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氚标记化合物在医学领域中被广泛应用,如3H标记的胸腺嘧啶核苷(3H-thymidine, 3H-TdR)在淋巴细胞辐射效应中生物大分子损伤的早期研究[1]、H3标记的生物大分子用于研究物质在体内的代谢、扩散、交换等。此外,氚还被用于标记放射性化合物,追踪某些生物分子的行踪和代谢,以及新药的药物代谢与药物动力学的研究[2]。通过上述方法能获取药物在生物体内的代谢动力学参数,测量生物吸收利用度、器官与组织分布,计算排泄的速度与途径等数据资料,因此氚在新药研发过程中发挥着重要作用。应用氚标记方法还可以检测机体免疫功能,观察辐射后的生物效应和药物治疗后的疗效等[3-4]。
氚标记化合物在放射生物学基础与应用中的研究进展
Research progress of tritium-labeled compounds in the basis and application of radiobiology
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摘要: 氚标记化合物被广泛应用于医学领域,特别是氚标记的生物大分子可用于分析生物体内与细胞内各类分子的代谢过程。笔者介绍了氚标记化合物的合成方法,概述了氚标记的生物大分子在放射生物学基础研究与医学应用中的成果及研究进展,重点阐述了氚标记的胸腺嘧啶核苷在测定DNA合成效率中的原理与应用。氚标记化合物对于研究细胞内DNA、RNA、蛋白质等分子的分布、代谢过程具有简便、迅速、直观、准确的优点,进一步研发基于氚标记化合物的分析方法对于深入认识分子生物学机制具有重要意义。Abstract: Tritium-labeled compounds are widely used in the field of medicine, especially tritium-labeled biomolecules, which can be used to analyze the metabolic processes of various molecules inside and within cells. This article introduces the synthesis methods of tritium-labeled compounds, provides an overview of the achievements and research progress of tritium-labeled biomolecules in the field of radiobiology and medical applications, with a focus on explaining the principles and applications of tritium-labeled thymidine nucleosides in determining DNA synthesis efficiency. Tritium-labeled compounds offer the advantages of simplicity, speed, intuitiveness, and accuracy in studying the distribution and metabolic processes of molecules such as DNA, RNA, and proteins within cells. Further development of analytical methods based on tritium-labeled compounds is of significant importance for a deeper understanding of molecular biology mechanisms.
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Key words:
- Radioisotope /
- Tritium-labeled compounds /
- DNA synthesis /
- Radiation biological effects
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[1] 苏燎原. 淋巴细胞及其辐射效应[M]. 2版. 北京: 原子能出版社, 2013: 69−70.
Su LY. Lymphocyte and its irradiation effect[M]. 2nd ed. Beijing: Atomic Energy Press, 2013: 69−70.[2] Pony Yu R, Hesk D, Rivera N, et al. Iron-catalysed tritiation of pharmaceuticals[J]. Nature, 2016, 529(7585): 195−199. DOI: 10.1038/nature16464. [3] 刘芬菊, 苏燎原, 刘克良, 等. 冻结肩病人的免疫功能测定[J]. 苏州医学院学报, 1992, 12(1): 56−57, 73.
Liu FJ, Su LY, Liu KL, et al. Determination on the frozen shoulder patients' immunolic function[J]. Acta Acad Med Suzhou, 1992, 12(1): 56−57, 73.[4] 刘芬菊, 苏燎原. 维生素A对CD4+和CD8+细胞辐射效应的影响[J]. 辐射研究与辐射工艺学报, 1995, 13(1): 29−32.
Liu FJ, Su LY. The effect of vitamin A on CD4+ and CD8+ cells irradiated by 60Co γ-ray[J]. J Radiat Res Radiat Process, 1995, 13(1): 29−32.[5] Atzrodt J, Derdau V, Kerr WJ, et al. Deuterium- and tritium-labelled compounds: applications in the life sciences[J]. Angew Chem Int Ed Engl, 2018, 57(7): 1758−1784. DOI: 10.1002/anie.201704146. [6] 林奋智, 沈德福. 高比度氚标记腺嘌呤核苷三磷酸的制备[J]. 核技术, 1980, 2: 52−54.
Lin FZ, Shen DF. Preparation of high specific activity tritium-labelled adenosine-5-triphosphate[J]. Nucl Tech, 1980, 2: 52−54.[7] Chernysheva MG, Badun GA, Kulikova NA, et al. Behavior of humic substances in the liquid-liquid system directly measured using tritium label[J]. Chemosphere, 2020, 238: 124646. DOI: 10.1016/j.chemosphere.2019.124646. [8] 苏燎原, 黄汉贤, 岑建农. 应用DNA损伤与修复测定法研究肿瘤细胞的放射敏感性[J]. 肿瘤防治研究, 1997, 24(6): 337−339.
Su LY, Huang HX, Cen JN. The studies of radiation sensitivity of tumor cells by using determinating method of DNA damage and repair[J]. Cancer Res Prev Treat, 1997, 24(6): 337−339.[9] 刘克良, 苏燎原, 刘芬菊, 等. PHA、ConA、PWM对血内淋巴细胞的激活效应研究[J]. 苏州医学院学报, 1986, 6(3): 20−23.
Liu KL, Su LY, Liu FJ, et al. The study of stimulating effect of PHA, ConA and PWM on lymphocytes on human blood[J]. Acta Acad Med Suzhou, 1986, 6(3): 20−23.[10] 杜泽吉, 苏燎原. FADU法研究低剂量辐射对淋巴细胞DNA断裂及修复的影响[J]. 苏州医学院学报, 1995, 15(3): 613−615, 799.
Du ZJ, Su LY. Effects of low dose irradiation on DNA strand breaks and its repair in lymphocytes[J]. Acta Acad Med Suzhou, 1995, 15(3): 613−615, 799.[11] Maeno K, Nakajima A, Conseil G, et al. Molecular basis for reduced estrone sulfate transport and altered modulator sensitivity of transmembrane helix (TM) 6 and TM17 mutants of multidrug resistance protein 1 (ABCC1)[J]. Drug Metab Dispos, 2009, 37(7): 1411−1420. DOI: 10.1124/dmd.109.026633. [12] 张建华, 苏燎原, 盛锦云, 等. 儿童T-淋巴细胞DNA、蛋白质合成及低剂量辐射效应的研究[J]. 中国实用儿科杂志, 2000, 15(2): 88−90. DOI: 10.3969/j.issn.1005-2224.2000.02.011.
Zhang JH, Su LY, Sheng JY, et al. Study on synthesis of DNA and protein of T-lymphocyte in children and effect of low dose radiation[J]. Chin J Pract Pediatr, 2000, 15(2): 88−90. DOI: 10.3969/j.issn.1005-2224.2000.02.011.[13] Wang LF, Hong HZ, Zhang DL. Applications of quantitative whole-body autoradiography (QWBA) in drug discovery and development[M]//Zhang DL, Surapaneni S. ADME-Enabling technologies in drug design and development. Hoboken: John Wiley & Sons, Inc., 2012: 419. [14] Jakubczyk D, Brenner-Weiss G, Bräse S. Synthesis of tritium labelled and photoactivatable N-acyl-l-homoserine lactones: inter-kingdom signalling molecules[J]. Eur J Org Chem, 2014, 2014(3): 592−597. DOI: 10.1002/ejoc.201300800. [15] Usui T, Mise M, Hashizume T, et al. Evaluation of the potential for drug-induced liver injury based on in vitro covalent binding to human liver proteins[J]. Drug Metab Dispos, 2009, 37(12): 2383−2392. DOI: 10.1124/dmd.109.028860. [16] Edelmann MR. Radiolabelling small and biomolecules for tracking and monitoring[J/OL]. RSC Adv, 2022, 12(50): 32383−32400[2022-09-12]. https://dmd.aspetjournals.org/content/33/10/1418. DOI: 10.1039/d2ra06236d. [17] Jigorel E, Le Vee M, Boursier-Neyret C, et al. Functional expression of sinusoidal drug transporters in primary human and rat hepatocytes[J]. Drug Metab Dispos, 2005, 33(10): 1418−1422. DOI: 10.1124/dmd.105.004762. [18] Loh YY, Nagao K, Hoover AJ, et al. Photoredox-catalyzed deuteration and tritiation of pharmaceutical compounds[J]. Science, 2017, 358(6367): 1182−1187. DOI: 10.1126/science.aap9674. [19] Harder D, Fotiadis D. Measuring substrate binding and affinity of purified membrane transport proteins using the scintillation proximity assay[J]. Nat Protoc, 2012, 7(9): 1569−1578. DOI: 10.1038/nprot.2012.090. [20] Yang HF, Dormer PG, Rivera NR, er al. Palladium(Ⅱ)-mediated C-H tritiation of complex pharmaceuticals[J]. Angew Chem Int Ed Engl, 2018, 57(7): 1883−1887. DOI: 10.1002/anie.201711364. [21] Shen TY, Chernysheva MG, Badun GA, et al. Levofloxacin and amikacin adsorption on nanodiamonds: mechanism and application prospects[J]. Colloids Interfaces, 2022, 6(2): 35. DOI: 10.3390/colloids6020035. [22] Kopf S, Bourriquen F, Li W, et al. Recent developments for the deuterium and tritium labeling of organic molecules[J]. Chem Rev, 2022, 122(6): 6634−6718. DOI: 10.1021/acs.chemrev.1c00795. [23] 刘芬菊, 苏燎原, 刘克良. 维生素A对淋巴细胞增殖效应的影响[J]. 营养学报, 2001, 23(3): 239−241. DOI: 10.3321/j.issn:0512-7955.2001.03.013.
Liu FJ, Su LY, Liu KL. Effects of vitamin A on PHA-and LPS-activated lymphocytes proliferation[J]. Acta Nutri Sin, 2001, 23(3): 239−241. DOI: 10.3321/j.issn:0512-7955.2001.03.013.[24] 施宇佳, 潘晓松, 姚怡敏, 等. 低剂量X射线诱导NK细胞增殖治疗白血病裸鼠的实验研究[J]. 中华放射医学与防护杂志, 2011, 31(1): 17−20. DOI: 10.3760/cma.j.issn.0254-5098.2011.01.005.
Shi YJ, Pan XS, Yao YM, et al. Study on therapy of leukemia through proliferated NK cell induced by low-dose radiation in nude mice[J]. Chin J Radiol Med Prot, 2011, 31(1): 17−20. DOI: 10.3760/cma.j.issn.0254-5098.2011.01.005.
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