High Excretion of Etheno Adducts in Liver Fluke–Infected Patients: Protection by Praziquantel against DNA Damage

• Published in: Cancer epidemiology, biomarkers & prevention Vol. 17; no. 7; pp. 1658 - 1664
• Main Authors: Dechakhamphu, Somkid, Yongvanit, Puangrat, Nair, Jagadeesan, Pinlaor, Somchai, Sitthithaworn, Paiboon, Bartsch, Helmut
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.07.2008
• Subjects: Adult; Animals; Anthelmintics - pharmacology; Bile Duct Neoplasms - epidemiology; Bile Duct Neoplasms - etiology; Bile Duct Neoplasms - prevention & control; Bile Ducts, Intrahepatic; Biological and medical sciences; cholangiocarcinoma; Cholangiocarcinoma - epidemiology; Cholangiocarcinoma - etiology; Cholangiocarcinoma - prevention & control; Chromatography, High Pressure Liquid; Deoxyadenosines - urine; Deoxycytidine - analogs & derivatives; Deoxycytidine - urine; DNA Adducts - urine; DNA Damage - drug effects; etheno DNA adducts; Feces - parasitology; Female; Humans; Immunoprecipitation; Incidence; inflammation; lipid peroxidation; Male; Medical sciences; Middle Aged; Opisthorchiasis - complications; Opisthorchiasis - epidemiology; Opisthorchiasis - urine; Opisthorchis - isolation & purification; Opisthorchis viverrini; Oxidative Stress; Praziquantel - pharmacology; Risk Factors; Thailand - epidemiology; Tumors; Thailand; High; Human; Excretion; Isoquinoline derivatives; Anthelmintic; Digestive system; Praziquantel; Liver; Patient; Infection; Cancerology; Parasiticide; Lesion; Protection; Molecular adduct; Adduct
• ISSN: 1055-9965; 1538-7755
• DOI: 10.1158/1055-9965.EPI-08-0191

Chronic infection by Opisthorchis viverrini (OV) is a strong risk factor for developing cholangiocarcinoma (CCA). To clarify the involvement of oxidative stress and lipid peroxidation (LPO)–derived DNA damage, the excretion of LPO-derived etheno DNA adducts was measured in urine samples collected from healthy volunteers and OV-infected Thai subjects. 1, N 6 -etheno-2′-deoxyadenosine (εdA) and 3, N 4 -etheno-2′-deoxycytidine (εdC) levels were quantified by immunoprecipitation/high-performance liquid chromatography/fluorescence detection and 32 P-postlabeling TLC. Excreted etheno adduct levels were related to indicators of inflammatory conditions [malondialdehyde (MDA) and nitrate/nitrite levels in urine and plasma alkaline phosphatase (ALP) activity]. Mean εdA and εdC levels were 3 to 4 times higher in urine of OV-infected patients; MDA, nitrate/nitrite, and ALP were also increased up to 2-fold. MDA and ALP were positively related to εdA excretion. Two months after a single dose of the antiparasitic drug Praziquantel, εdA and εdC concentrations in urine of OV-infected subjects were decreased; MDA, nitrate/nitrite, and ALP were concomitantly lowered. We conclude that chronic OV infection through oxidative/nitrative stress leads to increased urinary excretion of the etheno-bridged deoxyribonucleosides, reflecting high LPO-derived DNA damage in vivo . These promutagenic DNA etheno adducts in bile duct epithelial cells may increase the risk of OV-infected patients to later develop CCA. Urinary εdA and εdC levels should be explored ( a ) as noninvasive risk markers for developing opisthorchiasis-related CCA and ( b ) as promising biomarkers to assess the efficacy of preventive and therapeutic interventions. (Cancer Epidemiol Biomarkers Prev 2008;17(7):1658–64)