Ferguson Lynnette R, Philpott Martin
Discipline of Nutrition, Faculty of Medical and Health Sciences, The University of Auckland, New Zealand.
Annu Rev Nutr. 2008;28:313-29. doi: 10.1146/annurev.nutr.28.061807.155449.
Diet-related mutagenesis plays an etiologic role in chronic diseases, including cardiovascular disease and cancer. Many dietary mutagens are DNA reactive, leading to distinct spectra of base-pair substitution mutations and structural chromosome changes. Examples include aflatoxin B1, ochratoxin A, ptaquiloside, various pyrrolizidine alkaloids, heterocyclic amines including 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, and polycyclic aromatic hydrocarbons such as benzo[a]pyrene. However, endogenously or exogenously formed reactive species, inhibitors of topoisomerase II enzymes (e.g., flavonoids), of DNA repair (e.g., caffeine), or of the mitotic spindle (possibly acrylamide), also cause mutations, including structural chromosome changes and copy number variants. Genomic instability also results from inadequate nutrient intake (e.g., folate and selenium). Antimutagens include vitamin C, carotenoids, chlorophyllin, dietary fibers, and plant polyphenols acting through various mechanisms. Polymorphisms in genes for nutrient uptake, metabolism, and excretion will affect dietary intake in determining individual risk of disease development. Human studies utilizing nutrigenomic/nutrigenetic technologies will be essential to quantifying and overcoming diet-related mutagenesis.
与饮食相关的诱变作用在包括心血管疾病和癌症在内的慢性疾病中发挥着病因学作用。许多饮食诱变剂具有DNA反应活性，会导致不同类型的碱基对替代突变和染色体结构变化。例子包括黄曲霉毒素B1、赭曲霉毒素A、ptaquiloside、各种吡咯里西啶生物碱、包括2-氨基-1-甲基-6-苯基咪唑并[4,5-b]吡啶在内的杂环胺，以及多环芳烃如苯并[a]芘。然而，内源性或外源性形成的活性物质、拓扑异构酶II酶的抑制剂（如黄酮类化合物）、DNA修复的抑制剂（如咖啡因）或有丝分裂纺锤体的抑制剂（可能是丙烯酰胺）也会导致突变，包括染色体结构变化和拷贝数变异。营养摄入不足（如叶酸和硒）也会导致基因组不稳定。抗诱变剂包括维生素C、类胡萝卜素、叶绿酸、膳食纤维和通过各种机制发挥作用的植物多酚。营养吸收、代谢和排泄相关基因的多态性会在决定个体疾病发生风险时影响饮食摄入。利用营养基因组学/营养遗传学技术的人体研究对于量化和克服与饮食相关的诱变作用至关重要。
