Duthie S J
Division of Micronutrients and Lipid Metabolism, Rowett Research Institute, Aberdeen, UK.
Br Med Bull. 1999;55(3):578-92. doi: 10.1258/0007142991902646.
Folic acid deficiency in humans has been linked with megaloblastic anaemia, neural tube defects in the neonate, and heart disease. Folate has also been implicated in the development of cancer, especially cancer of the colorectum. There appear to be two principal mechanisms through which low folate status may increase the risk of malignancy. Folate deficiency, by reducing intracellular S-adenosylmethionine (SAM), can alter cytosine methylation in DNA, leading to inappropriate activation of proto-oncogenes and induction of malignant transformation. Alternatively, folic acid is crucial for normal DNA synthesis and repair. Folate deficiency may cause an imbalance in DNA precursors, uracil misincorporation into DNA, and chromosome breakage. This chapter briefly describes the epidemiological data supporting the involvement of folic acid in the aetiology of cancer. It also assesses the evidence from cellular, animal and human studies that folic acid can modulate DNA by such mechanisms.
人体叶酸缺乏与巨幼细胞贫血、新生儿神经管缺陷以及心脏病有关。叶酸还与癌症的发生发展有关，尤其是结直肠癌。低叶酸状态可能通过两种主要机制增加患恶性肿瘤的风险。叶酸缺乏会通过降低细胞内S-腺苷甲硫氨酸（SAM），改变DNA中的胞嘧啶甲基化，导致原癌基因的不适当激活和恶性转化的诱导。另外，叶酸对于正常的DNA合成和修复至关重要。叶酸缺乏可能导致DNA前体失衡、尿嘧啶错误掺入DNA以及染色体断裂。本章简要描述了支持叶酸参与癌症病因学的流行病学数据。它还评估了来自细胞、动物和人体研究的证据，即叶酸可通过这些机制调节DNA。
