title: Protection by quercetin and quercetin-rich fruit juice against induction of oxidative DNA damage and formation of BPDE-DNA adducts in human lymphocytes.
abstract: Flavonoids are claimed to protect against cardiovascular disease, certain forms of cancer and ageing, possibly by preventing initial DNA damage. Therefore, we investigated the protective effects of the flavonoid quercetin against the formation of oxidative DNA damage and bulky DNA adducts in human lymphocytes, both in vitro and ex vivo. First, human lymphocytes were pre-incubated with various concentrations of quercetin, followed by incubation with hydrogen peroxide; protection against oxidative DNA damage was evaluated by use of the single-cell gel electrophoresis (Comet) assay. Second, quercetin-treated human lymphocytes were challenged by treatment with benzo(a)pyrene (B(a)P), and BPDE-DNA adduct formation was measured by (32)P-postlabelling. Third, in a pilot study, lymphocytes from female volunteers who consumed a quercetin-rich blueberry/apple juice mixture for four weeks, were treated ex vivo with an effective dose of H(2)O(2) and benzo(a)pyrene, respectively, at three different time points, i.e. before (t=0 weeks), during (t=2 weeks) and after (t=4 weeks) the intervention. Results in vitro: a significant dose-dependent protection by quercetin against both the formation of oxidative DNA damage (p<0.01) and of BPDE-DNA adducts (p<0.05) was observed. Results in vivo: four weeks of juice intervention led to a significant increase in the total antioxidant capacity of plasma, as reflected by the increase of the TEAC value from 773 microM trolox equivalent at t=0 to 855 microM at t=4 weeks (p=0.04) and an increase in plasma quercetin content from 5.0 to 10.6 nM (p=0.03). After intervention, the level of oxidative damage upon ex vivo exposure to H(2)O(2) was non-significantly (p=0.07) decreased by 41%, and the BPDE-DNA adduct level induced ex vivo was non-significantly decreased by 11%. The combination of our findings in vitro and ex vivo provides evidence that quercetin is able to protect against chemically induced DNA damage in human lymphocytes, which may underlie its suggested anticarcinogenic properties.
authors.affiliation: Department of Health Risk Analysis and Toxicology, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands. L.Wilms@GRAT.unimaas.nl
authors.forename: Lonneke C
authors.initials: LC
authors.lastname: Wilms
authors.forename: Peter C H
authors.initials: PC
authors.lastname: Hollman
authors.forename: Agnes W
authors.initials: AW
authors.lastname: Boots
authors.forename: Jos C S
authors.initials: JC
authors.lastname: Kleinjans
mesh_terms: D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D000328:Adult; D001628:Beverages; D020552:Comet Assay; D018736:DNA Adducts / Q000096:biosynthesis*; D004249:DNA Damage; D005260:Female; D005638:Fruit; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D018384:Oxidative Stress; D011794:Quercetin / Q000097:blood / Q000494:pharmacology*
chemical_list: D018736:DNA Adducts; C043931:benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide-DNA; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D011794:Quercetin