title: Evidence that dietary supplementation with carotenoids and carotenoid-rich foods modulates the DNA damage: repair balance in human lymphocytes.
abstract: Epidemiological evidence has shown that the habitual consumption of diets high in fruits and vegetables is associated with reduced risk of cancers. The challenge is to identify causal mechanisms of effect. The aim of the current study was to determine whether an increase in rate of removal of DNA single-strand breaks (SSB) following oxidative challenge could be provoked ex vivo in peripheral blood lymphocytes (PBL). The PBL were isolated from apparently healthy volunteers following dietary intervention with: (1) a mixed carotene capsule; (2) a daily portion of cooked minced carrots; (3) a matched placebo; (4) a portion of mandarin oranges; (5) vitamin C tablets. Single-cell gel electrophoresis was employed to measure baseline levels of SSB and DNA susceptibility to oxidative damage, and to monitor the number of SSB over 4 h, in both unchallenged and H2O2-treated PBL. The enzymatic capacity for repair of different types of DNA oxidative lesions was also measured using two related cell-free assays. There was no evidence that any of the dietary supplementation regimens altered baseline levels of SSB, provided any direct antioxidant protection or altered DNA repair capacity, with two exceptions: the number of SSB following exposure to H2O2 decreased more rapidly in PBL from volunteers given the mixed carotene capsules and repair patch synthesis activity in PBL increased from volunteers given the cooked carrots. These results suggest that carotenoids and carotenoid-rich foods can influence DNA damage:repair by modulation of discrete stages in the DNA repair mechanisms.
authors.affiliation: Institute of Food Research, Norwich Research Park, Colney, Norwich NR4 7UA, UK. sian.astley@bbsrc.ac.uk
authors.forename: Siân B
authors.initials: SB
authors.lastname: Astley
authors.forename: Ruan M
authors.initials: RM
authors.lastname: Elliott
authors.forename: David B
authors.initials: DB
authors.lastname: Archer
authors.forename: Susan
authors.initials: S
authors.lastname: Southon
mesh_terms: D000293:Adolescent; D000328:Adult; D016588:Anticarcinogenic Agents / Q000097:blood; D000975:Antioxidants / Q000008:administration & dosage* / Q000032:analysis; D002338:Carotenoids / Q000008:administration & dosage* / Q000097:blood; D065366:Cryptoxanthins; D004249:DNA Damage / Q000187:drug effects* / Q000235:genetics; D004260:DNA Repair; D004277:DNA, Single-Stranded / Q000235:genetics; D019587:Dietary Supplements; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction / Q000187:drug effects; D024505:Tocopherols / Q000097:blood; D024341:Xanthophylls; D019207:beta Carotene / Q000031:analogs & derivatives* / Q000097:blood
chemical_list: D016588:Anticarcinogenic Agents; D000975:Antioxidants; D065366:Cryptoxanthins; D004277:DNA, Single-Stranded; D024341:Xanthophylls; D019207:beta Carotene; D002338:Carotenoids; D024505:Tocopherols