Teo Theodora, Fenech Michael
CSIRO Human Nutrition, P.O. Box 10041, Adelaide BC, South Australia 5000, Australia.
Mutat Res. 2008 Nov 17;657(1):32-8. doi: 10.1016/j.mrgentox.2008.08.002. Epub 2008 Aug 12.
Chromosomal mutations are commonly found in cancer cells, and can be caused by several factors including dietary insufficiency and exposure to environmental and life-style genotoxins. Folate (vitamin B9), one of the essential micronutrients, is required for DNA repair and synthesis and to maintain genome stability. Since excessive alcohol (ethanol) consumption may alter folate status and low folate might alter susceptibility to alcohol toxicity, a study was performed to investigate the individual and interactive impacts of folic acid (FA) and ethanol on genome stability in vitro. The experiments were performed using WIL2-NS cells cross-tested at three FA (20, 200 and 2000 nM) and four ethanol concentrations (0, 0.09, 0.36 and 1.34%, v/v) over a two-week culture time. Chromosomal damage and cytotoxicity were measured using the cytokinesis-block micronucleus cytome assay. The present study showed dose-related genotoxic effects of both decreasing folic acid concentration and increased ethanol on day 15 resulting in significant induction of micronuclei, nuclear buds and nucleoplasmic bridges which are biomarkers of chromosome breakage or loss, gene amplification and chromosomal rearrangement, respectively. Increased ethanol and FA deficiency interacted to further significantly increase micronuclei and nucleoplasmic bridges. However there was no evidence showing alcohol's ability to cleave FA. The findings from this study suggest a protective effect of FA against alcohol-induced DNA damage and that FA deficiency in the physiological range has a stronger impact on genome stability than exposure to cytotoxic doses of ethanol achievable in binge drinking.
染色体突变在癌细胞中很常见，可能由多种因素引起，包括饮食不足以及接触环境和生活方式中的基因毒素。叶酸（维生素B9）是一种必需的微量营养素，对DNA修复和合成以及维持基因组稳定性至关重要。由于过量饮酒（乙醇）可能会改变叶酸状态，而低叶酸水平可能会改变对酒精毒性的易感性，因此进行了一项研究，以调查叶酸（FA）和乙醇对体外基因组稳定性的单独和交互影响。实验使用WIL2-NS细胞进行，在两周的培养时间内，对三种叶酸浓度（20、200和2000 nM）和四种乙醇浓度（0、0.09、0.36和1.34%，v/v）进行交叉测试。使用胞质分裂阻滞微核细胞分析法测量染色体损伤和细胞毒性。本研究表明，在第15天，叶酸浓度降低和乙醇浓度增加均具有剂量相关的遗传毒性作用，导致微核、核芽和核质桥的显著诱导，它们分别是染色体断裂或丢失、基因扩增和染色体重排的生物标志物。乙醇增加和叶酸缺乏相互作用，进一步显著增加微核和核质桥。然而，没有证据表明酒精有裂解叶酸的能力。本研究结果表明叶酸对酒精诱导的DNA损伤具有保护作用，并且在生理范围内叶酸缺乏对基因组稳定性的影响比暴饮中可达到的细胞毒性剂量的乙醇暴露更强。
