Milne Elizabeth, Greenop Kathryn R, Ramankutty Padmaja, Miller Margaret, de Klerk Nicholas H, Armstrong Bruce K, Almond Theodora, O'Callaghan Nathan J, Fenech Michael
Telethon Kids Institute, University of Western Australia, Perth, Western Australia, Australia.
Child Health Promotion Research Centre, Edith Cowan University, Perth, Western Australia, Australia.
Mol Nutr Food Res. 2015 Oct;59(10):2057-65. doi: 10.1002/mnfr.201500110. Epub 2015 Aug 26.
Maintenance of normal cellular phenotype depends largely on accurate DNA replication and repair. DNA damage causes gene mutations and predisposes to cancer and other chronic diseases. Growing evidence indicates that nutritional factors are associated with DNA damage in adults; here, we investigate these associations in children.
We conducted a cross-sectional study among 462 healthy children 3, 6, and 9 years of age. Blood was collected and micronutrient levels were measured. The cytokinesis-block micronucleus cytome assay was used to measure chromosomal DNA damage (micronuclei, nucleoplasmic bridges, and nuclear buds) in lymphocytes. Cell apoptosis, necrosis, and the nuclear division index were also measured. Nine loci in genes involved in folate metabolism and DNA repair were genotyped. Data were analyzed using linear regression with adjustment for potential confounders. Plasma calcium was positively associated with micronuclei and necrosis, and α-tocopherol negatively associated with apoptosis, nuclear division index, and nucleoplasmic bridges; lutein was positively associated with nucleoplasmic bridges. α-tocopherol was positively associated with necrosis.
DNA damage in healthy children may be influenced by blood micronutrient levels and certain genotypes. Further investigation of associations between nutritional status and genomic integrity in children is needed to shed additional light on potential mechanisms.
正常细胞表型的维持很大程度上取决于准确的DNA复制和修复。DNA损伤会导致基因突变,并使人易患癌症和其他慢性疾病。越来越多的证据表明,营养因素与成年人的DNA损伤有关;在此,我们对儿童中的这些关联进行研究。
我们对462名3岁、6岁和9岁的健康儿童进行了一项横断面研究。采集血液并测量微量营养素水平。采用胞质分裂阻滞微核细胞分析法测量淋巴细胞中的染色体DNA损伤(微核、核质桥和核芽)。还测量了细胞凋亡、坏死和核分裂指数。对参与叶酸代谢和DNA修复的基因中的9个位点进行基因分型。使用线性回归分析数据,并对潜在混杂因素进行校正。血浆钙与微核和坏死呈正相关,α-生育酚与凋亡、核分裂指数和核质桥呈负相关;叶黄素与核质桥呈正相关。α-生育酚与坏死呈正相关。
健康儿童的DNA损伤可能受血液微量营养素水平和某些基因型的影响。需要进一步研究儿童营养状况与基因组完整性之间的关联,以进一步了解潜在机制。