Tytgat G A, Voûte P A, Takeuchi S, Miyoshi I, Rutgers M
University of Amsterdam, Dept. of Radiobiology, The Netherlands.
Eur J Cancer. 1995;31A(4):603-6. doi: 10.1016/0959-8049(95)00058-q.
The major toxicity encountered with [131I]-Meta-iodobenzylguanidine (MIBG) therapy in neuroblastoma patients is an often isolated thrombocytopenia. We believe that this results from MIBG-induced radiotoxicity of the megakaryocytes. Since it is difficult to obtain enough human megakaryocytes for uptake studies, we investigated whether the megakaryocytic cell lines, MKPL-1, CHRF-288-11 and HEL, are good models to study serotonin and MIBG accumulation in human megakaryocytes. Compared with platelets, low levels of specific MIBG accumulation (imipramine-sensitive) were shown in all cell lines, but that of serotonin was negligible in MKPL-1 and CHRF-288-11. Furthermore, the proportion of specific uptake of both MIBG and serotonin appeared greatest in the HEL cells. Although these cells seem to be good candidates to study serotonin and MIBG uptake, they are not a good model to investigate MIBG and serotonin accumulation in human megakaryocytes since they have no functional storage granules.
[131I]-间碘苄胍(MIBG)治疗神经母细胞瘤患者时遇到的主要毒性通常是孤立性血小板减少。我们认为这是由MIBG诱导的巨核细胞放射毒性所致。由于难以获取足够的人类巨核细胞用于摄取研究,我们研究了巨核细胞系MKPL-1、CHRF-288-11和HEL是否是研究人类巨核细胞中5-羟色胺和MIBG积累的良好模型。与血小板相比,所有细胞系中均显示出低水平的特异性MIBG积累(对丙咪嗪敏感),但在MKPL-1和CHRF-288-11中5-羟色胺的积累可忽略不计。此外,HEL细胞中MIBG和5-羟色胺的特异性摄取比例似乎最大。尽管这些细胞似乎是研究5-羟色胺和MIBG摄取的良好候选者,但由于它们没有功能性储存颗粒,因此不是研究人类巨核细胞中MIBG和5-羟色胺积累的良好模型。