Dörmer P, Sauer H, Schalhorn A, Wilmanns W
Cancer Res. 1982 Apr;42(4):1604-7.
The kinetics of erythroid and granulocytopoietic cell production were investigated during Courses 1 and 4 of high-dose methotrexate therapy with citrovorum factor rescue in a patient suffering from metastatic osteogenic sarcoma. Using the technique of quantitative 14C autoradiography, relative production rates were determined before, as well as 2, 24, 48, and 72 hr after, methotrexate infusion. There was only a minor decrease of the relative granulopoietic cell production 2 hr after methotrexate infusion followed by an overshoot reaction after 48 hr with a maximum of 3 to 4 times the pretherapeutic value. The relative erythropoietic cell production dropped to less than one-third of the pretherapeutic level during both courses and remained low during the period of postinfusion observation. The results indicate a severe and long-lasting impairment of the erythropoietic cell series, which is likely to include the committed stem cell pool. The impairment of granulocytopoiesis was much smaller and was followed quite soon by a reaction of recovery. The rate of DNA synthesis of individual cells was subnormal in all cell types investigated prior to Course 4 and was hardly affected by the methotrexate. Intracellular accumulation of methotrexate polyglutamates and differences in this pattern of accumulation between the red and white cell series are discussed as one possible explanation in this context.
在一名转移性骨肉瘤患者接受高剂量甲氨蝶呤治疗并使用亚叶酸钙解救的第1疗程和第4疗程期间，对红系和粒系造血细胞生成的动力学进行了研究。采用定量14C放射自显影技术，在甲氨蝶呤输注前以及输注后2、24、48和72小时测定相对生成率。甲氨蝶呤输注后2小时，粒系造血细胞的相对生成仅略有下降，随后在48小时出现过冲反应，最高达到治疗前值的3至4倍。在两个疗程中，红系造血细胞的相对生成均降至治疗前水平的三分之一以下，并且在输注后观察期内一直保持较低水平。结果表明红系造血细胞系列存在严重且持久的损伤，这可能包括定向干细胞池。粒系造血的损伤要小得多，并且很快就出现了恢复反应。在第4疗程之前，所有研究的细胞类型中单个细胞的DNA合成速率均低于正常水平，并且几乎不受甲氨蝶呤的影响。在这种情况下，讨论了甲氨蝶呤多聚谷氨酸盐在细胞内的积累以及红系和白系细胞系列在这种积累模式上的差异，作为一种可能的解释。
