title: Oxidative and nitrative DNA damage: key events in opisthorchiasis-induced carcinogenesis.
abstract: Chronic inflammation induced by liver fluke (Opisthorchis viverrini) infection is the major risk factor for cholangiocarcinoma (CCA) in Northeastern Thailand. Increased levels of proinflammatory cytokines and nuclear factor kappa B that control cyclooxygenase-2 and inducible nitric oxide activities, disturb the homeostasis of oxidants/anti-oxidants and DNA repair enzymes, all of which appear to be involved in O. viverrini-associated inflammatory processes and CCA. Consequently oxidative and nitrative stress-related cellular damage occurs due to the over production of reactive oxygen and nitrogen species in inflamed target cells. This is supported by the detection of high levels of oxidized DNA and DNA bases modified by lipid peroxidation products in both animal and human tissues affected by O. viverrini-infection. Treatment of opisthorchiasis patients with praziquantel, an anti- trematode drug was shown to reduce inflammation-mediated tissue damage and carcinogenesis. The principal mechanisms that govern the effects of inflammation and immunity in liver fluke-associated cholangiocarcinogenesis are reviewed. The validity of inflammation-related biomolecules and DNA damage products to serve as predictive biomarkers for disease risk evaluation and intervention is discussed.
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand. puangrat@kku.ac.th
authors.forename: Puangrat
authors.initials: P
authors.lastname: Yongvanit
authors.forename: Somchai
authors.initials: S
authors.lastname: Pinlaor
authors.forename: Helmut
authors.initials: H
authors.lastname: Bartsch
mesh_terms: D000818:Animals; D000871:Anthelmintics / Q000627:therapeutic use; D001650:Bile Duct Neoplasms / Q000276:immunology / Q000469:parasitology / Q000473:pathology / Q000503:physiopathology*; D001653:Bile Ducts, Intrahepatic / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D018281:Cholangiocarcinoma / Q000276:immunology / Q000469:parasitology / Q000473:pathology / Q000503:physiopathology*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004249:DNA Damage; D004195:Disease Models, Animal; D006801:Humans; D015227:Lipid Peroxidation; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009889:Opisthorchiasis / Q000150:complications* / Q000188:drug therapy / Q000469:parasitology* / Q000473:pathology; D009891:Opisthorchis / Q000502:physiology*; D018384:Oxidative Stress; D011223:Praziquantel / Q000627:therapeutic use; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012307:Risk Factors; D012377:Rodentia; D013785:Thailand
chemical_list: D000871:Anthelmintics; D016207:Cytokines; D016328:NF-kappa B; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D011223:Praziquantel; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human