Nutritional modulation of DNA repair in a human intervention study.
DNA oxidation is a potential cause of cancer in humans. It is well-known that fruits and vegetables protect against cancer, and this may be in part because they contain antioxidants, which decrease the level of oxidation of DNA. However, there are other possible mechanisms, such as an enhancement of cellular repair of this damage. A randomized cross-over study was carried out on healthy human subjects, who were given kiwifruit as a supplement to their normal diet, for 3-week periods at different 'doses', with 2-week washout periods between doses. Endogenous oxidation of bases in lymphocyte DNA, and the resistance of the DNA to oxidation ex vivo, were assessed using single cell gel electrophoresis (the 'comet assay'). The capacity to repair DNA base oxidation was measured with an in vitro test, and levels of expression of repair-related genes OGG1 and APE1 were assessed by semi-quantitative RT-PCR. Concentrations of dietary antioxidants were measured in plasma. The antioxidant status of plasma and of lymphocytes was increased by consumption of kiwifruit. Levels of endogenous oxidation of pyrimidines and purines in DNA were markedly decreased, and DNA repair measured on a substrate containing 8-oxo-7,8-dihydroguanine was substantially increased (without change in levels of OGG1 or APE1 mRNA). The magnitude of these effects was generally not related to the number of kiwifruits consumed per day. Kiwifruit provides a dual protection against oxidative DNA damage, enhancing antioxidant levels and stimulating DNA repair. It is probable that together these effects would decrease the risk of mutagenic changes leading to cancer.
Collins
Andrew R
AR
Institute for Nutrition Research, University of Oslo, POB 1046 Blindern, N-0316 Oslo, Norway. a.r.collins@basalmed.uio.no
Harrington
Vikki
V
Drew
Janice
J
Melvin
Rachel
R
D000328:Adult; D001483:Base Sequence; D019757:Carbon-Oxygen Lyases / Q000235:genetics; D018592:Cross-Over Studies; D004249:DNA Damage; D017931:DNA Primers; D004260:DNA Repair; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D043382:DNA-Formamidopyrimidine Glycosylase; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009699:N-Glycosyl Hydrolases / Q000235:genetics; D009747:Nutritional Physiological Phenomena; D018384:Oxidative Stress; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers; D009699:N-Glycosyl Hydrolases; D043382:DNA-Formamidopyrimidine Glycosylase; D019757:Carbon-Oxygen Lyases; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase