Urinary 8-oxo-7,8-dihydro-2′-deoxyguanosine in patients with parasite infection and effect of antiparasitic drug in relation to cholangiocarcinogenesis
Urinary 8-oxo-7,8-dihydro-2′-deoxyguanosine in patients with parasite infection and effect of antiparasitic drug in relation to cholangiocarcinogenesis
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DOI：
10.1158/1055-9965.epi-07-2717
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发表时间：
2008-03-01
影响因子：
3.8
通讯作者：
Kawanishi, Shosuke
中科院分区：
文献类型：
--
作者：
Thanan, Raynoo;Murata, Mariko;Kawanishi, Shosuke
间日圆锥虫寄生虫感染是胆管癌的主要危险因素。我们先前的免疫组织化学研究表明，在胆管癌的发生发展过程中，活体奥氏菌感染导致胆管上皮细胞DNA氧化损伤。本研究评估了8-氧-7，8-二氢-2‘-脱氧鸟苷(8-oxodG)的水平，8-oxodG是一种氧化性DNA损伤，在华支睾吸虫感染者和胆管癌患者的尿液和白细胞中的水平。49名感染华支睾吸虫的患者、55名胆管细胞癌患者和17名健康对照参加了研究。我们使用与高效液相色谱相结合的电化学检测器测量了这些受试者尿液和白细胞中的8-oxodG水平。在吡喹酮治疗前、治疗后2个月和1年对感染新城疫原虫的患者进行评估。胆管癌组尿8-oxodG水平(6.83+/-1.00 mU/g肌酐)显著高于肝吸虫感染者(4.45+/-0.25 mU/g肌酐；p<；0.05)和健康对照组(3.03+/-0.24 mg/g肌酐；p<；0.01)。在吡喹酮治疗2个月后，弧菌感染患者的尿8-oxodG水平显著下降，治疗1年后与健康人水平相当。尿8-oxodG水平与白细胞8-oxodG水平、血浆硝酸盐/亚硝酸盐水平及天冬氨酸氨基转移酶活性显著相关。综上所述，除了我们之前的研究外，这项研究还表明，寄生虫感染形成的8-oxodG可能在胆管癌的发生发展中起重要作用。尿8-oxodG可能是一种有用的生物标志物，不仅可以监测感染，还可以监测肿瘤的发生。
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 I year after praziquantel treatment. Urinary 8-oxodG levels were significantly higher in cholangiocarcinoma patients (6.83+/- 1.00 mu g/g creatinine) than in O. viverrint-infected patients (4.45 +/- 0.25 mu g/g creatinine; p < 0.05) and healthy subjects (3.03 +/- 0.24 mu g/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. vivenini-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.