Fenech M
CSIRO Health Sciences and Nutrition, PO Box 10041, Gouger Street, BC, SA, 5000, Adelaide, Australia.
Food Chem Toxicol. 2002 Aug;40(8):1113-7. doi: 10.1016/s0278-6915(02)00028-5.
Diet as a key factor in determining genomic stability is more important than previously imagined because we now know that it impacts on all relevant pathways, namely exposure to dietary carcinogens, activation/detoxification of carcinogens, DNA repair, DNA synthesis and apoptosis. Current recommended dietary allowances for vitamins and minerals are based largely on the prevention of diseases of deficiency such as scurvy in the case of vitamin C. Because diseases of development, degenerative disease and aging itself are partly caused by damage to DNA it seems logical that we should focus better our attention on defining optimal requirements of key minerals and vitamins for preventing damage to both nuclear and mitochondrial DNA. To date, our knowledge on optimal micronutrient levels for genomic stability is scanty and disorganised. However, there is already sufficient evidence to suggest that marginal deficiencies in folate, vitamin B12, niacin and zinc impact significantly on spontaneous chromosome damage rate. The recent data for folate and vitamin B12 in humans with respect to micronucleus formation in blood and epithelial cells provide compelling evidence of the important role of these micronutrients in maintenance of genome integrity and the need to revise current RDAs for these micronutrients based on minimisation of DNA damage. Appropriately designed in vitro studies and in vivo placebo controlled trials with dose responses using a complementary array of DNA damage biomarkers are required to define recommended dietary allowances for genomic stability. Furthermore these studies would have to be targeted to individuals with common genetic polymorphisms that alter the bioavailability of specific micronutrients and the affinity of specific key enzymes involved in DNA metabolism for their micronutrient co-factor. That there is a need for an international collaborative effort to establish RDAs for genomic stability is self-evident.
饮食作为决定基因组稳定性的关键因素，其重要性比我们之前想象的更高，因为我们现在知道它会影响所有相关途径，即接触膳食致癌物、致癌物的激活/解毒、DNA修复、DNA合成和细胞凋亡。目前推荐的维生素和矿物质膳食摄入量主要基于预防诸如坏血病（如维生素C缺乏症）等营养缺乏疾病。由于发育疾病、退行性疾病和衰老本身部分是由DNA损伤引起的，因此我们似乎有必要更好地关注确定关键矿物质和维生素的最佳需求量，以预防核DNA和线粒体DNA的损伤。迄今为止，我们关于基因组稳定性的最佳微量营养素水平的知识既稀少又杂乱。然而，已经有足够的证据表明，叶酸、维生素B12、烟酸和锌的边缘性缺乏会显著影响自发染色体损伤率。最近关于人类叶酸和维生素B12对血液和上皮细胞微核形成影响的数据，有力地证明了这些微量营养素在维持基因组完整性方面的重要作用，以及基于最小化DNA损伤来修订这些微量营养素当前推荐膳食摄入量的必要性。需要进行适当设计的体外研究以及使用一系列互补的DNA损伤生物标志物进行剂量反应的体内安慰剂对照试验，以确定基因组稳定性的推荐膳食摄入量。此外，这些研究必须针对具有常见基因多态性的个体，这些多态性会改变特定微量营养素的生物利用度以及参与DNA代谢的特定关键酶对其微量营养素辅因子的亲和力。显然，需要开展国际合作努力来建立基因组稳定性方面的推荐膳食摄入量标准。
