Abstract |
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.
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Authors | Somkid Dechakhamphu, Somchai Pinlaor, Paiboon Sitthithaworn, Jagadeesan Nair, Helmut Bartsch, Puangrat Yongvanit |
Journal | Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
(Cancer Epidemiol Biomarkers Prev)
Vol. 19
Issue 1
Pg. 310-8
(Jan 2010)
ISSN: 1538-7755 [Electronic] United States |
PMID | 20056652
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anthelmintics
- DNA Adducts
- Nitrates
- Nitrites
- 8-epi-prostaglandin F2alpha
- Malondialdehyde
- Praziquantel
- Dinoprost
- alpha-Tocopherol
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Topics |
- Animals
- Anthelmintics
(therapeutic use)
- Bile Duct Neoplasms
(blood, parasitology, prevention & control)
- Bile Ducts, Intrahepatic
(metabolism, parasitology)
- Cholangiocarcinoma
(blood, parasitology, prevention & control)
- DNA Adducts
(blood, drug effects)
- Dinoprost
(analogs & derivatives, blood)
- Female
- Humans
- Leukocytes
(drug effects)
- Lipid Peroxidation
(drug effects)
- Male
- Malondialdehyde
(blood)
- Middle Aged
- Nitrates
(blood)
- Nitrites
(blood)
- Opisthorchiasis
(blood, drug therapy)
- Opisthorchis
- Oxidative Stress
(drug effects, physiology)
- Praziquantel
(therapeutic use)
- alpha-Tocopherol
(blood)
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