Shigematsu Akiyo, Yui Joji, Hamai Yuko, Hatori Akiko
Institute of Whole Body Metabolism, Nauchi, Shiroi City, Chiba, Japan.
Eur J Drug Metab Pharmacokinet. 2005 Jan-Jun;30(1-2):29-39. doi: 10.1007/BF03226405.
A novel autoradiographic procedure was developed for such continuously cycling cells as stem cells on account of proliferating rate of which is astronomically high per min. Negative visualization is observed over any mitotic image by use of a biomarker, "[2-14C]thymidine" for a few minutes in both cases, either in vivo or in vitro systems. But, good visualization images were realized by many 14C-beta tracks over stem cells with a few minute labelling of [2-14C]thymidine in originated cradles as predicted by Burkitt, H.G(1993). It is clearly elucidated that a short and quick labelling procedure of [2-14C]thymidine is useful to evaluate toxicity and efficacy of new drug candidates and to diagnose cluster of unknown malignity or proliferation rate of respective stem cell in in vivo or Ex-vivo system. Results show that the cell proliferation rate of the stem cells in respective tissues was markedly suppressed, dependent on time after dosing and the dose of 90Y; 3.7, 37, 370, 3,700, and 37,000 kBq per mouse (25g). In addition to the above, the sensitivity of the proliferation rate was dependent on amitosis or mitosis and the AUC value of 90Y-concentration at specific locations of the cells in the mouse body. The most sensitive cells were the plasmacytoma cells, followed by the pluripotent and unipotent stem cells, the intestinal crypts, epiphysial growth plate and liver cells. Results in this presentation, also gives a clear evidence showing a revival of facultative divider line from G0 stage of epithelium and mascular meditate into the unipotent stem cell cycle. Application of [2-14C]thymidine is useful for evaluation of a grade of maturation in differentiation of malignant cells or replicable unipotent stem cells.
由于干细胞等连续循环细胞每分钟的增殖速率极高，因此开发了一种新的放射自显影程序。在体内或体外系统中，使用生物标志物“[2-14C]胸苷”，在几分钟内，任何有丝分裂图像上都会观察到负显影。但是，正如伯基特（Burkitt，H.G，1993年）所预测的那样，通过在起源的摇篮中用[2-14C]胸苷进行几分钟的标记，干细胞上有许多14C-β径迹，从而实现了良好的显影图像。显然，[2-14C]胸苷的短时间快速标记程序可用于评估新候选药物的毒性和疗效，以及诊断体内或离体系统中未知恶性肿瘤的聚集或各个干细胞的增殖速率。结果表明，给药后不同时间以及90Y剂量（每只25g小鼠3.7、37、370、3700和37000kBq）下，各组织中干细胞的细胞增殖速率均受到明显抑制。除此之外，增殖速率的敏感性取决于无丝分裂或有丝分裂以及小鼠体内细胞特定位置的90Y浓度的AUC值。最敏感的细胞是浆细胞瘤细胞，其次是多能和单能干细胞、肠隐窝、骨骺生长板和肝细胞。本报告中的结果也清楚地证明了上皮细胞和肌肉细胞从G0期恢复到兼性分裂系并进入单能干细胞周期。[2-14C]胸苷的应用有助于评估恶性细胞或可复制单能干细胞分化的成熟程度。
