Coffee diterpenes prevent benzo[a]pyrene genotoxicity in rat and human culture systems.
The coffee-specific diterpenes cafestol and kahweol (C+K) have been identified as two important chemoprotective agents in coffee. In the present study, the potential preventive effects of C+K against the genotoxicity of B[a]P were investigated in rat primary hepatocytes and in human bronchial Beas-2B cells. Several independent mechanisms were identified and their respective contribution to the overall protective effects was determined. A marked dose-dependent inhibition by C+K of B[a]P DNA-binding was found in cells of both origins. However, data showed that the significant induction by C+K of the detoxifying enzyme GST-Yp subunit is the key mechanism of protection against B[a]P DNA-binding in rat liver. In contrast, the phase I-mediated mechanism where C+K produce an inhibition of CYP 1A1 induction by B[a]P is of key significance for the C+K protection in human Beas-2B cells. Moreover, this effect suggests a novel mechanism of chemoprotection by the coffee diterpenes cafestol and kahweol.
Cavin
C
C
Food Safety Group, Nestlé Research Center, P.O. Box 44, Vers-chez-les-Blanc, CH-1000 26, Lausanne, Switzerland. Christophe.Cavin@rdls.nestle.com
Bezencon
C
C
Guignard
G
G
Schilter
B
B
D000818:Animals; D001564:Benzo(a)pyrene; D015153:Blotting, Western; D002470:Cell Survival; D002478:Cells, Cultured; D003069:Coffee; D019363:Cytochrome P-450 CYP1A1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004224:Diterpenes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004976:Ethacrynic Acid / Q000494:pharmacology; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014407:Tumor Cells, Cultured
D003069:Coffee; D004224:Diterpenes; D004791:Enzyme Inhibitors; D001564:Benzo(a)pyrene; C053401:kahweol; D004247:DNA; C053400:cafestol; D019363:Cytochrome P-450 CYP1A1; D005982:Glutathione Transferase; D004976:Ethacrynic Acid