Safrole-DNA adduct in hepatocellular carcinoma associated with betel quid chewing

doi:10.1016/j.toxlet.2008.09.013

CNU IR > Pharmacy and Science > Dept. of Pharmacy > Periodical Articles > Item 310902800/21738

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

Title:	Safrole-DNA adduct in hepatocellular carcinoma associated with betel quid chewing
Authors:	Yu-Ting Chung Chiu-Lan Chen Cheng-Chung Wu Shan-An Chan Chin-Wen Chi Tsung-Yun Liu
Contributors:	藥學系
Keywords:	HCC LC/ESI-ITMSn LC/QTOF-MS 32P-postlabeling Safrole-DNA adduct
Date:	2008-12
Issue Date:	2009-10-13 10:53:00 (UTC+8)
Abstract:	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.
Relation:	Toxicology Letters 183(1-3)：p.21-27
Appears in Collections:	[Dept. of Pharmacy] Periodical Articles

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