Jayaram H N, Pillwein K, Nichols C R, Hoffman R, Weber G
Biochem Pharmacol. 1986 Jun 15;35(12):2029-32. doi: 10.1016/0006-2952(86)90737-9.
This study reports the selective sensitivity to tiazofurin (2-beta-D-ribofuranosylthiazole-4-carboxamide, NSC-286193) of human leukemic leukocytes as compared to normal ones in bone marrow and peripheral blood samples by comparing the production of the active metabolite, thiazole-4-carboxamide adenine dinucleotide (TAD), from labeled tiazofurin and the depression of GTP concentration. When labeled tiazofurin was incubated with leukocytes obtained from healthy volunteers or from leukemic patients (acute non-lymphocytic leukemia or acute lymphoblastic leukemia), the TAD production was 27.0 +/- 8.3, 551.3 +/- 71.8 and 755.9 +/- 94.1 pmoles/10(9) cells per hr, respectively. Thus, the leukemic cells produced over 20-fold higher concentrations of TAD than the normal leukocytes. Incubation with tiazofurin in leukemic leukocytes decreased the GTP pools (to 48-79%), whereas there was no change in the normal leukocytes. These results indicate a selectivity of response to tiazofurin in human normal and leukemic leukocytes. The procedure reported in this work may be suitable as a rapid predictive test for the sensitivity of leukemic leukocytes to tiazofurin. Such a diagnostic test should be helpful in identifying neoplastic cells sensitive to tiazofurin in the Phase II trials now being developed.
本研究通过比较标记的替加氟林产生的活性代谢物噻唑 - 4 - 甲酰胺腺嘌呤二核苷酸（TAD）的生成量以及GTP浓度的降低情况，报告了人白血病白细胞与骨髓和外周血样本中的正常白细胞相比，对替加氟林（2 - β - D - 呋喃核糖基噻唑 - 4 - 甲酰胺，NSC - 286193）的选择性敏感性。当将标记的替加氟林与从健康志愿者或白血病患者（急性非淋巴细胞白血病或急性淋巴细胞白血病）获得的白细胞一起孵育时，TAD的生成量分别为每小时27.0±8.3、551.3±71.8和755.9±94.1皮摩尔/10⁹个细胞。因此，白血病细胞产生的TAD浓度比正常白细胞高20倍以上。在白血病白细胞中用替加氟林孵育会使GTP池减少（降至48 - 79%），而正常白细胞中则没有变化。这些结果表明人正常白细胞和白血病白细胞对替加氟林的反应具有选择性。本研究报告的方法可能适合作为白血病白细胞对替加氟林敏感性的快速预测试验。这样一种诊断试验在目前正在开展的II期试验中，对于识别对替加氟林敏感的肿瘤细胞应该是有帮助的。
