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.