Resveratrol inhibits benzo[a]pyrene-DNA adduct formation in human bronchial epithelial cells

被引:31
作者
Berge, G
Ovrebo, S
Botnen, IV
Hewer, A
Phillips, DH
Haugen, A
Mollerup, S
机构
[1] Norwegian Inst Occupat Hlth, Dept Toxicol, N-0033 Oslo, Norway
[2] Inst Canc Res, Sect Mol Carcinogenesis, Sutton SM2 5NG, Surrey, England
关键词
DNA adducts; cytochrome P450; human bronchial epithelial cells; metabolites; PAH; real-time RT-PCR; resveratrol;
D O I
10.1038/sj.bjc.6601898
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Resveratrol ( trans-3,4',5-trihydroxystilbene), a phytoalexin present in various plants and foods, has in several in vitro and in vivo studies demonstrated cancer chemopreventive and chemotherapeutic potential. We investigated the in vitro effect of resveratrol on benzo[ a] pyrene ( B[ a] P)-induced DNA adducts in human bronchial epithelial cells. This was compared to the effect of resveratrol on the expression of the cytochrome P450 (CYP) genes CYP1A1 and CYP1B1 and the formation of B[ a] P metabolites. Exposure of BEAS-2B and BEP2D cells to B[ a] P and increasing concentrations of resveratrol resulted in a dose- and time-dependent inhibition of DNA adduct formation quantified by P-32-postlabelling. Supporting this result, resveratrol was shown to inhibit CYP1A1 and CYP1B1 gene expression, as measured by real-time reverse transcriptase - polymerase chain reaction. Also, a significant correlation was found between the number of DNA adducts and the mRNA levels of these genes. Using HPLC analysis, a concomitant decrease in the formation of B[ a]P-derived metabolic products was detected. In conclusion, these data lend support to a chemopreventive role of resveratrol in polycyclic aromatic hydrocarbon-induced carcinogenesis.
引用
收藏
页码:333 / 338
页数:6
相关论文
共 38 条
[1]  
Ahmad N, 2001, CLIN CANCER RES, V7, P1466
[2]   Epidemiology, etiology, and prevention of lung cancer [J].
Bilello, KS ;
Murin, S ;
Matthay, RA .
CLINICS IN CHEST MEDICINE, 2002, 23 (01) :1-+
[3]   Resveratrol, a natural product present in wine, decreases tumour growth in a rat tumour model [J].
Carbó, N ;
Costelli, P ;
Baccino, FM ;
López-Soriano, FJ ;
Argilés, JM .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1999, 254 (03) :739-743
[4]  
Casper RF, 1999, MOL PHARMACOL, V56, P784
[5]   Trans-resveratrol modulates the catalytic activity and mRNA expression of the procarcinogen-activating human cytochrome P4501B1 [J].
Chang, TKH ;
Lee, WBK ;
Ko, HH .
CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY, 2000, 78 (11) :874-881
[6]   Resveratrol is a selective human cytochrome P450 1A1 inhibitor [J].
Chun, YJ ;
Kim, MY ;
Guengerich, FP .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1999, 262 (01) :20-24
[7]  
Ciolino HP, 1999, MOL PHARMACOL, V56, P760
[8]   Alcohol intake and risk of adenocarcinoma of the lung -: A case-control study in Uruguay [J].
De Stefani, E ;
Correa, P ;
Deneo-Pellegrini, H ;
Boffetta, P ;
Gutiérrez, LP ;
Ronco, A ;
Brennan, P ;
Mendilaharsu, M .
LUNG CANCER, 2002, 38 (01) :9-14
[9]   Preferential formation of benzo[a]pyrene adducts at lung cancer mutational hotspots in P53 [J].
Denissenko, MF ;
Pao, A ;
Tang, MS ;
Pfeifer, GP .
SCIENCE, 1996, 274 (5286) :430-432
[10]   Human extrahepatic cytochromes P450: Function in xenobiotic metabolism and tissue-selective chemical toxicity in the respiratory and gastrointestinal tracts [J].
Ding, XX ;
Kaminsky, LS .
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, 2003, 43 :149-173