槟榔致癌物质与口腔癌.pdf

国际口胚医学杂志第41卷1期2014年1
www.g]kqyxzz.cn
槟榔致癌物质与口腔癌
黄龙翦新春
中南大学湘雅医院口腔颌面外科长沙410008
[摘要」槟榔为一级致癌物,咀嚼槟榔引起口腔癌缘于槟榔中的槟榔帔(ARC)、槟榔鞣质、槟榔特异性亚硝胺
(ASNA)和活性氧(ROS)等具有细胞毒性、遗传毒性、致突変性和致癌性。ARC可诱导口腔成纤维细胞、角
质形成细胞和人脐静脉内皮细胞程序性死亡。槟榔鞣质冇否遗传毒性和致突变性至今仍有争议,不同类型的短期
筛选试验结果差异很大,但含輮质的槟榔多酚是槟椰的主要致癌成分。3-甲基亚硝氨基内醛可诱发人黏膜角
质形成细胞的DNA链断裂和DNA蛋白交联。3-甲基亚硝氨基丙腈为强致癌剂,可诱发试验动物肿瘤,靶器官包括
鼻腔、食管、舌等。槟榔咀嚼过程中可产生大量的ROS,造成DNA氧化性损伤和激活癌基因的方式促使癌症的发
生。相对分子质量为3.0×104-10.0×1°的槟挪提取物组分中一种新发现的蛋白聚糖通过增加胞内ROS水平及一系
列信号级联放大,上调口腔癌细胞低氧诱导因子-1的表达,最终诱导细胞自曚。细胞自噬有利于保护癌细胞免
遭ARC诱导的程序性细胞死亡,促进口腔癌的发展。槟榔提取物述可能通过ROS增强舌鱗状上皮细胞癌细胞株刺
激血小板聚集的效应,从而促进舌癌转移。
[关键词]」槟榔;∏腔癌;椗榔碱;輮质;槟榔特异性亚硝胺;活性氧
中图分类号]Q51[文献标志码] A doil10.7518/gkq-2014.01.023
Areca nut-related carcinogens and oral cancer Huang Long, ian inchun. (Dept. of Oral and Maxillofacial Surgery.
Xiangya Hospital, Central South University, Changsha 410008, China)
Iabstract] Areca nut is a recently confirmed class I careinogen. The areca nut chewing habit is a primary environmental
risk factor for the development of oral cancer due to cytotoxicity, genotoxicity, mutagenicity, and carcinogenicity
of arecoline(ARC), areca-containing tannins areca-specific nitrosamine(ASNA), and reactive oxygen species(ROS
produced during areca nut chewing. ARC is capable of inducing apoptosis of oral fibroblasts, keratinocytes, and human
umbilical vein endothelial cells. The results of different types of short-term sereening tests differ, so the genotoxicity
mutagenicity of areca-containing tannins remain controversial. Tannin-ontaining polyphenolic fraction is a primary
carcinogenic ingredient. 3-methyl-nitrosamino propionaldehyde can induce DNA strand breakage and Dna-protein cross
linkage for human buccal keratinocytes. 3-methyl-nitrosamino propionitrile is a potent carcinogen that can induce nasal
esophageal, and tongue tumors in laboratory animals. ROS produced during areca nut chewing can promote tumorigenesis
by inducing DNA oxidative damage and activating oncogenes. A newly found proteoglycan in the 3.010#to 100x
relative molecular mass fraction of areca nut extract induces oxidative stress and modulates a signaling cascade that
upregulates hypoxia, inducing factor-la expression in oral cancer cells, which eventually leads to autophagy. Autophagy
can help cancer cells survive Arc-induced apoptosis and promote the development of oral cancer. Areca nut extract can
enhance tongue cancer cell-induced platelet aggregation by generating ROS, thus promoting tongue cancer metastasis
Key words areca nut; oral cancer; arecoline; tannin; areca-specific nitrosamine; reactive oxygen species
咀嚼槟榔是主要流行于南亚地区、南太平洋地区和南非地区以及中国的台湾地区和湖南省的
[收稿日期]2013-06-23;[修回日期]2013-10-11
种传统习俗。咀嚼槟榔可引起口腔黏膜下纤维
基金项目了卫生部临床重点专科建设项目(2071)
化( oral submucous fibrosis,OSF),OSF是一种
作者简介黄龙,主治医师,博士,Email:huanglong0129126.com
癌前病变,经过长期的慢性病理过程可恶变为口
通讯作者]翦新春,教授、硕士, Email: jianxinchun(@houma].om
腔瘋刂。咀嚼槟榔之所以能导致口腔癌,是因为槟