Blount B C, Ames B N
Biomedical Mass Spectrometry Unit, University of New South Wales, Kensington, Australia.
Baillieres Clin Haematol. 1995 Sep;8(3):461-78. doi: 10.1016/s0950-3536(05)80216-1.
Folate deficiency significantly increases uracil content and chromosome breaks (as measured by micronucleated cells) in human leukocyte DNA. Folate supplementation reduces both the uracil content of DNA and the frequency of micronucleated cells, indicating that uracil misincorporation may play a causative role in folate deficiency-induced chromosome breaks. A calculation is presented to explain how the levels of uracil found in DNA could cause chromosome breaks. Based on this calculation, the frequency of uracil repair events that might result in double-strand DNA breaks increases by 1752-fold. These results are consistent with clinical and epidemiological evidence linking folate deficiency to DNA damage and cancer.
叶酸缺乏会显著增加人类白细胞DNA中的尿嘧啶含量和染色体断裂（通过微核细胞测量）。补充叶酸可降低DNA的尿嘧啶含量以及微核细胞的频率，这表明尿嘧啶错掺入可能在叶酸缺乏诱导的染色体断裂中起致病作用。本文进行了一项计算，以解释DNA中发现的尿嘧啶水平如何导致染色体断裂。基于该计算，可能导致双链DNA断裂的尿嘧啶修复事件频率增加了1752倍。这些结果与将叶酸缺乏与DNA损伤和癌症联系起来的临床和流行病学证据一致。
