125 I-脱氧尿嘧啶核苷对肝癌细胞HepG2生长的抑制作用

目的评价125I-脱氧尿嘧啶核苷(UdR)对肝癌细胞HepG2生长的抑制作用及影响因素.方法 HepG2细胞在含有125I-UdR培养基中培养后测量其放射性,观察HepG2细胞对125I-UdR的摄取;用细胞克隆形成法评价125I-UdR对HepG2细胞生长的抑制作用.结果 HepG2摄取125I-UdR量随培养基中125I-UdR浓度增加而增加,两者显著相关(r=0.99).HepG2对125I-UdR的摄取明显高于Na125I.HepG2细胞摄取125I-UdR后其生长受到抑制,两者呈明显负相关(r=-0.943),半数致死剂量(LD50)为(0.87±0.29) kBq/mL.125I-UdR组细胞存活分数明显低于Na125I组.结论 125I-UdR对HepG2细胞生长有明显抑制作用,HepG2细胞摄取125I-UdR量有浓度依赖性.     

3H-TdR与125I-UdR掺入淋巴细胞增殖的比较

目的 比较 ³H-TdR与 ¹²⁵I-UdR掺入淋巴细胞的增殖效应。方法 用 ³H-TdR与 ¹²⁵I-UdR掺入法测定淋巴细胞和Daudi淋巴瘤细胞的增殖效应。结果 ³H-TdR和 ¹²⁵I-UdR在正常淋巴细胞中的掺入率分别为20.95%±1.06%和1.00%±0.04%,在Daudi淋巴瘤细胞中的掺入率分别为29.94%±4.10%和6.02%±0.73%。 ³H-TdR在细胞中的掺入率明显高于 ¹²⁵I-UdR;且 ³H-TdR和 ¹²⁵I-UdR在淋巴瘤细胞中的掺入率高于正常淋巴细胞。结论 就淋巴细胞而言,作为示踪剂 ¹²⁵I-UdR不能替代 ³H-TdR;但对于淋巴瘤细胞,能否代替 ³H-TdR有待于进一步研究。     

125I-UdR壳聚糖纳米微粒对肝癌细胞的内照射生物学效应

目的 评估¹²⁵I-UdR壳聚糖载药纳米微粒(¹²⁵I-UdR-CS-DLN)对肝癌细胞的内照射生物学效应.方法 采用激光共聚焦显微镜观察¹²⁵I-UdR-CS-DLN在肝癌细胞HepG2和人正常肝组织细胞HL-7702内的聚积和分布;通过MTT实验、流式细胞仪和单细胞凝胶电泳技术,评价内照射细胞生物学效应;采用TUNEL染色法观察兔肝原位肿瘤细胞经¹²⁵I-UdR-CS-DLN靶向治疗后的细胞凋亡.结果 纳米微粒作用30 min后,其在HepG2细胞质内的聚积大于HL-7702;当¹²⁵I-UdR-CS-DLN浓度大于37 kBq/ml时,HepG2细胞在纳米微粒作用后24、48 h的存活率显著低于HL-7702细胞(t=-4.46~6.31,P<0.05),且细胞周期G₁期阻滞明显, G₂/M期细胞明显受损;¹²⁵I-UdR-CS-DLN造成细胞DNA双链断裂的程度明显高于¹²⁵I-UdR,HepG2细胞的DNA损伤后修复能力显著低于HL-7702(Olive尾矩:t=2.94,P<0.05;彗尾DNA%:t=10.64,P<0.01);兔肝原位癌模型经介入被动靶向治疗后的TUNEL染色结果表明,¹²⁵I-UdR-CS-DLN可使兔肝原位肿瘤细胞产生明显的凋亡,而相同剂量¹²⁵I-UdR作用后肿瘤并未出现明显的凋亡.结论 ¹²⁵I-UdR-CS-DLN进入肝癌细胞的能力明显强于¹²⁵I-UdR,引起的DNA辐射损伤效应更强,可明显加剧肝癌细胞的凋亡,阻止DNA损伤修复.     

我国非铀矿山222Rn和220Rn水平初步调查研究

目的 测量非铀矿山²²²Rn、²²⁰Rn水平,了解我国矿山氡超标比率和矿工受照剂量。方法 根据典型抽样方法选择12个省17类44座矿山,采用LD-P分辨型探测器测量²²²Rn、²²⁰Rn累积浓度。结果 ²²²Rn、²²⁰Rn浓度呈对数正态分布,金属矿(25座,147处)²²²Rn浓度算数均值(AM)和几何均值(GM)分别为(1211±2359)和(311±5.5) Bq m³;²²⁰Rn浓度AM和GM分别为(269±700)和(71±4.4) Bq m³。非金属矿(18座,118处)²²²Rn浓度AM和GM分别为(98±207)和(55±2.5) Bq m³;²²⁰Rn浓度AM和GM分别为(60±76)和(38±2.4) Bq m³。测量地下矿井40处,其中6处²²²Rn浓度均值超过1000 Bq m³ (工作场所氡浓度限值),占抽样率15.0%;约有7%测点²²²Rn超过浓度3700 Bq m³ (我国铀矿冶氡浓度限值),个别测点超过10 000 Bq m³。井下和地面工作区室内²²²Rn平衡因子分别为0.33±0.15和0.47±0.18。²²⁰Rn平衡因子的波动范围较大,为0.001～0.032。地下矿山矿工的年均受照剂量约为8.15mSv。结论 我国金属矿山特别是有色金属矿井下²²²Rn浓度偏高的问题依然严重,值得关注和进行跟踪研究。     

125I粒子和60Co γ射线照射对A549及BEAS-2B细胞生物学效应的影响

目的 探讨¹²⁵I粒子和⁶⁰Co γ射线对非小细胞肺癌(NSCLC)A549细胞和正常支气管上皮BEAS-2B细胞生物学效应的影响。方法 A549、BEAS-2B细胞均行¹²⁵I粒子和⁶⁰Co γ射线不同剂量照射;集落形成实验检测细胞存活分数;流式细胞术检测细胞周期和细胞凋亡率;Western blot检测凋亡相关蛋白的表达水平。结果 A549细胞在4、6、8 Gy照射时,¹²⁵I粒子组细胞克隆存活分数较⁶⁰Co组降低更明显(t=6.06、9.42、4.90,P<0.05)。A549细胞在4 Gy时,G₁期细胞比例¹²⁵I粒子组为70.67%±1.49%,⁶⁰Co组为59.59%±0.71%(t=10.77,P<0.05);细胞凋亡率¹²⁵I粒子组为18.09%±0.73%,⁶⁰Co组为9.81%±0.16%(t=19.40,P<0.05)。¹²⁵I粒子照射明显上调Bax、cleaved Caspase-3蛋白的表达,同时下调Bcl-2蛋白的表达。但不同射线同一剂量或相同射线不同剂量下,BEAS-2B细胞的凋亡率及凋亡相关蛋白的表达无明显变化。结论 ¹²⁵I粒子持续低剂量率照射较⁶⁰Co γ射线高剂量率照射抑制A549细胞增殖的效应更明显。Bcl-2/Bax蛋白比失衡,最终致Caspase-3蛋白的活化在¹²⁵I粒子持续低剂量率照射抑制肿瘤细胞增殖的效应中可能发挥重要的作用。     

贵州省部分矿山放射性水平的评价

目的 调查和评价贵州省铝、锰、锑、磷、汞等部分矿山放射性水平。方法 对矿区氡气、钍气浓度进行累积1年的现场检测;采集矿石、矿山周围土壤进行放射性核素分析;对矿区γ辐射水平进行测量;对矿山渗透水进行总α、总β测量。结果 某铝矿山春、夏两季井下氡浓度水平为626.0～3866 Bq m³,秋、冬两季为38.9～655.0 Bq m³,全年平均值为1374 Bq m³;春、夏两季井下钍浓度水平为626.0～4834 Bq m³,秋、冬两季为40.9～344.0 Bq m³,全年平均值为1221 Bq m³。其余矿山均低于此水平。矿石放射性核素²²⁶Ra为6.9～511.9 Bq/kg、²³²Th为1.4～536.7 Bq/kg、⁴⁰K为<17.5～433.7 Bq/kg。γ外照射最高的为铝矿,平均值(87.0±8.1)×10^-8 Gy/h,最低的为锑矿,平均值(6.0±1.9)×10^-8 Gy/h。矿山井下水总α为小于探测下限～17.5(×10^-2Bq/L),总β为小于探测下限～37.4(×10^-2Bq/L)。结论 此次调查的部分矿山,大多采用机械和自然相结合的通风方式,通风情况较好。但铝矿井下的氡、钍浓度水平明显高于井外,全年平均值分别是井外的78倍和15倍;铝矿的γ外照射平均值(87.0±8.1)×10^-8 Gy/h,也明显高于贵州省γ天然辐射平均值(13.3×10^-8 Gy/h)。这将对该矿的矿工增加一定的附加剂量。     

125I-脱氧尿嘧啶核苷-壳聚糖载药纳米微粒的研制和鉴定

目的 研制直径100～200 nm的¹²⁵I-脱氧尿嘧啶核苷-壳聚糖载药纳米微粒( ¹²⁵I-UdR-CS-DLN),并进一步分析其药物缓释性能和肿瘤靶向性。方法 采用离子交联法制备CS纳米微粒,以单因素分析和正交试验优化制备条件和工艺;用动态透析法分析其释放特性;激光共聚焦显微镜观察其肿瘤靶向性。结果 按照CS浓度1 g/L,搅拌速度600 r/min,TPP浓度2 g/L,相对分子质量为3×10³的条件下得到平均粒径(70.39±5.12) nm的纳米微粒(PDI为0.16±0.012)。透射电镜观察其外观为规整的球形,大小均匀,分散度较好。在投药量为2.96 MBq/ml、pH值为5的条件下, ¹²⁵I-UdR-CS-DLN的载药量1253.55 MBq/g,包封率42.35%,具有明显的缓释作用。激光共聚焦显微镜观察结果证明肿瘤细胞在2 h内摄入的纳米粒子明显多于正常细胞。结论 成功制备了直径为(127.81±15.25) nm (PDI 为0.240±0.035)的 ¹²⁵I-UdR-CS-DLN,确定了最佳工艺条件。所制备的纳米粒子具有典型的长效缓释制剂特性,并具有肿瘤细胞被动靶向性,为 ¹²⁵I-UdR应用于肿瘤内照射治疗提供了更有效的途径。     

秦山核电站二期扩建工程运行后周围饮用水总放射性水平调查

目的 调查分析秦山核电站二期扩建工程正式投入运行后周围饮用水中的总放射性水平及变化趋势。方法 2010—2022年,每年分别在丰水期(5月)和枯水期(10月)采集秦山核电站周围30 km内的水源水、出厂水和末梢水,测定分析饮用水中总α、总β放射性活度浓度,并与国内不同核电站周围饮用水、无核电站地区周围饮用水总放射性水平进行比较。结果 水源水总α、总β放射性活度浓度均值分别为(0.021±0.019)和(0.204±0.058)Bq/L,出厂水总α、总β放射性活度浓度均值分别为(0.010±0.005)和(0.185±0.056)Bq/L,末梢水总α、总β放射性活度浓度均值分别为(0.012±0.007)和(0.170±0.058)Bq/L,均低于《生活饮用水卫生标准》规定的限值,3类水体在丰水期和枯水期监测结果差异均无统计学意义(P>0.05),与国内不同核电站周围饮用水以及无核电站地区周围饮用水总放射性水平接近。结论 二期扩建工程正式投入运行后,秦山核电站周围饮用水中总α、总β放射性水平处于本底水平且趋势平稳,低于国家标准指导水平。     

CD45单抗及188Re-亲和素二步法预定位对淋巴瘤Raji细胞的放射免疫效应研究

目的 探讨CD45单抗及¹⁸⁸Re-亲和素(Avidin)二步法预定位对人淋巴瘤Raji细胞的放射免疫效应。方法 ¹⁸⁸Re对CD45单抗及Avidin的标记采用直接标记法,采用纸层析法测定标记率及放化纯度。分析¹⁸⁸Re-CD45单抗与Raji细胞的体外结合能力,并进行体外竞争结合实验,采用CCK-8法测定二步法预定位组、¹⁸⁸Re-CD45单抗组、¹⁸⁸Re-Avidin组和¹⁸⁸ReO₄^-组对Raji细胞的增殖抑制效应,计算Raji细胞存活率和抑制率。结果 ¹⁸⁸Re-CD45单抗与Raji细胞的特异性结合率为(70.92±1.91)%,同时加入¹⁸⁸Re-CD45单抗和过量的CD45单抗,则细胞结合率平均为(7.96±0.87)%。二步法预定位组、¹⁸⁸Re-CD45单抗组、¹⁸⁸Re-Avidin组和¹⁸⁸ReO₄^-组对Raji细胞的增殖均有抑制作用,抑制率与放射性活度呈正相关(r=0.907~0.992,P<0.05);在相同放射性活度下,二步法预定位组在各时间点的抑制作用均高于¹⁸⁸Re-CD45单抗组、¹⁸⁸Re-Avidin组和¹⁸⁸ReO₄^-组(t=124.76~607.98,P<0.05)。结论 ¹⁸⁸Re-CD45单抗可特异性地与Raji细胞结合,CD45单抗及¹⁸⁸Re-Avidin二步法预定位对人淋巴瘤Raji细胞具有明显的抑制作用。     

2013—2020年辽宁红沿河核电站周围地区的食品放射性水平及公众内照射剂量研究

目的 评价辽宁红沿河核电站运行后对周边地区食品放射性水平的影响。方法 通过对2013年至2020年核电站运行期间周边30 km范围内食品放射性水平的分析,对比核电站运行前后及对照点的放射性水平,评估核电站的运行对当地食品放射性水平的影响。结果 当地食品中未发现¹³¹I、¹³⁴Cs、⁶⁰Co、⁵⁸Co、¹¹⁰Ag^m等人工放射性核素,天然放射性核素²³⁸U、²²⁶Ra、²³²Th、⁴⁰K均在正常本底水平,平均值分别为（0.088±0.053）、（0.155±0.178）、（0.314±0.388）和（81.3±18.1） Bq/kg （鲜重）。食品样品中人工放射性¹³⁷Cs活度浓度平均值为（0.013±0.010） Bq/kg （鲜重）。与对照点及运行前水平比较,放射性核素水平未见增加。结论 红沿河核电站的运行未对周边食品放射性水平带来影响。     

Association for Radiation Research

Two cell lines, CHO and GC, different in their tissue origin, were investigated with the aim of discovering the correlation between the level of ¹²⁵I-T₃ binding and chromosomal damage induced by ¹²⁵I decay. Incubation of cells with ¹²⁵I-T₃ has been performed in two exposure schedules: continuous incubation for one to six cell cycles and a pulse-chase schedule involving exposure for one cell cycle. The cellular uptake of ¹²⁵I-T₃, its compartmentization and kinetics were different in the two cell lines. GC cells contained about 7 times more ¹²⁵I-T₃ than CHO cells when incubated with the same external ¹²⁵I activity concentration (74 kBq of ¹²⁵I-T₃ ml^?1 medium). Approximately 70% of the cellular ¹²⁵I-T₃ was found in nuclei of GC cells and only 5% in the nuclei of CHO cells. During the long-term incubation of GC cells with 74 kBq of ¹²⁵I-T₃ ml^?1 medium, the ¹²⁵I activity concentration in cells and their nuclei initially decreased by a half, and thereafter reached a plateau after the third doubling time. In CHO cells and nuclei a very slow linear increase of ¹²⁵I activity was observed. In GC cells, micronucleus frequency was found to be correlated with nuclear ¹²⁵I activity. One cell cycle pulse labelling with 74 kBq of ¹²⁵I-T₃ ml^?1 medium caused a significant enhancement of micronucleus frequency above the control level during six doubling times, with a maximum at the first post-labelling doubling time. In GC cells continuously incubated with 74 kBq of ¹²⁵I-T₃ ml^?1 medium, the micronucleus frequency increased with the incubation time. A model of T₃ receptor-dependent dose delivery to nuclei of GC cells continuously incubated with ¹²⁵I-T₃ is proposed. The frequency of micronuclei in the CHO cell line continuously incubated with ¹²⁵I-T₃ did not differ significantly from the control, whereas in the pulse-chase schedule the mean frequency of micronucleated binuclear cells was lower during 4 post-labelling doubling times (significantly at the first and second post-labelling doubling time and insignificantly at the later doubling times) than in the control. Incubation of GC cells with various activity concentrations in medium for four cell cycles resulted in a linear increase of ¹²⁵I activity in cells and nuclei; however, with a saturation in the region of highest ¹²⁵I-T₃ concentrations used. The frequency of binuclear cells bearing micronuclei was linearly dependent on the nuclear ¹²⁵I-T₃ concentration.     

Chromosomal Abnormalities Induced by Iodine-125 in Mouse Germ Cells

Summary

Swiss albino male mice were injected intraperitoneally with 0, 185, 370 or 555 kBq (0, 5, 10 or 15 µCi) of iodine-125 (¹²⁵I). All the animals were killed on the sixtieth day and chromosomal aberrations were screened in spermatocytes at meiotic metaphase I. A significant increase in the percentage of chromosomal aberrations including translocations (0, 1·2, 1·8 and 2·3 per cent translocations in controls, 185, 370 and 555 kBq groups respectively) was recorded at all dose levels indicating the clatogenic effects of ¹²⁵I in mouse spermatocytes.     

Egr-IFNγ基因治疗联合125I-脱氧尿嘧啶核苷治疗抑瘤效应的实验研究

目的 探讨Egr-IFNγ基因治疗联合放射性核素 ¹²⁵I -脱氧尿嘧啶核苷治疗方案在荷H22肝癌细胞小鼠体内抑瘤效应及机制。方法 小鼠肿瘤局部注射脂质体包裹的质粒,注射后48 h,肿瘤局部注射370kBq ¹²⁵I -UdR。观察各组小鼠治疗后不同时间肿瘤生长率;治疗后第3 天,检测肿瘤胞浆蛋白中IFNγ的表达和脾脏CTL细胞毒活性。结果 基因-放射核素治疗后第6～15天,pcDNAEgr-IFNγ+ ¹²⁵I -UdR组肿瘤生长率明显低于对照组、 ¹²⁵I -UdR组及pcDNAEgr-1+ ¹²⁵I -UdR 组;基因-放射性核素治疗后第3天,pcDNAEgr-IFNγ+ ¹²⁵I -UdR组肿瘤胞浆蛋白中可检测到IFNγ的表达,其余组肿瘤胞浆蛋白中未检测到IFNγ的表达;pcDNAEgr-IFNγ+ ¹²⁵I -UdR组小鼠脾脏CTL细胞毒活性明显高于其余组 (P<0.01)。结论 pcDNAEgr-IFNγ基因治疗联合放射性核素 ¹²⁵I -UdR治疗抑瘤效应明显优于单纯 ¹²⁵I -UdR放射性核素治疗。     

Effect of Ploidy on the Response of V79 Cells to Ionizing Radiation

Summary

The responses of diploid, tetraploid and near-hexaploid V79 cells to X-irradiation or DNA-associated ¹²⁵I-decay were compared. When cell killing, following X-irradiation, was plotted against the induced level of DNA double-strand breakage (dsb) per unit length of DNA, there was no significant difference between the relationships for each cell line. This suggested that the number of X-ray-induced DNA dsb per cell required to produce a lethal lesion was proportional to ploidy. Consistent with the X-ray results, tetraploid cells required 121 ± 4 and diploid cells 60 ± 1 ¹²⁵I-decays to produce a lethal lesion. However, the hexaploid cells deviated from this relationship and required 137 ± 5 decays. The relationship between relative elution and ¹²⁵I decays/cell reflected cellular DNA content. It is concluded that current models of radiation action are unable to explain these findings satisfactorily.     

Radioiodinated 4-iodo-L-meta-tyrosine, a system L selective artificial amino acid: molecular design and transport characterization in Chinese hamster ovary cells (CHO-K1 cells)

IntroductionHigh expression of the system L amino acid transporter has been observed in clinically important tissues including tumors and the blood-brain barrier. We examined amino acid transport system L selectivity of ¹⁴C(U)-l-tyrosine (¹⁴C-Tyr), ¹²⁵I-4-iodo-l-meta-tyrosine (4-¹²⁵I-mTyr), ¹²⁵I-6-iodo-l-meta-tyrosine (6-¹²⁵I-mTyr), ¹²⁵I-3-iodo-α-methyl-l-tyrosine (¹²⁵I-IMT) and ¹²⁵I-3-iodo-l-tyrosine (3-¹²⁵I-Tyr) using Chinese hamster ovary cells (CHO-K1).MethodsCells in the exponential growth phase were incubated with 18.5 kBq of labeled amino acid in 2 mL of phosphate-buffered saline-based uptake solution and an uptake solution with/without Na⁺ at 37°C or 4°C. We examined the effects of the following compounds (1.0 mM) on transport: 2-(methylamino)isobutyric acid (a specific inhibitor of system A, in Na⁺-containing uptake solution); 2-amino-bicyclo[2,2,1]heptane-2-carboxylic acid (a specific inhibitor of system L, in Na⁺-free uptake solution); sodium azide and 2,4-dinitrophenol (NaN₃ and DNP, inhibitors of the generation of adenosine triphosphate); p-aminohippurate and tetraethylammonium (PAH and TEA, inhibitors of organic anion and cation transporters); and l- and d-isomers of natural amino acids.Results¹⁴C-Tyr exhibited affinity for systems L, A and ASC. 4-¹²⁵I-mTyr and 3-¹²⁵I-Tyr exhibited high specificity for system L, whereas 6-¹²⁵I-mTyr and ¹²⁵I-IMT exhibited affinity for both systems L and ASC. Uptake of 4-¹²⁵I-mTyr was markedly reduced by incubation at 4 °C, and was not significantly inhibited by NaN₃, DNP, PAH or TEA. The inhibition profiles of the l- and d-isomers of natural amino acids indicated that system L mediates the transport of 4-¹²⁵I-mTyr.Conclusions4-¹²⁵I-mTyr exhibited the greatest system L specificity (93.46±0.13%) of all of the tested amino acids.     

Mouse Lymphoma Cells that Undergo Interphase Death Show Markedly Increased Sensitivity to Radiation-induced DNA Double-strand Breakage as Compared with Cells that Undergo Mitotic Death

Summary

The relationship between radiation-induced DNA double-strand breakage (dsb) and reproductive death (clonogenicity) for two mouse lymphoma cell lines was compared with that for the fibroblast-like hamster cell line V79. One of the lymphoma lines (STRij-4-2.2), which undergoes rapid disintegration following cytotoxic insult, showed extreme sensitivity to γ-ray or DNA-associated ¹²⁵I decay-induced DNA dsb (7 ± 1 ¹²⁵I decays per clonogenic lethal event). Surprisingly, the other lymphoma line (WEHI-22.1), which does not undergo rapid disintegration, was also much more sensitive to DNA dsb than were V79 cells (17 ± 1 versus 61 ± 2 ¹²⁵I decays per clonogenic lethal event). Ultrastructure, DNA degradation, and flow cytometric cell cycle data suggested that both lymphoma cell lines may undergo interphase death, but that the induction of this process in WEHI-22.1 may depend upon blockage in the G₂ phase. It is concluded that there are marked differences between the radiation responses of lymphoma and fibroblast lines, that there may be different forms of radiation-induced interphase death, and that the low number of DNA dsb required to produce a clonogenic lethal event in cells undergoing interphase death could explain the radiosensitivity of organs such as ovary, testis and thymus.