Van Der Weyden M B
Scand J Haematol. 1979 Jul;23(1):37-42. doi: 10.1111/j.1600-0609.1979.tb02851.x.
Despite the clinical use of the 'deoxyuridine suppression test' to document vitamin B12 or folate deficiency its biochemical basis is unclear and currently disputed. Because of this the metabolism of deoxyuridine in marrow cells has been examined. In normoblastic marrow cells the ratio of radio-labelled deoxyuridine to thymidine incorporation into DNA approximates one and preincubation of cells with unlabelled deoxyuridine results in progressive reduction of uptake of both radio-labelled deoxynucleosides. In the same cells methotrexate significantly reduces the DNA incorporation of deoxyuridine but not that of thymidine. In megaloblastic marrow the ratio of radio-labelled deoxyuridine to thymidine uptake is less than one and the reduced deoxyuridine uptake is not significantly altered by either cyanocobalamin or folic acid. With megaloblastic samples the reduction by deoxyuridine of radio-labelled deoxyuridine uptake is less marked than that observed with normoblastic cells and to achieve similar results requires folic acid. These findings suggest that reduced deoxyuridylate conversion to deoxythymidylate by thymidylate synthetase is appropriate to explain the 'deoxyuridine suppression test' in megaloblastic marrow cells and that altered substrate requirements for this activity may occur in megaloblastic cells.
尽管临床上使用“脱氧尿苷抑制试验”来证明维生素B12或叶酸缺乏，但其生化基础尚不清楚且目前存在争议。因此，已对骨髓细胞中脱氧尿苷的代谢进行了研究。在正常成红细胞性骨髓细胞中，放射性标记的脱氧尿苷与胸苷掺入DNA的比例约为1，用未标记的脱氧尿苷对细胞进行预孵育会导致两种放射性标记的脱氧核苷摄取逐渐减少。在相同细胞中，甲氨蝶呤显著降低脱氧尿苷的DNA掺入，但不降低胸苷的掺入。在巨幼细胞性骨髓中，放射性标记的脱氧尿苷与胸苷摄取的比例小于1，脱氧尿苷摄取的减少不受氰钴胺或叶酸的显著影响。对于巨幼细胞性样本，脱氧尿苷对放射性标记的脱氧尿苷摄取的减少不如在正常成红细胞性细胞中观察到的明显，并且要获得相似结果需要叶酸。这些发现表明，胸苷酸合成酶将脱氧尿苷酸转化为脱氧胸苷酸的减少适合解释巨幼细胞性骨髓细胞中的“脱氧尿苷抑制试验”，并且这种活性的底物需求改变可能发生在巨幼细胞中。
