Pettersson O A, Olsson P, Lindström P, Sjöberg S, Larsson B S, Carlsson J
Department of Radiation Sciences, Uppsala University, Sweden.
Acta Oncol. 1994;33(6):685-91. doi: 10.3109/02841869409121783.
The boron containing substances L- and D-carboranylalanine might be of interest for boron neutron capture therapy, BNCT. Cultured mouse melanoma B16 cells were analyzed regarding binding of these substances and some introductory studies on effects of thermal neutron irradiation were also carried out. Comparisons were made with two boron containing compounds, p-boronophenylalanine (BPA) and boronated thiouracil (BTU-1), previously proposed for BNCT of melanomas. The results showed that both L- and D-carboranylalanine bound well in the B16 cells whereas BTU-1 gave no, and BPA only a low, binding. Thus, both forms of carboranes bound better than the two previously proposed substances. The carboranes also bound rather well in two tested human melanoma cell lines, IGR1 and RPMI-7951. Both L- and D-carboranylalanine showed a certain binding to isolated melanin but were not incorporated during melanin synthesis. Cultured glioma cells, used for comparison, bound BPA and to some extent the carboranes. This indicates that the substances are not melanoma specific. The carboranes caused some acute detachment of monolayer growing cells but were not strongly toxic since they did not reduce the growth rate. The cells treated with L-carboranylalanine or BPA showed, after neutron irradiation, a clear decrease in survival compared to the controls whereas no or only small effects were seen for cells treated with D-carboranylalanine or BTU-1. These results were conflicting since BPA gave therapeutical effects although only small amounts were bound while D-carboranylalanine gave no significant therapeutical effect in spite of better binding. One explanation might be different intracellular localizations. This has to be studied in more detail.
含硼物质L-和D-碳硼烷丙氨酸可能对硼中子俘获疗法（BNCT）具有重要意义。针对这些物质的结合情况，对培养的小鼠黑色素瘤B16细胞进行了分析，并开展了一些关于热中子辐照效应的初步研究。将其与两种先前被提议用于黑色素瘤BNCT的含硼化合物——对硼苯丙氨酸（BPA）和硼化硫脲（BTU-1）进行了比较。结果显示，L-和D-碳硼烷丙氨酸在B16细胞中均能良好结合，而BTU-1未表现出结合，BPA仅表现出低结合率。因此，两种形式的碳硼烷结合情况均优于先前提出的两种物质。碳硼烷在两种测试的人类黑色素瘤细胞系IGR1和RPMI-7951中也表现出较好的结合。L-和D-碳硼烷丙氨酸均与分离出的黑色素有一定结合，但在黑色素合成过程中未被掺入。作为对照的培养神经胶质瘤细胞能结合BPA，在一定程度上也能结合碳硼烷。这表明这些物质并非黑色素瘤特异性的。碳硼烷导致单层生长细胞出现一定程度的急性脱离，但毒性不强，因为它们并未降低细胞生长速率。与对照组相比，经中子辐照后，用L-碳硼烷丙氨酸或BPA处理的细胞存活率明显下降，而用D-碳硼烷丙氨酸或BTU-1处理的细胞未出现或仅出现微小影响。这些结果相互矛盾，因为尽管BPA结合量很少却产生了治疗效果，而D-碳硼烷丙氨酸尽管结合效果更好却未产生显著治疗效果。一种解释可能是细胞内定位不同。这还有待更详细的研究。
