Enhancement of the genotoxicity of benzo[a]pyrene by arecoline through suppression of DNA repair in HEp-2 cells
Enhancement of the genotoxicity of benzo[a]pyrene by arecoline through suppression of DNA repair in HEp-2 cells
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DOI：
10.1016/j.tiv.2016.02.007
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发表时间：
2016-06-01
影响因子：
3.2
通讯作者：
Lin, C. S.
中科院分区：
文献类型：
--
作者：
Huang, J. L.;Lu, H. H.;Lin, C. S.
国际癌症研究机构将槟榔果（BQ）和香烟烟雾中的苯并[a]芘（BaP）的主要成分列为1类致癌物。流行病学研究表明，BQ和香烟烟雾的共同暴露会显著增加患癌症的风险。我们之前已经证明槟榔碱，槟榔果中最丰富的生物碱，通过抑制p53活性来抑制核苷酸切除修复。为了研究槟榔碱和BaP在致癌作用中的联合效力，我们用亚细胞毒性剂量的槟榔碱和BaP单独或联合治疗人上皮HEp-2细胞，并检测对DNA损伤和修复的影响。暴露24小时后，BaP增强了DNA修复和p53的活化活性。然而，通过槟榔碱同时处理细胞，这些增强功能被抑制。使用Comet试验，我们发现长时间暴露于槟榔碱和BaP会导致60%的细胞出现中度至重度DNA损伤。BaP治疗1周后，XPD解旋酶的表达受到转录抑制。我们的研究揭示了DNA修复途径中受BQ和烟草成分影响的潜在靶点，以及这些成分对致癌的影响。(C) 2016 Elsevier Ltd.版权所有。
The International Agency for Research on Cancer lists the principal component of betel quid (BQ), the areca nut, and that of cigarette smoke, benzo[a]pyrene (BaP), as Group 1 carcinogens. Epidemiological studies have shown that coexposure of BQ and cigarette smoke markedly increases the risk of cancer. We previously demonstrated that arecoline, the most abundant alkaloid in the areca nut, inhibits nucleotide excision repair through the repression of p53 activity. To investigate the combined potency of arecoline and BaP in carcinogenesis, we treated human epithelial HEp-2 cells with subcytotoxic doses of arecoline and BaP, alone or in combination, and examined the effects on DNA damage and repair. When exposed for 24 h, BaP enhanced DNA repair and p53 transactivation activity. However, these enhancements were suppressed through concurrent treatment of the cells with arecoline. Using a Comet assay, we found that extended exposure to arecoline and BaP caused moderate-to-severe DNA damage in 60% of the cells. Expression of the XPD helicase was transcriptionally suppressed by 1 week of treatment with BaP. Our studies have revealed potential targets in the DNA repair pathway that are affected by BQ and tobacco components, as well as the effect of these components on carcinogenesis. (C) 2016 Elsevier Ltd. All rights reserved.