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Urinary 8-Oxo-7,8-Dihydro-2'-Deoxyguanosine in Patients with Parasite Infection and Effect of Antiparasitic Drug in Relation to Cholangiocarcinogenesis

Departments of ¹ Biochemistry, ² Parasitology, and ³ Surgery, ⁴ Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand; ⁵ Bureau of General Communicable Diseases, Department of Disease Control, Ministry of Public Health, Thailand; ⁶ Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Tsu, Mie, Japan; and ⁷ Faculty of Health Science, Suzuka University of Medical Science, Suzuka, Mie, Japan

Requests for reprints: Shosuke Kawanishi, Faculty of Health Science, Suzuka University of Medical Science, Suzuka, Mie 510-0293, Japan. Phone: 81-59-381-2388; Fax: 81-59-381-2386. E-mail: kawanisi{at}suzuka-u.ac.jp

Parasite infection of Opisthorchis viverrini is a major risk factor for cholangiocarcinoma. Our previous immunohistochemical studies showed that O. viverrini infection induced oxidative DNA lesions in the bile duct epithelium during cholangiocarcinoma development. The current study assessed the levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), an oxidative DNA lesion, in the urine and leukocytes of O. viverrini–infected subjects and cholangiocarcinoma patients. Forty-nine O. viverrini–infected patients, 55 cholangiocarcinoma patients, and 17 healthy controls were enrolled in the study. We measured 8-oxodG levels in the urine and leukocytes of these subjects using an electrochemical detector coupled to high-performance liquid chromatography. O. viverrini–infected patients were assessed before treatment and 2 months and 1 year after praziquantel treatment. Urinary 8-oxodG levels were significantly higher in cholangiocarcinoma patients (6.83 ± 1.00 µg/g creatinine) than in O. viverrini–infected patients (4.45 ± 0.25 µg/g creatinine; P < 0.05) and healthy subjects (3.03 ± 0.24 µg/g creatinine; P < 0.01) and higher in O. viverrini–infected subjects than in healthy subjects (P < 0.01). The urinary 8-oxodG levels in O. viverrini–infected patients significantly decreased 2 months after praziquantel treatment and were comparable with levels in healthy subjects 1 year after treatment. Urinary 8-oxodG levels were significantly correlated with leukocyte 8-oxodG levels, plasma nitrate/nitrite levels, and aspartate aminotransferase activity. In conclusion, this study, in addition to our previous studies, indicates that 8-oxodG formation by parasite infection may play an important role in cholangiocarcinoma development. Urinary 8-oxodG may be a useful biomarker to monitor not only infection but also carcinogenesis. (Cancer Epidemiol Biomarkers Prev 2008;17(3):518–24)