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High excretion of etheno adducts in liver fluke-infected patients: protection by praziquantel against DNA damage.

Abstract
Chronic infection by Opisthorchis viverrini (OV) is a strong risk factor for developing cholangiocarcinoma (CCA). To clarify the involvement of oxidative stress and lipid peroxidation (LPO)-derived DNA damage, the excretion of LPO-derived etheno DNA adducts was measured in urine samples collected from healthy volunteers and OV-infected Thai subjects. 1,N(6)-etheno-2'-deoxyadenosine (epsilondA) and 3,N(4)-etheno-2'-deoxycytidine (epsilondC) levels were quantified by immunoprecipitation/high-performance liquid chromatography/fluorescence detection and (32)P-postlabeling TLC. Excreted etheno adduct levels were related to indicators of inflammatory conditions [malondialdehyde (MDA) and nitrate/nitrite levels in urine and plasma alkaline phosphatase (ALP) activity]. Mean epsilondA and epsilondC levels were 3 to 4 times higher in urine of OV-infected patients; MDA, nitrate/nitrite, and ALP were also increased up to 2-fold. MDA and ALP were positively related to epsilondA excretion. Two months after a single dose of the antiparasitic drug Praziquantel, epsilondA and epsilondC concentrations in urine of OV-infected subjects were decreased; MDA, nitrate/nitrite, and ALP were concomitantly lowered. We conclude that chronic OV infection through oxidative/nitrative stress leads to increased urinary excretion of the etheno-bridged deoxyribonucleosides, reflecting high LPO-derived DNA damage in vivo. These promutagenic DNA etheno adducts in bile duct epithelial cells may increase the risk of OV-infected patients to later develop CCA. Urinary epsilondA and epsilondC levels should be explored (a) as noninvasive risk markers for developing opisthorchiasis-related CCA and (b) as promising biomarkers to assess the efficacy of preventive and therapeutic interventions.
AuthorsSomkid Dechakhamphu, Puangrat Yongvanit, Jagadeesan Nair, Somchai Pinlaor, Paiboon Sitthithaworn, Helmut Bartsch
JournalCancer 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. 17 Issue 7 Pg. 1658-64 (Jul 2008) ISSN: 1055-9965 [Print] United States
PMID18628417 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Anthelmintics
  • DNA Adducts
  • Deoxyadenosines
  • Deoxycytidine
  • Praziquantel
  • 1,N(6)-ethenodeoxyadenosine
  • 3,N(4)-ethenodeoxycytidine
Topics
  • Adult
  • Animals
  • Anthelmintics (pharmacology)
  • Bile Duct Neoplasms (epidemiology, etiology, prevention & control)
  • Bile Ducts, Intrahepatic
  • Cholangiocarcinoma (epidemiology, etiology, prevention & control)
  • Chromatography, High Pressure Liquid
  • DNA Adducts (urine)
  • DNA Damage (drug effects)
  • Deoxyadenosines (urine)
  • Deoxycytidine (analogs & derivatives, urine)
  • Feces (parasitology)
  • Female
  • Humans
  • Immunoprecipitation
  • Incidence
  • Male
  • Middle Aged
  • Opisthorchiasis (complications, epidemiology, urine)
  • Opisthorchis (isolation & purification)
  • Oxidative Stress
  • Praziquantel (pharmacology)
  • Risk Factors
  • Thailand (epidemiology)

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