title: The effect of plant phenolics on the formation of 7,12-dimethylbenz[a]anthracene-DNA adducts and TPA-stimulated polymorphonuclear neutrophils chemiluminescence in vitro.
abstract: Phenolics, common plant constituents, form up an important part of human diet and are considered potential chemopreventive agents. In the present study, structurally diverse phenolics, such as tannic acid, protocatechuic acid, chlorogenic acid and resveratrol, were investigated for their inhibitory effects on covalent binding of 7,12-dimethylbenz[a]anthracene (DMBA) to DNA in vitro and the suppression of oxidative burst in 12-O-tetradecanoylphorbol-13-acetate (TPA)-stimulated human polymorphonuclear neutrophils (PMNs). 32P-postlabeling analysis of DNA incubated with DMBA in the presence of 3-methylcholanthrene (3-MC)-induced microsomes produced three major adducts derived from anti-, syn- and anti-dihydrodiol epoxides through reactions with dGuo and dAdo, respectively. Phenolic compounds at the concentration of 150 microM reduced the levels of all DMBA-DNA adducts by 55-98%. The most dramatic effect was observed in case of tannic acid, which completely inhibited the formation of DMBA-dAdo adducts. Chlorogenic acid was the least effective inhibitor of DMBA-DNA adducts formation particularly syn-DMBADE-dAdo (20%). Human neutrophils showed a significant dose-related decrease of TPA-induced chemiluminescence after pretreatment with phenolic compounds. The most effective inhibitors were tannic acid and resveratrol with IC(50)=5.19 and 5.76 microM, respectively. These results suggest that the suppression of reactive oxygen species (ROS) and carcinogen-DNA adducts formation may be important for anticarcinogenic activity of the examined phenolics.
authors.affiliation: Department of Pharmaceutical Biochemistry, Karol Marcinkowski University of Medical Sciences, Grunwaldzka 6, Poznan 60-780, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Ignatowicz
authors.forename: Bartosz
authors.initials: B
authors.lastname: Balana
authors.forename: Suryanarayana V
authors.initials: SV
authors.lastname: Vulimiri
authors.forename: Hanna
authors.initials: H
authors.lastname: Szaefer
authors.forename: Wanda
authors.initials: W
authors.lastname: Baer-Dubowska
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene / Q000031:analogs & derivatives* / Q000378:metabolism*; D000818:Animals; D002726:Chlorogenic Acid / Q000494:pharmacology; D004247:DNA / Q000378:metabolism*; D018736:DNA Adducts / Q000096:biosynthesis*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D047348:Hydrolyzable Tannins / Q000494:pharmacology; D062385:Hydroxybenzoates / Q000494:pharmacology; D008163:Luminescent Measurements; D008297:Male; D008748:Methylcholanthrene / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D010636:Phenols / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D016897:Respiratory Burst / Q000187:drug effects; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
chemical_list: C059444:7,12-dimethylbenz(a)anthracene-DNA adduct; D018736:DNA Adducts; D004791:Enzyme Inhibitors; D047348:Hydrolyzable Tannins; D062385:Hydroxybenzoates; D010636:Phenols; D017382:Reactive Oxygen Species; D013267:Stilbenes; D002726:Chlorogenic Acid; C009091:protocatechuic acid; D008748:Methylcholanthrene; D015127:9,10-Dimethyl-1,2-benzanthracene; D004247:DNA; D013755:Tetradecanoylphorbol Acetate; D000077185:Resveratrol