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    Please use this identifier to cite or link to this item: http://ir.cnu.edu.tw/handle/310902800/21738


    標題: Safrole-DNA adduct in hepatocellular carcinoma associated with betel quid chewing
    作者: Yu-Ting Chung
    Chiu-Lan Chen
    Cheng-Chung Wu
    Shan-An Chan
    Chin-Wen Chi
    Tsung-Yun Liu
    貢獻者: 藥學系         
    關鍵字: HCC
    LC/ESI-ITMSn
    LC/QTOF-MS
    32P-postlabeling
    Safrole-DNA adduct
    日期: 2008-12
    上傳時間: 2009-10-13 10:53:00 (UTC+8)
    摘要: Betel quid chewing, which contributes high concentration of safrole in saliva, is a popular oral habit in Taiwan. Safrole is a documented rodent hepatocarcinogen, yet its hepatocarcinogenic potential in human is not known. Here, we used LC/ESI-ITMSn and LC/QTOF-MS confirmed safrole-dGMP as reference standard to detect the safrole-DNA adduct in hepatic tissues from HBsAg-/HCV-seronegative hepatocellular carcinoma patients by 32P-postlabeling. We first synthesized and confirmed safrole-dGMP by LC/MS. Two isomeric safrole-dGMPs were characterized as N2-(trans-isosafrol-3′-yl) deoxyguanosine and N2-(safrol-1′-yl) deoxyguanosine. This technique was able to detect hepatic safrole-DNA adduct in mice that were treated with safrole but not sensitive enough to detect safrole-DNA adduct in human samples. Using the nuclease P1 version of the 32P-postlabeling technique, we detected the presence of safrole-DNA adduct in two out of 28 hepatic tissues from hepatocellular carcinoma patients, and only these two patients had a history of betel quid chewing lasting more than 10 years. From co-chromatography with the mass confirmed safrole-dGMPs, this safrole-DNA adduct was identified as N2-(trans-isosafrol-3′-yl) deoxyguanosine. These results suggest that betel quid-containing safrole might be involved in the pathogenesis of hepatocellular carcinoma in human beings and LC/MS has the potential to identify DNA adducts in clinical samples.
    關聯: Toxicology Letters 183(1-3):p.21-27
    Appears in Collections:[藥學系(所)] 期刊論文

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