Ramsahoye B H, Burnett A K, Taylor C
Department of Haematology, University of Wales College of Medicine, Heath Park, Cardiff, UK.
Blood. 1996 Mar 1;87(5):2065-70.
Recent studies using anion exclusion chromatography have suggested that uracil is misincorporated into the DNA of patients with megaloblastic anemia to levels detectable by nonradioactive methods. We have investigated the nucleotide composition of DNA from the bone marrow mononuclear cells of eight patients with cobalamin deficiency and compared this with that found in normal subjects. The median level of uracil in the megaloblastic group was 0.082 mol% of cytosine (approx. 0.02 mol% of all bases in DNA), which was similar to that found in the control group (median 0.085 mol% of cytosine) and may be attributable, at least in part, to artefactual deamination of deoxycytidine monophosphate during the DNA hydrolysis. Our findings give no support for the view that, by overwhelming the uracil N-glycosidase mechanism, the degree of uracil misincorporation in megaloblastic anemia is sufficient to increase the steady state level of uracil in the DNA by amounts detectable by nonradioactive methods. Using high performance liquid chromatography, we have also demonstrated normal levels of methylcytosine in the DNA of megaloblastic subjects.
最近使用阴离子排斥色谱法的研究表明，尿嘧啶错误掺入巨幼细胞贫血患者的DNA中，达到可通过非放射性方法检测到的水平。我们研究了8名钴胺素缺乏患者骨髓单个核细胞DNA的核苷酸组成，并将其与正常受试者的进行比较。巨幼细胞组中尿嘧啶的中位数水平为胞嘧啶的0.082摩尔%（约占DNA中所有碱基的0.02摩尔%），这与对照组（胞嘧啶中位数为0.085摩尔%）相似，这至少部分可能归因于DNA水解过程中脱氧胞苷单磷酸的人为脱氨作用。我们的研究结果不支持以下观点：即通过压倒尿嘧啶N-糖苷酶机制，巨幼细胞贫血中尿嘧啶错误掺入的程度足以使DNA中尿嘧啶的稳态水平增加到可通过非放射性方法检测到的量。使用高效液相色谱法，我们还证明了巨幼细胞受试者DNA中甲基胞嘧啶水平正常。
