羧甲基-β-1,3-葡聚糖对人肝癌HepG2细胞的放射增敏作用

本研究旨在探讨羧甲基-β-1,3葡聚糖（CMG）对人肝癌HepG2细胞X射线或12C6+离子束辐射敏感性的影响。首先用CCK-8法检测CMG对HepG2细胞的生长抑制情况,得到半数抑制浓度（IC50）为120.6μg/mL。用浓度为0.1×IC50的CMG预处理HepG2细胞24 h,再给予2 Gy X射线或12C6+离子束辐照（CMG+辐照组）;CMG未处理组直接接受2 Gy X射线或12C6+离子束辐照（辐照组）。对比分析辐照组和CMG+辐照组细胞的克隆存活、DNA损伤、凋亡与周期分布、细胞内活性氧（ROS）水平。发现:与X射线辐照组相比,相同剂量的12C6+离子辐照组克隆存活率更小,DNA损伤和周期阻滞更加严重,细胞凋亡率和细胞内ROS水平也更高。与单独X射线或12C6+离子束辐照组相比,CMG+辐照组克隆存活率明显降低,细胞凋亡率随辐照后CMG作用时间的延长而明显增加,CMG使辐照后细胞内ROS维持在一个较高的水平,同时CMG明显加重了单独辐照诱导的DNA损伤和周期阻滞。结果表明,与X射线相比,HepG2细胞对相同剂量的12C6+离子辐射更敏感;CMG可增加HepG2细胞对X射线或12C6+离子辐射的敏感性;CMG可能通过增加受照HepG2细胞内的ROS水平,加剧辐照诱导的DNA损伤,促进辐射诱导细胞凋亡而起到辐射增敏作用。This study aims to investigate the effect of carboxymethy-β-1, 3-glucan (CMG) on the sensitivity of human hepatoma HepG2 cells to X-rays or 12C6+ ions irradiation. First, the inhibitory effect of CMG on the growth of HepG2 cells was detected by CCK-8 assay, and the half maximal inhibitory concentration (IC50) was 120.6 μg/mL. HepG2 cells were pretreated with CMG at a concentration of 0.1×IC50 for 24 h and then irradiated with 2 Gy X-ray or 12C6+ ion beams (CMG + irradiation group). CMG untreated group was directly irradiated by 2 Gy X-rays or 12C6+ ions beam (irradiation group). The clone survival, DNA damage, cell apoptosis, cell cycle distribution, and intracellular reactive oxygen species (ROS) levels in irradiation group and CMG + irradiation group were comparatively analyzed. The results showed that the clone survival rate was lower, DNA damage and cycle arrest were more serious, and the rate of apoptosis and intracellular ROS levels were higher in 12C6+ ions irradiation group than those in the same dose of X-rays irradiation group. Compared with X-rays or 12C6+ ions irradiation group, the clone survival rate of CMG + irradiation group was significantly decreased, and the apoptosis rate significantly increased with the prolongation of CMG treatment post-irradiation; CMG maintained intracellular ROS at a higher level after irradiation, CMG also significantly aggravated radiation-induced DNA damage and cycle arrest. These results indicated that HepG2 cells were more sensitive to 12C6+ ions radiation than those at the same dose of X-rays. CMG increased the sensitivity of HepG2 cells to X-rays or 12C6+ ions irradiation by increasing intracellular ROS level, exacerbating radiation-induced DNA damage and promoting radiation-induced apoptosis in irradiated HepG2 cells.     

12C和X射线辐照人肺癌细胞H1299的生物学效应

用高传能线密度（LET）的12C离子束和低LET的X射线辐照体外培养的非小细胞肺癌H1299(p53基因缺失), 研究它们的辐照生物学效应的差异。 用克隆形成率法测定了细胞对射线的辐射敏感性; 用AnnexinV/PI试剂盒检测了细胞早期凋亡; 用流式细胞仪检测了细胞周期变化。 实验结果表明, 12C离子束辐照H1299细胞的存活率明显低于用X射线辐照的; 12C离子束引起H1299细胞的早期凋亡率明显高于X射线辐照引起的, 且持续时间更长; 12C离子束引起的H1299细胞G2/M期的抑制更明显。 说明H1299细胞对高LET的12C离子束的辐射敏感性高于对X射线的, 重离子对p53基因缺失型肿瘤的治疗可实施较低的照射剂量、 较少的照射次数和较长的时间间隔。     

^12C和X射线辐照人肺癌细胞H1299的生物学效应

用高传能线密度（LET）的^12C离子束和低LET的X射线辐照体外培养的非小细胞肺癌H1299（p53基因缺失）,研究它们的辐照生物学效应的差异。用克隆形成率法测定了细胞对射线的辐射敏感性;用AnnexinV/PI试剂盒检测了细胞早期凋亡;用流式细胞仪检测了细胞周期变化。实验结果表明,^12C离子束辐照H1299细胞的存活率明显低于用X射线辐照的;^12C离子束引起H1299细胞的早期凋亡率明显高于X射线辐照引起的,且持续时间更长;^12C离子束引起的H1299细胞G2/M期的抑制更明显。说明H1299细胞对高LET的^12C离子束的辐射敏感性高于对X射线的,重离子对p53基因缺失型肿瘤的治疗可实施较低的照射剂量、较少的照射次数和较长的时间间隔。     

辐照诱导人正常肝细胞系HL-7702 细胞远后的微卫星不稳定性

采用高传能线密度(LET) 的12C6+离子束和低LET 的X 射线辐照人正常肝细胞系HL-7702 细胞,利用微卫星不稳定性(MSI) 检测来分析直接受照射细胞和通过转移培养基方式旁细胞传代八代子细胞以MSI 表征的远后效应。实验结果表明,12C6+离子束诱导的远后效应较X射线的低;旁细胞的远后效应较直接受照射细胞的高;辐射引起的MSI 与杂合性丢失(LOH) 的发生率具有位点特异性。结果提示,重离子放射治疗较X 射线放射治疗对正常组织引发的辐射风险要小,可通过对MSI 高发位点的筛选来评估放疗后患者长期生存状况和二次癌症发生风险。Human normal liver cell line HL-7702 cells were irradiated with high linear energy transfer (LET) 12C6+ ions and low-LET X-rays, respectively. Delayed effect in terms of microsatellite instability (MSI) in progenies of the directly irradiated cells and bystander cells, obtained in the way of medium transfer at the 8th passage postirradiation,were examined. The delayed effect induced by the high-LET 12C6+ ions was different from that induced by the low-LET X-rays, and a higher incidence of MSI was observed in the progenies of the cells after exposure to the X-rays than to the 12C6+ ions. We also found that the delayed effect in the progenies of the bystander cells was much more severe than thoseof directly irradiated cells. Furthermore, the events of MSI and loss of heterozygosity (LOH) induced by the ionizing radiations were not randomly distributed throughout the genome and specific loci existed indeed. These results imply that the radiation risk to normal tissues is lower in heavy ion therapy than in conventional X-ray radiotherapy, and the analysis of microsatellite loci with MSI high frequency occurrence can be applied to access long-term survival condition and second cancer risk for the patients after radiotherapy.     

彗星电泳检测 12C6+离子束辐照人类肝L02细胞的DNA损伤效应

以传能线密度为30 keV/μm的12C6+离子束辐照人类肝L02细胞, 利用彗星电泳技术检测了以DNA链断裂为生物终点的DNA辐射损伤效应。 CASP软件分析彗星图像, 主要检测尾部DNA（TDNA％）、 彗星全长（CL）、 尾长（TL）、 尾矩（TM）和Olive尾矩（OTM）等指标, SPSS 11.5软件进行统计学分析, 绘制并拟合TM\|剂量曲线。 结果显示, 辐照以剂量依赖的方式引起L02细胞彗星图像各指标的增大, 且TM值与剂量线性正相关。 说明12C6+离子束对DNA有较强的致损伤效应, 且与剂量正相关。 研究为正确评价重离子对人体正常组织的辐射风险及危害提供了一定的基础数据和依据。     

两种保护剂对C离子诱导小鼠急性肝损伤的应答

比较了N-乙酰半胱氨酸(NAC)及乙酰左旋肉毒碱(ALCAR)对12C6+离子照射小鼠的损伤效应,并探讨了其可能的作用机制。利用4Gy剂量的12C6+离子束对预先给予NAC(100mg/kg)和ALCAR(100mg/kg)保护的昆明小鼠进行单次全身照射。随后检测肝组织中总抗氧化能力(TAC)、DNA单链断裂和细胞凋亡率。结果显示,与照射对照组相比,提前给予NAC和ALCAR均极显著地增强了肝组织的抗氧化能力(P0.001),减轻了12C6+离子导致的肝组织中DNA断裂(P0.001)和细胞凋亡(P0.001)。此外,还发现ALCAR组抗重离子辐照损伤的能力显著地高于NAC组(P0.05)。实验结果提示了NAC和ALCAR可通过抵御组织内的氧化胁迫,阻止DNA链的断裂和细胞的凋亡,实现对C离子辐照损伤的保护效应。而且ALCAR比NAC可能更适合成为有潜力、有希望的抗C重离子辐射药物。     

12C6+离子束辐照黄花蒿干种子当代生物学效应

利用12C6+重离子束对黄花蒿干种子辐照后,利用发芽率、根长、下胚轴长和株高4个指标研究不同剂量12C6+离子束辐照对黄花蒿的生物学效应。结果表明,随着辐照剂量的增加,黄花蒿的存活率和根长都呈现逐渐降低的趋势,而下胚轴长先上升后下降,株高总体呈现下降的趋势,但在60和90 Gy同时存在矮化与增高的植株。利用SRAP （sequence related amplified polymorphism）技术对辐照后M1代的黄花蒿植株进行研究,结果表明对照组和处理组之间的差异体现为特异性条带的变化。综合分析表明,12C6+的重离子辐照黄花蒿干种子可以产生显著的当代损伤效应,同时引起植物DNA的多态性变化。     

~(12)C~(6+)离子束辐照紫苏干种子当代效应

利用兰州重离子研究装置(HIRFL)提供的12C6+离子束辐照紫苏干种子(辐照剂量为40,80和120Gy,剂量率4Gy/min),探讨了重离子束辐照对紫苏M1代的生物学效应。结果发现,经不同剂量的12C6+离子束辐照后,紫苏种子的发芽率、发芽势、存活率、株高、分枝数、单株产量和千粒重等生物学性状均发生了变化,其中发芽势、单株产量和千粒重随辐照剂量的提高而降低,且有明显的剂量效应关系,但发芽率、大田成活率、株高和分枝数却随辐照剂量的增大,呈现出明显的"抛物线"趋势;紫苏幼苗根尖细胞的微核率和染色体畸变率随辐照剂量增加呈线性增加关系。这表明:12C6+重离子束辐照紫苏种子,具有明显的当代损伤效应,在本试验剂量范围内,低剂量辐照对发芽率和成活率有促进作用。     

~(12)C~(6+)高能重离子辐照大葱损伤及其分子生物学效应

利用30,90,180Gy3种剂量的12C6+重离子束辐照大葱种子,研究其在细胞水平和农艺性状的诱变效应并进行RAPD分析。通过与M1代的研究结果比较后表明:经过不同剂量12C6+重离子照射后能有效地诱导大葱细胞形成微核和染色体畸变,这种诱变效应,在M2代仍然有所表现。M1代大葱结果期的株高、白长、花序直径和种子产量随辐照剂量增加产生明显差别,其中30Gy辐照组增幅最大。大葱总水溶性蛋白质和维生素C的含量在30Gy组中积累最多,在90Gy组有明显下降。与M1代一致,M2代中大葱染色体微核率及RAPD分析所得的DNA多态性比率仍然与辐照剂量呈正相关,但比率整体下降;说明高能量重离子辐照造成的DNA变异在M2代被修复和淘汰。     

重离子辐射提高腺病毒介导小鼠黑色素瘤细胞转染率的研究

探讨12C6+ 离子束辐射对用带有绿色荧光蛋白基因的缺陷性腺病毒（AdCMV GFP）转染小鼠黑色素瘤细胞(B16细胞系)的影响。 采用不同剂量的12C6+ 重离子束辐射经AdCMV GFP 转染的B16细胞， 利用流式细胞仪检测腺病毒的转染率。 结果表明， 12C6＋重离子束辐射能提高腺病毒对B16细胞的转染率， 且具有量效关系。 此外， 先转染后辐射法比起先辐射后转染法能更显著地提高转染率。The effect of 12C6+ beam irradiation on AdCMV GFP (a replication deficient recombinant adenoviral vector containing CMV promoter and green fluorescent protein) gene transfection efficiency for murine melanoma cell B16 has been investigated. B16 cells infected with AdCMV GFP were irradiated by different doses of 12C6+ beam. The transfection efficiency was assessed by flow cytometry (FCM). Results show that 12C6+ beam irradiation can improve tansfection efficiency of AdCMV GFP on murine melanoma cell B16 in a dose dependent manner. In addition， the tansfection efficiency in pre tranfection plus irradiation group is higher than that in pre irradiation plus tranfection group at the same dose irradiation dose.     

Pre-irradiation with low-dose ~(12)C~(6+) beam significantly enhances the efficacy of AdCMV-p53 gene therapy in human non-small lung cancer

The combination of ionizing radiation and gene therapy has been investigated. However, there are very few reports about the combination of heavy-ion irradiation and gene therapy. To determine if the pre-exposure to low-dose heavy ion beam enhances the suppression of AdCMV-p53 on non-small lung cancer (NSLC), the cells pre-irradiated or non-irradiated were infected with 20, 40 MOI of AdCMV-p53. Survival fraction and the relative biology effect (RBE) were determined by clonogenic assay. The results showed that the proportions of p53 positive cells in 12C6+ beam induced AdCMV-p53 infected cells were more than 90%, which were signifi-cantly more than those in γ-ray induced AdCMV-p53 infected cells. The pre-exposure to low-dose 12C6+ beam significantly prevented the G0/G1 arrest and activated G2/M checkpoints. The pre-exposure to 12C6+ beam significantly improved cell to apoptosis. RBEs for the 12C6+ + AdCMV-p53 infection groups were 30%-60%, 20%-130% and 30%-70% more than those for the 12C6+-irradiated only, AdCMV-p53 infected only, and γ-irradiation induced AdCMVp53 infected groups, respectively. The data suggested that the pre-exposure to low-dose 12C6+ beam significantly promotes exogenous p53 expression in NSLC, and the suppression of AdCMV-p53 gene therapy on NSLC.     

GANRA-5对X射线和~(12)C~(6+)离子辐射防护作用研究

研究了一种新的恶唑酮类衍生物GANRA-5对于人胚肺细胞MRC-5的辐射防护作用。以MTT评价其对于细胞的毒性,以γH2AX foci形成法检测其对于辐照后细胞中双链断裂的影响,发现其对于受到X射线和12C6+离子照射的细胞具有较强的辐射防护作用,并进一步发现其能够显著清除辐照后细胞内的自由基。这些结果表明,GANRA-5具有较低的细胞毒性,并能够通过清除自由基发挥较强的针对X射线和12C6+离子的辐射防护作用,有望开发为高效的辐射防护药物。     

12C6+ 离子束辐照对大鼠离体主动脉环内皮依赖性舒张功能的影响

利用兰州重离子研究装置(HIRFL) 提供的高能12C6+离子束(能量为300 MeV/u,剂量率为0.5 Gy/min) 辐照大鼠离体胸主动脉环,考察了12C6+离子束辐照对主动脉环内皮依赖性舒张功能的影响,并采用NBT 还原法测定血管环生成超氧阴离子(O2􀀀) 水平,加入外源性超氧化物歧化酶(SOD) 干预探讨了O2􀀀在内皮功能损伤中的作用。研究结果表明,2.0,4.0 和6.0 Gy 的12C6+离子束辐照大鼠胸主动脉环后,可致血管内皮依赖性舒张功能的剂量依赖性明显受损(P <0.01 vs control group),并可致血管环NBT 还原能力剂量依赖性增加(4.0 Gy 时,P <0.05;6.0 Gy 时,P <0.01 vs control group)。辐照前加入外源性SOD 对6.0 Gy 12C6+离子束辐照所致血管环NBT 还原能力升高有明显抑制作用(P <0.01),对血管环内皮依赖性舒张功能也有明显的保护作用(P<0.01),但辐照后10 min 加入外源性SOD,其保护作用明显不及前者。结论显示,12C6+ 离子束辐照大鼠胸主动脉环可致血管内皮功能受损,O2 清除剂SOD 对内皮功能受损有保护作用,说明O2􀀀介导了辐照所致内皮功能损伤。Heavy ion beam has many characteristics,and it is expected to be the most suitable radiation therapy technique for malignant tumor. It is lack of depth-understanding on the potential adverse reactions caused by using this technique, because heavy ion radiotherapy is applied to clinical for a short time. Studies have shown that the vascular injury plays a pivotal role in normal tissue damage induced in the conventional radiation therapy, but there was no research report on heavy ion beam irradiation-induced vascular injury. In the present study, the isolated aortic rings of rats were irradiated by 12C6+ ion beam (300 MeV/u, 0.5 Gy/min) delivered by HIRFL(Heavy Ion Research Facility in Lanzhou), the effects of 12C6+ ion beam irradiation on aortic rings with endothelium dependent diastolic function have been investigated.NBT reduction method was used for assaying the vascular ring formation of superoxide anion (O2􀀀) level, and the involvement of superoxide anion in endothelial function injury in rats was investigated through the intervention test of exogenous superoxide dismutase (SOD) on O2. The results showed that, the vascular endothelial dependent vasodilation was impaired significantly (P < 0:01 vs control group) by irradiation with 2.0, 4.0 and 6.0 Gy 12C6+ ion beam in a dosedependent manner, and the NBT reduction of vascular rings increased dose-dependently (P <0.05 at 4.0 Gy, P <0.01 at 6.0 Gy vs control group). Adding exogenous SOD before irradiation could significantly inhibit the increasing of NBT reduction (P<0.01), and also had protective effect on vascular endothelium dependent diastolic function (P<0.01), but 10 min after irradiation with exogenous SOD, its protective function was significantly less than before. Conclusion indicated that 12C6+ ion beam irradiation could cause endothelial function impaired, O2􀀀 scavenger SOD has a protective effect on endothelial dysfunction, suggesting that O2􀀀 mediates endothelial injury induced by heavy ion irradiation.     

和厚朴酚对非小细胞肺癌细胞的辐射增敏效应

研究了和厚朴酚（HNK）对非小细胞肺癌（NSCLC）细胞系A549和H1299对低线性能量转移（LET） X射线和高LET碳离子的辐射增敏效应。首先用CCK-8检测了HNK对A549和H1299细胞的生长抑制情况,发现20 μmol/L的HNK处理对细胞的生长抑制作用较弱。用该浓度HNK预处理细胞2 h后给予不同剂量X射线或碳离子的照射,克隆存活法检测细胞的辐射敏感性,Annexin-PI双染法检测细胞凋亡,γH2AX焦点法检测DNA的双链断裂（DSB）损伤。实验结果显示:与X射线相比,NSCLC细胞对碳离子更敏感,HNK预处理仅对碳离子照射有辐射增敏作用;与碳离子单独照射相比,HNK预处理联合碳离子照射诱导了更明显的细胞凋亡;在照射后24 h,HNK预处理联合碳离子照射引起的细胞γH2AX焦点阳性率维持在较高水平,而X射线照射没有这些效应。实验结果表明,HNK预处理抑制了NSCLC细胞DNA的DSB修复,诱导了细胞凋亡的发生,从而提高了细胞对碳离子的辐射敏感性。The radiosensitizing effect of Honokiol (HNK) on non-small cell lung carcinoma (NSCLC) cell lines A549 and H1299 to low-linear energy transfer (LET) X-rays and high-LET carbon ions was investigated in this study. First, the inhibitory effects of HNK on the growth of A549 and H1299 cells were detected by CCK-8 assay, and 20 μmol/L HNK treatment was found to induce a growth inhibitory effect slightly in these two cell lines. Cells were pre-treated with HNK and then irradiated with X-rays and carbon ions of different doses. Cellular radiosensitivity, apoptosis and DNA damage were analyzed by clonogenic survival, Annexin-PI staining and γH2AX foci, respectively. The results showed the cells were more sensitive to carbon ion irradiation compared to X-rays and the radiosensitization of HNK was only observed after carbon ion irradiation. Furthermore, the co-treatment led to higher apoptosis rate 48 h after irradiation and increased the positive rate of γH2AX foci 24 h after irradiation in A549 and H1299 cells compared with those in the groups treated with carbon ion irradiation alone. These phenomena were not observed after X-ray irradiation. Our data suggest that the pre-treatment with HNK inhibited DNA DSB repair, induced apoptosis and then enhanced the cellular radiosensitivity to carbon ions in NSCLC cells.     

12C6+离子预辐射对小鼠胸腺脾脏细胞周期进程的影响

以0, 0.05, 0.1, 0.25, 0.5 Gy 12C6+ 离子全身预辐照昆明小鼠, 间隔4 h后再对小鼠进行4 Gy全身辐射。 辐照后12 h用流式细胞仪检测小鼠胸腺脾脏细胞在各细胞周期时相的百分率, 同时用单细胞电泳检测受辐射小鼠胸腺脾脏细胞DNA损伤程度。 结果显示, 相对于大剂量预照射组, 各低剂量预照射组胸腺细胞S期细胞百分率显著减少; 脾脏细胞G0/G1期细胞百分率明显减少; 同时胸腺脾脏细胞的拖尾率及拖尾长度明显减少, 以0.1 Gy预辐照效果最为明显。 这些结果表明, 低剂量预辐射处理可以减弱胸腺细胞的S期阻滞及脾脏细胞的G1期阻滞, 并明显减轻胸腺脾脏细胞的DNA损伤程度。     

重离子和X射线对人微血管内皮细胞血管生成的抑制作用

研究了X 射线和重离子照射对人微血管内皮细胞的增殖、迁移、管样结构形成及基质金属蛋白酶表达的影响。Transwell 迁移实验结果显示,照射24 h 后,非毒性照射剂量照射能抑制HMEC-1 细胞的迁移,且重离子照射抑制内皮细胞迁移能力较X 射线的强。基质胶实验显示,重离子照射可显著抑制自发性管样结构的形成,但X 射线照射的抑制作用不明显。同时,明胶酶谱法证实了重离子照射可明显抑制HMEC-1 细胞中基质金属蛋白酶( MMP-2 和MMP-9 ) 的表达,而X 射线照射对此类酶几乎无任何影响,显示了重离子较X射线的肿瘤放疗优势所在。The study aims to explore the effect of 12C6+ ion and X-ray on proliferation, migration, tube formation and MMPS of human microvascular endothelial cells ( HMEC-1 ). Transwell migration experiment showed that the radiation could inhibit the migration of HMEC-1 in sub-lethal dose 24 h after irradiation. Furthermore, the inhibition ability of 12C6+ ion was stronger than that of X-ray. Matrigel experiment indicated that 12C6+ ion suppressed the tube formation of HMEC-1 spontaneously. However, the inhibitory effect of X-ray had no significance. Meanwhile, Gelatin Zymography showed the expression of MMP-2 was inhibited obviously by 12C6+ ion, while X-ray had little effect on the expression of MMP-2. In conclusion, 12C6+ ion is superior to X-ray in radiotherapy of tumor.     

内质网应激对碳离子辐照宫颈癌HeLa 细胞的影响

利用不同剂量的碳离子辐照二硫苏糖醇(2.5 mmol/L) 预处理的HeLa 细胞,探讨了内质网应激反应对碳离子辐照宫颈癌HeLa 细胞的影响。实验发现:与单独辐照组相比,二硫苏糖醇联合碳离子辐照后细胞的存活率下降,而凋亡率增加;二硫苏糖醇联合碳离子辐照加重了碳离子辐照引起的细胞周期阻滞;且联合辐照组的自噬被明显激活。结果表明,持续的内质网应激可改变宫颈癌HeLa 细胞对碳离子辐照反应,且二硫苏糖醇可能通过影响HeLa 细胞的自噬性细胞死亡通路发挥作用。To investigate the effect of endoplasmic reticulum stress on HeLa cells to 12C6+ ion irradiation,HeLa cells were pretreated with 2.5 mmol/L dithiothreitol and irradiated by 12C6+ ions with different doses.The results showed that, compared with IR alone, dithiothreitol combined with carbon ion irradiation caused HeLa cell survival decreased, and the apoptosis increased. Moreover, dithiothreitol and carbon ion radiation combination treatment led to a significant increase of G2/M phase, and autophagy was activated obviously in combination treatment group. The results imply that continuous endoplasmic reticulum stress can change the response of HeLa cells to 12C6+ irradiation, and dithiothreitol may affect HeLa cells through the autophagy cell death pathway.     

12C6+离子对阿维链霉菌累进辐照诱变效应研究

选用12C6+ 离子束对阿维链霉菌诱变选育高产菌株与原始菌株进行辐照诱变, 研究其累进辐照效应。实验结果表明,在辐照剂量为10 Gy时, 原始菌株比诱变高产菌株存活率高, 抗辐射能力强;辐照剂量高于30 Gy时,诱变高产菌株比原始菌株存活率高, 抗辐射能力强。原始菌株正突变率最高的辐照剂量为50 Gy, 致死率99.43%,正突变率最高, 达34.2%;对诱变高产菌株辐照剂量为30 Gy,致死率94.97%,正突变率最高, 达23.5% 。累进辐照效应降低了最佳辐照剂量。 Mutagenic effect on the mutant high producing strain ZJAV Y1 203 and the original strain ZJAV A1 irradiated by ion beam of 12C6+ have been investigated. The experimental results indicated that the original strain has higher survival rate and stronger resistance to radiation than mutant high producing Strain at dose of 10 Gy. The mutant high producing strain has higher survival rate and stronger resistance to radiation than the original strain at the dose higher than 30 Gy. The lethality was 97% and the highest rate of orthomutation was 34.2%, when ZJAV A1 was irradiated by 50 Gy 12C6+ beam. The lethality was 94.97% and the highest rate of orthomutation was 23.5% when ZJAV Y1 203 was irradiated by 30 Gy 12C6+ beam. The best radiation dose is decreased by progressivity irradiation.