Catala Gema Nadal, Bestwick Charles S, Russell Wendy R, Tortora Katia, Giovannelli Lisa, Moyer Mary Pat, Lendoiro Elena, Duthie Susan J
Natural Products Group, Division of Lifelong Health, Rowett Institute of Nutrition and Health, University of Aberdeen, Aberdeen, UK.
Department NEUROFARBA, Section of Pharmacology and Toxicology, University of Florence, Florence, Italy.
Mutat Res Genet Toxicol Environ Mutagen. 2019 Jul;843:73-80. doi: 10.1016/j.mrgentox.2018.08.012. Epub 2018 Sep 5.
Intake of folate (vitamin B) is strongly inversely linked with human cancer risk, particularly colon cancer. In general, people with the highest dietary intake of folate or with high blood folate levels are at a reduced risk (approx. 25%) of developing colon cancer. Folate acts in normal cellular metabolism to maintain genomic stability through the provision of nucleotides for DNA replication and DNA repair and by regulating DNA methylation and gene expression. Folate deficiency can accelerate carcinogenesis by inducing misincorporation of uracil into DNA, by increasing DNA strand breakage, by inhibiting DNA base excision repair capacity and by inducing DNA hypomethylation and consequently aberrant gene and protein expression. Conversely, increasing folate intake may improve genomic stability. This review describes key applications of single cell gel electrophoresis (the comet assay) in assessing genomic instability (misincorporated uracil, DNA single strand breakage and DNA repair capacity) in response to folate status (deficient or supplemented) in human cells in vitro, in rodent models and in human case-control and intervention studies. It highlights an adaptation of the SCGE comet assay for measuring genome-wide and gene-specific DNA methylation in human cells and colon tissue.
叶酸（维生素B）的摄入量与人类患癌风险，尤其是结肠癌风险呈强烈负相关。一般来说，叶酸膳食摄入量最高或血液中叶酸水平较高的人群患结肠癌的风险降低（约25%）。叶酸在正常细胞代谢中发挥作用，通过为DNA复制和DNA修复提供核苷酸以及调节DNA甲基化和基因表达来维持基因组稳定性。叶酸缺乏可通过诱导尿嘧啶错误掺入DNA、增加DNA链断裂、抑制DNA碱基切除修复能力以及诱导DNA低甲基化并进而导致异常的基因和蛋白质表达来加速致癌过程。相反，增加叶酸摄入量可能会改善基因组稳定性。本综述描述了单细胞凝胶电泳（彗星试验）在评估体外培养的人类细胞、啮齿动物模型以及人类病例对照和干预研究中，针对叶酸状态（缺乏或补充）所产生的基因组不稳定性（尿嘧啶错误掺入、DNA单链断裂和DNA修复能力）方面的关键应用。它强调了对SCGE彗星试验进行改进，用于测量人类细胞和结肠组织中的全基因组和基因特异性DNA甲基化。
