The red wine polyphenol resveratrol reduces polycyclic aromatic hydrocarbon-induced DNA damage in MCF-10A cells.
Polycyclic aromatic hydrocarbons (PAH) are procarcinogens that can be commonly found in our food and environment. Upon biotransformation in our body system, they can cause DNA damage through the generation of genotoxic species and oxidative stress. Phase I and II enzymes are pivotal in the process of proximate carcinogen formation and elimination. Some dietary phytochemicals are strong inhibitors to the phase I enzymes. In the present study, we investigated the effect of the red wine compound resveratrol on DNA damage induced by PAH in a non-tumorigenic breast cell line MCF-10A. Resveratrol ranging from 1 to 5 microm could significantly suppress the expressions of cytochrome P450 (CYP) 1A1, CYP1B1 and UDP-glucuronosyltransferase (UGT) 1A1 induced by 7,12-dimethylbenz[a]anthracene (DMBA). The comet assay indicated that DMBA introduced DNA damage to these cells, and co-treatment of resveratrol at 5 or 10 microm could alleviate the damage. Further investigation illustrated that resveratrol reduced the binding of DMBA metabolites to DNA with no effect on DMBA-induced oxidative DNA damage. Since the phase II enzyme UGT1A1 was suppressed, the elimination of DMBA metabolites would not have contributed to the reduction in the DMBA metabolite-DNA binding. In summary, resveratrol might protect breast cells against PAH-induced DNA damage. The underlying mechanism was mediated by phase I enzyme suppression rather than phase II enzyme induction or oxidative DNA repair.
Leung
Hau Y
HY
Food and Nutritional Sciences Programme, The Chinese University of Hong Kong, Shatin, NT, Hong Kong.
Yung
Lai Hang
LH
Shi
Guoli
G
Lu
A-Lien
AL
Leung
Lai K
LK
D016588:Anticarcinogenic Agents / Q000494:pharmacology; D001551:Benz(a)Anthracenes / Q000633:toxicity*; D045744:Cell Line, Tumor; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects*; D004260:DNA Repair / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D010084:Oxidation-Reduction; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D014920:Wine / Q000032:analysis*
D016588:Anticarcinogenic Agents; D001551:Benz(a)Anthracenes; D013267:Stilbenes; C046810:7,12-dihydroxymethylbenz(a)anthracene; D003577:Cytochrome P-450 Enzyme System; D000077185:Resveratrol