Effects of micronutrients on DNA repair
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DNA repair is an essential cellular function, which, by removing DNA damage before it can cause mutations, contributes crucially to the prevention of cancer. Interest in the influence of micronutrients on DNA repair activity is prompted by the possibility that the protective effects of fruits and vegetables might thus be explained. Two approaches to measuring repair—monitoring cellular removal of DNA damage and incubating cell extract with specifically damaged DNA in an in vitro assay—have been applied in cell culture, whole animal studies, and human trials. In addition, there are numerous investigations at the level of expression of DNA repair–related genes.
Depending on the pathway studied and the phytochemical or food tested, there are varied reports of stimulation, inhibition or no effect on DNA repair. The clearest findings are from human supplementation trials in which lymphocytes are assessed for their repair capacity ex vivo. Studying cellular repair of strand breaks is complicated by the fact that lymphocytes appear to repair them very slowly. Applying the in vitro repair assay to human lymphocytes has revealed stimulatory effects on repair of oxidised bases by various micronutrients or a fruit- and vegetable-rich diet, while other studies have failed to demonstrate effects.
Despite varied results from different studies, it seems clear that micronutrients can influence DNA repair, usually but not always enhancing activity. Different modes of DNA repair are likely to be subject to different regulatory mechanisms. Measures of gene expression tend to be a poor guide to repair activity, and there is no substitute for phenotypic assays.
KeywordsDNA repair Base excision repair Nucleotide excision repair Micronutrients Antioxidants
AA thanks the Ministerio de Educación y Ciencia (‘Juan de la Cierva’ programme, 2009) of the Spanish Government for its contribution to the financial support for this work. The Centre for Brain Ageing & Vitality is funded through the Lifelong Health and Wellbeing cross-council initiative by the MRC, BBSRC, EPSRC and ESRC.
Conflict of interest
The authors declare that they have no conflict of interest in preparing this review article.
- 1.WCRF/AICR (2007) Food, nutrition, physical activity, and the prevention of cancer. American Institute for Cancer Research, Washington, pp 1–517Google Scholar
- 4.ESCODD, Gedik CM, Collins A (2005) Establishing the background level of base oxidation in human lymphocyte DNA: results of an interlaboratory validation study. FASEB J 19:82–84Google Scholar
- 6.Miller ER III, Pastor-Barriuso R, Dalal D, Riemersma RA, Appel LJ, Guallar E (2005) Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med 142:37–46Google Scholar
- 9.Collins AR, Azqueta A (2012) DNA repair as a biomarker in human biomonitoring studies; further applications of the comet assay. Mutat Res. doi: 10.1016/j.mrfmmm.2011.03.005
- 24.Duthie SJ, Collins AR, Duthie GG, Dobson VL (1997) Quercetin and myricetin protect against hydrogen peroxide-induced DNA damage (strand breaks and oxidised pyrimidines) in human lymphocytes. Mutat Res 393:223–231Google Scholar
- 32.Bouhlel I, Valenti K, Kilani S, Skandrani I, Ben Sghaier M, Mariotte AM, Dijoux-Franca MG, Ghedira K, Hininger-Favier I, Laporte F, Chekir-Ghedira L (2008) Antimutagenic, antigenotoxic and antioxidant activities of Acacia salicina extracts (ASE) and modulation of cell gene expression by H2O2 and ASE treatment. Toxicol In Vitro 22:1264–1272CrossRefGoogle Scholar
- 36.Henning SM, Mckee RW, Swendseid ME (1989) Hepatic poly(ADP ribose) polymerase activity in methyl donor-deficient rats. J Nutr 119:1528–1531Google Scholar
- 39.Pogribny IP, Basnakian AG, Miller BJ, Lopatina NG, Poirier LA, James SJ (1995) Breaks in genomic DNA and within the p53 gene are associated with hypomethylation in livers of folate/methyl-deficient rats. Cancer Res 55:1894–1901 (Erratum in: Cancer Res 1995, 55:2711)Google Scholar
- 40.Zhang JZ, Henning SM, Swendseid ME (1993) Poly(ADP-Ribose) polymerase activity and DNA strand breaks are affected in tissues of niacin-deficient rats. J Nutr 123:1349–1355Google Scholar
- 41.Rawling JM, Jackson TM, Driscoll ER, Kirkland JB (1994) Dietary niacin deficiency lowers tissue poly(ADP-ribose) and NAD+ concentrations in Fischer-344 rats. J Nutr 124:1597–1603Google Scholar
- 42.Henning SM, Swendseid ME, Coulson WF (1997) Male rats fed methyl- and folate-deficient diets with or without niacin develop hepatic carcinomas associated with decreased tissue NAD concentrations and altered poly(ADP-ribose) polymerase activity. J Nutr 127:30–36Google Scholar
- 45.Webster RP, Gawde MD, Bhattacharya RK (1996) Effect of different vitamin A status on carcinogen-induced DNA damage and repair enzymes in rats. In Vivo 10:113–118Google Scholar
- 46.Webster RP, Gawde MD, Bhattacharya RK (1996) Modulation by dietary copper of aflatoxin B1-induced activity of DNA repair enzymes poly (ADP-ribose) polymerase, DNA polymerase beta and DNA ligase. In Vivo 10:533–536Google Scholar
- 52.Langie SA, Kowalczyk P, Tudek B, Zabielski R, Dziaman T, Olinski R, van Schooten FJ, Godschalk RW (2010) The effect of oxidative stress on nucleotide-excision repair in colon tissue of newborn piglets. Mutat Res 1–2:75–80Google Scholar
- 53.Langie SAS, Kowalczyk P, Tomaszewski B, Maas LM, Moonen EJ, Godschalk RWL, Tudek B, van Schooten FJ, Zabielski R, Mathers JC (2012) Redox regulation and epigenetic regulation of the APE1 gene in the brain of young piglets: the effect of early life exposures. Abstracts from the 9th International Comet Assay Workshop held in Kusadasi, Turkey; 13–16 Sep 2011. Mutagenesis (in press)Google Scholar
- 55.Collins AR, Ma A, Duthie SJ (1995) The kinetics of repair of oxidative DNA damage (strand breaks and oxidised pyrimidines) in human cells. Mutat Res 336:69–77Google Scholar
- 56.Collins AR, Duthie SJ, Fillion L, Gedik CM, Vaughan N, Wood SG (1997) Oxidative DNA damage in human cells: the influence of antioxidants and DNA repair. Biochem Soc Trans 25:326–331Google Scholar
- 59.Tomasetti M, Alleva R, Borghi B, Collins AR (2001) In vivo supplementation with coenzyme Q10 enhances the recovery of human lymphocytes from oxidative DNA damage. FASEB J 15:1425–1427Google Scholar
- 68.Bøhn SK, Myhrstad MC, Thoresen M, Holden M, Karlsen A, Tunheim SH, Erlund I, Svendsen M, Seljeflot I, Moskaug JØ, Duttaroy AK, Laake P, Arnesen H, Tonstad S, Collins A, Drevon CA, Blomhoff R (2010) Blood cell gene expression associated with cellular stress defense is modulated by antioxidant-rich food in a randomised controlled clinical trial of male smokers. BMC Med. http://www.biomedcentral.com/1741-7015/8/54
- 69.Møller P, Vogel U, Pedersen A, Dragsted LO, Sandström B, Loft S (2003) No effect of 600 grams fruit and vegetables per day on oxidative DNA damage and repair in healthy nonsmokers. Cancer Epi Biomark Prev 12:1016–1022Google Scholar
- 71.Mathers JC, Strathdee G, Relton CL (2010) Induction of epigenetic alterations by dietary and other environmental factors. In: Herceg Z, Ushijima T (eds) Advances in genetics, vol 71. Academic Press, Burlington, pp 1–39Google Scholar
- 75.Fang MZ, Wang Y, Ai N, Hou Z, Sun Y, Lu H, Welsh W, Yang CS (2003) Tea polyphenol (2)-epigallocatechin-3-gallate inhibits DNA methyltransferase and reactivates methylation-silenced genes in cancer cell lines. Cancer Res 63:7563–7570Google Scholar
- 77.Langie SA, Tomaszewski B, Cameron KM, Fletcher KP, Lisanti S, Godschalk RW, van Schooten FJ, von Zglinicki T, Mathers JC (2011) The ageing brain: effects on DNA repair and DNA methylation in mice. In: Abstracts of UKEMS/Dutch EMS-sponsored workshop on biomarkers of exposure and oxidative DNA damage and 7th GUM 32P-Postlabelling Workshop, Münster, Germany; March 28–29, 2011. Mutagenesis 26:706Google Scholar
- 79.Dusinska M, Lietava J, Olmedilla B, Raslova K, Southon S, Collins AR (1999) Indicators of oxidative stress, antioxidants and human health. In: Basu TK, Temple NJ, Garg ML (eds) Antioxidants in human health. CAB International, Wallingford, pp 411–422Google Scholar
- 80.Obtulowicz T, Swoboda M, Speina E, Gackowski D, Rozalski R, Siomek A, Janik J, Janowska B, Ciesla JM, Jawien A, Banaszkiewicz Z, Guz J, Dziaman T, Szpila A, Olinski R, Tudek B (2010) Oxidative stress and 8-oxoguanine repair are enhanced in colon adenoma and carcinoma patients. Mutagenesis 25:463–471CrossRefGoogle Scholar