Fenech Michael
Genome Health Nutrigenomics Laboratory, CSIRO Health Sciences and Nutrition, Cooperative Research Centre for Diagnostics, PO Box 10041, Adelaide BC, SA 5000, Australia.
Mutagenesis. 2005 Jul;20(4):255-69. doi: 10.1093/mutage/gei040. Epub 2005 Jun 14.
The evidence of a direct link between increased genome/epigenome damage and elevated risk for adverse health outcomes during the various stages of life, such as infertility, foetal development and cancer is becoming increasingly stronger. The latter is briefly reviewed against a background of evidence indicating that genome and epigenome damage biomarkers, in the absence of overt exposure of genotoxins, are themselves sensitive indicators of deficiency in micronutrients required as cofactors or as components of DNA repair enzymes, for maintenance methylation of CpG sequences and prevention of DNA oxidation and/or uracil incorporation into DNA. The latter is illustrated with cross-sectional and dietary intervention data obtained using the micronucleus assay and other efficient biomarkers for diagnosing genome and/or epigenome instability. The concept of recommended dietary allowances for genome stability and how this could be achieved is discussed. The 'Genome Health Nutrigenomics' concept is also introduced to define and focus attention on the specialized research area of how diet impacts on genome stability and how genotype determines nutritional requirements for genome health maintenance. The review concludes with a vision for a paradigm shift in disease prevention strategy based on the diagnosis and nutritional treatment of genome/epigenome damage on an individual basis, i.e. The Genome Health Clinic.
在生命的各个阶段,如不孕、胎儿发育和癌症,基因组/表观基因组损伤增加与不良健康后果风险升高之间存在直接联系的证据越来越确凿。本文在相关证据的背景下简要回顾了后者,这些证据表明,在没有明显接触基因毒素的情况下,基因组和表观基因组损伤生物标志物本身就是某些微量营养素缺乏的敏感指标,这些微量营养素是作为辅助因子或DNA修复酶的组成成分所必需的,用于维持CpG序列的甲基化以及防止DNA氧化和/或尿嘧啶掺入DNA。文中用通过微核试验和其他用于诊断基因组和/或表观基因组不稳定性的有效生物标志物获得的横断面和饮食干预数据对此进行了说明。文中还讨论了基因组稳定性推荐膳食摄入量的概念以及如何实现这一目标。此外,还引入了“基因组健康营养基因组学”的概念,以定义并聚焦于饮食如何影响基因组稳定性以及基因型如何决定维持基因组健康所需的营养需求这一专门研究领域。本文综述最后展望了基于对个体基因组/表观基因组损伤进行诊断和营养治疗的疾病预防策略范式转变,即基因组健康诊所。