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

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-ITMS(n) 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 (32)P-postlabeling. We first synthesized and confirmed safrole-dGMP by LC/MS. Two isomeric safrole-dGMPs were characterized as N(2)-(trans-isosafrol-3'-yl) deoxyguanosine and N(2)-(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 (32)P-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 N(2)-(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.

• Authors: Yu-Ting Chung, Chiu-Lan Chen, Cheng-Chung Wu, Shan-An Chan, Chin-Wen Chi, Tsung-Yun Liu
• Journal: Toxicology letters (Toxicol Lett) Vol. 183 Issue 1-3 Pg. 21-7 (Dec 15 2008) ISSN: 0378-4274 [Print] Netherlands
• PMID: 18938230 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA Adducts
• Phosphorus Radioisotopes
• Safrole

Topics

• Alcohol Drinking
• Animals
• Areca (chemistry)
• Carcinoma, Hepatocellular (chemically induced, metabolism)
• Chromatography, Liquid (methods)
• DNA Adducts (analysis, chemistry)
• Female
• Humans
• Injections, Intraperitoneal
• Liver Neoplasms, Experimental (chemically induced, metabolism)
• Male
• Mass Spectrometry (methods)
• Mastication
• Mice
• Mice, Inbred BALB C
• Molecular Structure
• Phosphorus Radioisotopes
• Safrole (administration & dosage, analysis, chemistry)
• Smoking
• Spectrometry, Mass, Electrospray Ionization (methods)
• Taiwan
• Time Factors