Safrole-like DNA adducts in oral tissue from oral cancer patients with a betel quid chewing history
Safrole-like DNA adducts in oral tissue from oral cancer patients with a betel quid chewing history
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DOI：
10.1093/carcin/20.12.2331
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发表时间：
1999-12-01
期刊：
影响因子：
4.7
通讯作者：
Liu, TY
中科院分区：
文献类型：
--
作者：
Chen, CL;Chi, CW;Liu, TY
咀嚼槟榔（BQ）与口腔鳞状细胞癌（OSCC）和口腔粘膜下纤维化（OSF）的风险增加有关。荠菜花序含有 15 mg/g 黄樟素，是台湾独特的 BQ 成分，咀嚼这种制备的 BQ 可能有助于人体暴露黄樟素（唾液中含有 420 μM 黄樟素）。黄樟素是一种已知的啮齿动物肝癌物质，但其对人类的致癌性很大程度上尚未确定。在本研究中，使用 P-32 后标记方法，我们发现 BQ 相关 OSCC (77%, 23/30) 和非癌性匹配组织 (NCMT) (97%, 29/30) 中黄樟素样 DNA 加合物的频率较高，这与所有非 BQ 相关 OSCC 及其配对中此类加合物的缺失（< 1/10(9) 核苷酸）形成鲜明对比。 NCMT（P < 0.001）。 7 个 OSF 中的 6 个也表现出相同的黄樟素样 DNA 加合物，OSF 和 NCMT 中的 DNA 加合物水平显着高于 OSCC（P < 0.05）。使用共色谱和重色谱技术，我们进一步证明这些加合物与合成黄樟素-dGMP 加合物以及来自 1'-羟基黄樟素处理的 HepG2 细胞的 DNA 加合物相同。这些结果表明，咀嚼BQ后，黄樟素在人体口腔组织中形成稳定的黄樟素-DNA加合物，这可能有助于口腔癌的发生。
Betel quid (BQ) chewing has been associated with an increased risk of oral squamous cell carcinoma (OSCC) and oral submucous fibrosis (OSF). Piper betle inflorescence, which contains 15 mg/g safrole, is a unique ingredient of BQ in Taiwan, Chewing such prepared BQ may contribute to safrole exposure in human beings (420 mu M safrole in saliva). Safrole is a known rodent hepatocarcinogen, yet its carcinogenicity in human beings is largely undetermined. In this study, using a P-32-post-labeling method, we have found a high frequency of safrole-like DNA adducts in BQ-associated OSCC (77%, 23/30) and non-cancerous matched tissue (NCMT) (97%, 29/30), This was in contrast to the absence (< 1/10(9) nucleotides) of such adducts in all of non-BQ-associated OSCC and their paired NCMT (P < 0.001). Six of seven OSF also exhibited the same safrole-like DNA adduct, The DNA adduct levels in OSF and NCMT were significantly higher than in OSCC (P < 0.05). Using co-chromatography and rechromatography techniques, we further demonstrated that these adducts were identical to synthetic safrole-dGMP adducts as well as DNA adducts from 1'-hydroxysafrole-treated HepG2 cells. These results suggest that safrole forms stable safrole-DNA adducts in human oral tissue following BQ chewing, which may contribute to oral carcinogenesis.