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

被引:41
作者
Slyskova, Jana [1 ,2 ]
Lorenzo, Yolanda [3 ]
Karlsen, Anette [3 ]
Carlsen, Monica H. [3 ]
Novosadova, Vendula [4 ]
Blomhoff, Rune [3 ,5 ]
Vodicka, Pavel [1 ,2 ]
Collins, Andrew R. [3 ]
机构
[1] ASCR, Inst Expt Med, Dept Mol Biol Canc, Prague, Czech Republic
[2] Charles Univ Prague, Fac Med 1, Inst Biol & Med Genet, Prague, Czech Republic
[3] Univ Oslo, Fac Med, Inst Basic Med Sci, Dept Nutr, N-0316 Oslo, Norway
[4] Inst Biotechnol ASCR, Dept Gene Express, Prague, Czech Republic
[5] Oslo Univ Hosp, Div Canc Med Surg & Transplantat, Oslo, Norway
关键词
DNA damage; DNA repair capacity; Diet; Genetic polymorphisms; Molecular epidemiology study; NUCLEOTIDE EXCISION-REPAIR; COMET ASSAY; INTERINDIVIDUAL VARIATION; MUTAGEN SENSITIVITY; PLASMA CAROTENOIDS; CANCER; POLYMORPHISMS; BLOOD; BASE; PROTEIN;
D O I
10.1016/j.dnarep.2014.01.016
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
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 beta-cryptoxanthin and beta-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 at-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. (C) 2014 Elsevier B.V. All rights reserved.
引用
收藏
页码:66 / 73
页数:8
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