Cavin C, Bezencon C, Guignard G, Schilter B
Food Safety Group, Nestlé Research Center, P.O. Box 44, Vers-chez-les-Blanc, CH-1000 26, Lausanne, Switzerland.
Biochem Biophys Res Commun. 2003 Jun 27;306(2):488-95. doi: 10.1016/s0006-291x(03)00994-x.
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.
咖啡特有的二萜类化合物咖啡醇和咖啡豆醇（C+K）已被确定为咖啡中的两种重要化学保护剂。在本研究中，在大鼠原代肝细胞和人支气管Beas-2B细胞中研究了C+K对苯并[a]芘遗传毒性的潜在预防作用。确定了几种独立机制，并确定了它们对总体保护作用的各自贡献。在两种来源的细胞中均发现C+K对苯并[a]芘DNA结合有明显的剂量依赖性抑制作用。然而，数据表明，C+K对解毒酶GST-Yp亚基的显著诱导是大鼠肝脏中防止苯并[a]芘DNA结合的关键保护机制。相反，C+K通过I相介导机制抑制苯并[a]芘诱导的CYP 1A1，这对人Beas-2B细胞中的C+K保护具有关键意义。此外，这种作用提示了咖啡二萜类化合物咖啡醇和咖啡豆醇的一种新的化学保护机制。
