Urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine in patients with parasite infection and effect of antiparasitic drug in relation to cholangiocarcinogenesis.
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 microg/g creatinine) than in O. viverrini-infected patients (4.45 +/- 0.25 mug/g creatinine; P < 0.05) and healthy subjects (3.03 +/- 0.24 microg/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.
Thanan
Raynoo
R
Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
Murata
Mariko
M
Pinlaor
Somchai
S
Sithithaworn
Paiboon
P
Khuntikeo
Narong
N
Tangkanakul
Walaluk
W
Hiraku
Yusuke
Y
Oikawa
Shinji
S
Yongvanit
Puangrat
P
Kawanishi
Shosuke
S
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000704:Analysis of Variance; D000818:Animals; D000871:Anthelmintics / Q000627:therapeutic use*; D001650:Bile Duct Neoplasms / Q000469:parasitology* / Q000652:urine*; D001653:Bile Ducts, Intrahepatic; D014408:Biomarkers, Tumor / Q000652:urine; D016022:Case-Control Studies; D018281:Cholangiocarcinoma / Q000469:parasitology* / Q000652:urine*; D002851:Chromatography, High Pressure Liquid; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000652:urine; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009889:Opisthorchiasis / Q000188:drug therapy* / Q000652:urine*; D009891:Opisthorchis / Q000187:drug effects; D011223:Praziquantel / Q000627:therapeutic use*; D018709:Statistics, Nonparametric; D016896:Treatment Outcome
D000871:Anthelmintics; D014408:Biomarkers, Tumor; D011223:Praziquantel; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine