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

Resveratrol inhibits benzo[a]pyrene-DNA adduct formation in human bronchial epithelial cells.
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白藜芦醇抑制人支气管上皮细胞中的苯并[A] pyrene-DNA加合物的形成。

DOI:
10.1038/sj.bjc.6601898
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发表时间:
2004-07-19
影响因子:
8.8
通讯作者:
Mollerup, S
Mollerup, S
中科院分区:
医学1区
文献类型:
--
作者:
Berge, G;Ovrebo, S;Botnen, IV;Hewer, A;Phillips, DH;Haugen, A;Mollerup, S

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白藜芦醇(反式-3,4 ′,5-三羟基芪)是一种存在于多种植物和食物中的植物抗毒素,在一些体外和体内研究中显示出癌症化学预防和化疗潜力。我们研究了白藜芦醇对苯并[a]芘(B[a]P)诱导的人支气管上皮细胞DNA加合物的影响。将其与白藜芦醇对细胞色素P450(CYP)基因CYP 1A 1和CYP 1B 1的表达以及B[a]P代谢产物形成的影响进行比较。BEAS-2 B和BEP 2D细胞暴露于B[a]P和增加浓度的白藜芦醇导致DNA加合物形成的剂量和时间依赖性抑制,通过32 P-后标记定量。支持这一结果,白藜芦醇显示抑制CYP 1A 1和CYP 1B 1基因表达,通过实时逆转录酶-聚合酶链反应测定。此外,DNA加合物的数量和这些基因的mRNA水平之间存在显着的相关性。使用HPLC分析,检测到B[a] P衍生代谢产物的形成同时减少。总之,这些数据支持白藜芦醇在多环芳烃诱导的致癌作用中的化学预防作用。
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 32P-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.
DOI: 10.1093/carcin/23.8.1327
发表时间: 2002-08-01
期刊: CARCINOGENESIS
影响因子: 4.7
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DOI: 10.1016/s0014-5793(97)01572-x
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期刊: FEBS LETTERS
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影响因子: 64.8
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发表时间: 1999-01-27
影响因子: 3.1
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DOI: 10.1016/s0006-2952(01)00763-8
发表时间: 2001-10-15
影响因子: 5.8
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