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基因因素和饮食因素都是造成个体间DNA损伤水平和DNA修复能力差异的原因。

Both genetic and dietary factors underlie individual differences in DNA damage levels and DNA repair capacity.

作者信息

Slyskova Jana, Lorenzo Yolanda, Karlsen Anette, Carlsen Monica H, Novosadova Vendula, Blomhoff Rune, Vodicka Pavel, Collins Andrew R

机构信息

Department of Molecular Biology of Cancer, Institute of Experimental Medicine ASCR, Prague, Czech Republic; Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Prague, Czech Republic.

Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway.

出版信息

DNA Repair (Amst). 2014 Apr;16:66-73. doi: 10.1016/j.dnarep.2014.01.016. Epub 2014 Mar 6.

Abstract

The interplay between dietary habits and individual genetic make-up is assumed to influence risk of cancer, via modulation of DNA integrity. Our aim was to characterize internal and external factors that underlie inter-individual variability in DNA damage and repair and to identify dietary habits beneficial for maintaining DNA integrity. Habitual diet was estimated in 340 healthy individuals using a food frequency questionnaire and biomarkers of antioxidant status were quantified in fasting blood samples. Markers of DNA integrity were represented by DNA strand breaks, oxidized purines, oxidized pyrimidines and a sum of all three as total DNA damage. DNA repair was characterized by genetic variants and functional activities of base and nucleotide excision repair pathways. Sex, fruit-based food consumption and XPG genotype were factors significantly associated with the level of DNA damage. DNA damage was higher in women (p=0.035). Fruit consumption was negatively associated with the number of all measured DNA lesions, and this effect was mediated mostly by β-cryptoxanthin and β-tocopherol (p<0.05). XPG 1104His homozygotes appeared more vulnerable to DNA damage accumulation (p=0.001). Sex and individual antioxidants were also associated with DNA repair capacity; both the base and nucleotide excision repairs were lower in women and the latter increased with higher plasma levels of ascorbic acid and α-carotene (p<0.05). We have determined genetic and dietary factors that modulate DNA integrity. We propose that the positive health effect of fruit intake is partially mediated via DNA damage suppression and a simultaneous increase in DNA repair capacity.

摘要

饮食习惯与个体基因组成之间的相互作用被认为会通过调节DNA完整性来影响癌症风险。我们的目标是确定DNA损伤和修复个体间差异背后的内部和外部因素,并确定有助于维持DNA完整性的饮食习惯。使用食物频率问卷对340名健康个体的日常饮食进行评估,并对空腹血样中的抗氧化状态生物标志物进行定量分析。DNA完整性的标志物由DNA链断裂、氧化嘌呤、氧化嘧啶以及这三者的总和作为总DNA损伤来表示。DNA修复通过碱基和核苷酸切除修复途径的基因变异和功能活性来表征。性别、水果类食物的摄入量和XPG基因型是与DNA损伤水平显著相关的因素。女性的DNA损伤更高(p = 0.035)。水果摄入量与所有测量的DNA损伤数量呈负相关,这种影响主要由β-隐黄质和β-生育酚介导(p < 0.05)。XPG 1104His纯合子似乎更容易积累DNA损伤(p = 0.001)。性别和个体抗氧化剂也与DNA修复能力有关;女性的碱基切除修复和核苷酸切除修复均较低,后者随着血浆中抗坏血酸和α-胡萝卜素水平的升高而增加(p < 0.05)。我们已经确定了调节DNA完整性的遗传和饮食因素。我们提出,水果摄入对健康的积极影响部分是通过抑制DNA损伤和同时提高DNA修复能力来介导的。

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