Dahlström Maria, Capala Jacek, Lindström Peter, Wasteson Ake, Lindström Annelie
Division of Cell Biology, Department of Biomedicine and Surgery, Faculty of Health Sciences, Linköping University, Sweden.
J Neurooncol. 2004 Jul;68(3):199-205. doi: 10.1023/b:neon.0000033489.54011.6b.
It has been shown that human malignant glioma tumours consist of several subpopulations of tumour cells. Due to heterogeneity and different degrees of vascularisation cell subpopulations possess varying resistance to chemo- or radiation therapy. Therefore, therapy is dependent on the ability to specifically target a tumour cell. Boron neutron capture therapy (BNCT) is a bimodal method, in radiation therapy, taking advantage of the ability of the stable isotope boron-10 to capture neutrons. It results in disintegration products depositing large amounts of energy within a short length, approximately one cell diameter. Thereby, selective irradiation of a target cell may be accomplished if a sufficient amount of boron has been accumulated and hence the cell-associated boron concentration is of critical importance. The accumulation of boron, boronophenylalanine (BPA), was investigated in two human glioma cell subpopulations and a human fibroblast cell line in vitro. The cells were incubated at low boron concentrations (0-5 microg B/ml). Oil filtration was then used for separation of extracellular and cell-associated boron. Inductively coupled plasma atomic emission spectroscopy (ICP-AES) was used for boron determination. Significant (P < 0.05) differences in accumulation ratio (relation between cell-associated and extracellular boron concentration) between human malignant glioma cell lines were found. Human fibroblasts, used to represent normal cells, showed a growth-dependent uptake and a lower accumulation ratio than the glioma cells. Our findings indicate that BPA concentration, incubation time and differences in boron uptake between cell subpopulations should be considered in BNCT.
研究表明,人类恶性胶质瘤肿瘤由几个肿瘤细胞亚群组成。由于肿瘤细胞的异质性和不同程度的血管化,细胞亚群对化疗或放疗具有不同的抗性。因此,治疗取决于特异性靶向肿瘤细胞的能力。硼中子俘获疗法(BNCT)是放射治疗中的一种双峰疗法,它利用稳定同位素硼 - 10俘获中子的能力。其产生的裂变产物在短距离内沉积大量能量,大约为一个细胞直径。因此,如果积累了足够量的硼,就可以实现对靶细胞的选择性照射,因此与细胞相关的硼浓度至关重要。在体外研究了硼、硼代苯丙氨酸(BPA)在两个人类胶质瘤细胞亚群和一个人类成纤维细胞系中的积累情况。细胞在低硼浓度(0 - 5微克硼/毫升)下孵育。然后使用油过滤法分离细胞外硼和与细胞相关的硼。采用电感耦合等离子体原子发射光谱法(ICP - AES)测定硼含量。发现人类恶性胶质瘤细胞系之间的积累率(细胞相关硼浓度与细胞外硼浓度的关系)存在显著(P < 0.05)差异。用于代表正常细胞的人类成纤维细胞表现出与生长相关的摄取,并且其积累率低于胶质瘤细胞。我们的研究结果表明,在BNCT中应考虑BPA浓度、孵育时间以及细胞亚群之间硼摄取的差异。