Resveratrol inhibits benzo[a]pyrene-DNA adduct formation in human bronchial epithelial cells.
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 (32)P-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.
Berge
G
G
Department of Toxicology, National Institute of Occupational Health, PO Box 8149 Dep, Oslo N-0033, Norway.
Øvrebø
S
S
Botnen
I V
IV
Hewer
A
A
Phillips
D H
DH
Haugen
A
A
Mollerup
S
S
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000378:metabolism; D001564:Benzo(a)pyrene; D001980:Bronchi / Q000378:metabolism*; D002478:Cells, Cultured; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism; D065633:Cytochrome P-450 CYP1B1; D018736:DNA Adducts / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000201:enzymology*; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000077185:Resveratrol; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013267:Stilbenes / Q000494:pharmacology*
D000972:Antineoplastic Agents, Phytogenic; D018736:DNA Adducts; D012333:RNA, Messenger; D013267:Stilbenes; C056612:benzo(a)pyrene-DNA adduct; D001564:Benzo(a)pyrene; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1; D000077185:Resveratrol