way. Oncogene. 2002 ,29;21(38):5844-51.
[265] Chinnaiyan et al., 1996; Kischkel et al., 2001; Seol et al., 2001; Kang et al., 2003
[266] Snopov SA, de Gruijl FR, Roza L, et al. Immunochemical study of DNA modifications in the nuclei of UV-damaged lymphocytes. Photochem. Photobiol. Sci 2004, 3: 85~90.
[267] Staniforth V, Chiu LT, Yang NS. Caffeic acid suppresses UVB radiation-induced expression of interleukin-10 and activation of mitogen-activated protein kinases in mouse. Carcinogenesis. 2006, 27 (9): 1803~1811.
[268] VAN LAETHEM A, NYS K, VAN KELST S, et al. Apoptosis signal regulating kinase1 connects reactive oxygen species to p38 MAPKinduced mitochondrial apoptosis in UVBirradiated human keratinocytes. Free Radic Biol Med, 2006,41(9):1361.
[269]于爽,郭沈波,严州萍,等.扇贝多肽对UVB损伤HaCa T细胞ERKs/MAPKs通路的影响.齐鲁医学杂志, 2006, 21(3):189-192.
[270] Yin Z M, Sima J, WU Y F, et al. The effect of C-terminal fragment of JNK2 on the stability of p53 and cell proliferation. Cell Res, 2004, 14(5): 434~438
[271] Martindale J L, Holbrook N J. Cellular response to oxidative stress: signaling for suicide and survival. J Cell Physiol, 2002, 192(1): 1~15
[272] Kennedy NJ, Cellurale C, Davis RJ. A radical role for p38 MAPK in tumor initiation. Cancer Cell 2007, 11: 101-103.
[273] Kharbanda S, Saxena S, Yoshida K, et al. Translocation of SAPK/JNK to mitochondria and interaction with Bcl-x(L) in response to DNA damage. J Biol Chem, 2000, 275(1): 322~327
[274] Lei K, Davis R J. JNK phosphorylation of Bim-related members of the Bcl2 family induces Bax-dependent apoptosis. Proc Natl Acad Sci USA, 2003, 100(5): 2432~2437
[275] Matsui Y, Tsuchida Y, Keng PC. Effects of p53 mutations on cellular sensitivity to ionizing radiation. Am J Clin Oncol. 2001, 24(5) 486-490.
[276] Bassett EA, Wang W, Rastinejad F, et al. Structural and functional basis for therapeutic modulation of p53 signaling. Clin Cancer Res. 2008, 15, 14(20):6376-86.
[277] Trinei M, Giorgio M, Cicalese A, et al. A p53-p66Shc signalling pathway controls intracellular redox status, levels of oxidation-damaged DNA and oxidative stress-induced apoptosis. Oncogene. 2002, 30;21(24):3872-8.
[278] Flatt PM, Price JO, Shaw A, et al. Differential cell cycle checkpoint response in normal human keratinocytes and fibroblasts. Cell Growth Differ. 1998, 9(7):535-43.
[279] Taylor WR,Stark GR.Regulation of the G2/M transition by p53.Oncogene,2001,20(15):1803～1815.
[280] Foijer F, te Riele H. Check, double check: the G2 barrier to cancer. Cell Cycle. 2006, 5(8):831-6.