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

doi:10.1016/j.toxlet.2008.09.013

Chia Nan University of Pharmacy & Science Institutional Repository > 藥理學院 > 藥學系(所) > 期刊論文 > Item 310902800/21738

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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
顯示於類別:	[藥學系(所)] 期刊論文

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