Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
Cancer Epidemiol Biomarkers Prev. 2010 Jan;19(1):310-8. doi: 10.1158/1055-9965.EPI-09-0849.
Chronic infection by the liver fluke Opisthorchis viverrini is a strong risk factor for cholangiocarcinoma. To clarify the involvement of oxidative stress and lipid peroxidation-derived DNA damage, etheno (epsilon)-DNA adducts (epsilondA, epsilondC) in WBC and plasma alpha-tocopherol were measured in samples collected from O. viverrini-infected Thai patients (n = 50) and healthy noninfected volunteers (n = 20). epsilondA and epsilondC levels were three to five times higher (P < 0.001) in infected patients than in controls; O. viverrini infection also increased two to three times in the plasma inflammatory indicators, 8-isoprostane, malondialdehyde, and nitrate/nitrite. Mean plasma alpha-tocopherol levels were two times lower in patients than in healthy controls (P < 0.001). Two months after a single dose to infected patients of the antiparasitic drug praziquantel, epsilondA and epsilondC levels in WBC were decreased to control level (P < 0.03); plasma 8-isoprostane, malondialdehyde, nitrate/nitrite, and alkaline phosphatase (ALP) were concomitantly lowered. epsilondA and epsilondC levels in WBC were positively correlated with plasma 8-isoprostane, malondialdehyde, and nitrate/nitrite levels and ALP activity, whereas plasma alpha-tocopherol levels showed inverse correlations. We conclude that chronic O.viverrini infection induces an accumulation of lipid peroxidation-derived DNA damage through oxidative/nitrative stress, which is lowered by the plasma alpha-tocopherol and by antiparasitic drug therapy. Etheno adducts in WBC and urine should be explored as a risk marker for opisthorchiasis-related cholangiocarcinoma, and to assess the efficacy of preventive and therapeutic interventions.
肝片形吸虫（Opisthorchis viverrini）慢性感染是胆管癌的一个重要危险因素。为了阐明氧化应激和脂质过氧化衍生的 DNA 损伤的参与，我们在采集的来自肝片形吸虫感染的泰国患者（n = 50）和健康未感染者（n = 20）的白细胞（WBC）和血浆α-生育酚样本中测量了乙氧（epsilon）-DNA 加合物（epsilon dA，epsilon dC）。与对照组相比，感染患者的 epsilon dA 和 epsilon dC 水平高出三到五倍（P < 0.001）；肝片形吸虫感染还使血浆炎症指标 8-异前列腺素、丙二醛和硝酸盐/亚硝酸盐增加了两到三倍。与健康对照组相比，患者的平均血浆α-生育酚水平低两倍（P < 0.001）。在给感染患者单次服用驱虫药吡喹酮两个月后，WBC 中的 epsilon dA 和 epsilon dC 水平降低至对照组水平（P < 0.03）；同时降低了血浆 8-异前列腺素、丙二醛、硝酸盐/亚硝酸盐和碱性磷酸酶（ALP）。WBC 中的 epsilon dA 和 epsilon dC 水平与血浆 8-异前列腺素、丙二醛和硝酸盐/亚硝酸盐水平以及 ALP 活性呈正相关，而血浆α-生育酚水平则呈负相关。我们的结论是，慢性肝片形吸虫感染通过氧化/硝化应激引起脂质过氧化衍生的 DNA 损伤的积累，这种积累可以通过血浆α-生育酚和抗寄生虫药物治疗来降低。WBC 和尿液中的乙氧加合物应作为与肝片形吸虫相关的胆管癌的风险标志物进行探索，并评估预防和治疗干预的效果。
