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Detection of carcinogenic etheno-DNA adducts in children and adolescents with non-alcoholic steatohepatitis (NASH)

Background: Carcinogenic exocyclic-DNA adducts like 1,N6-etheno-2'-deoxyadenosine (εdA) are formed through reactive intermediates of 4-hydroxynonenal (4-HNE) or other lipid peroxidation (LPO) products with the DNA bases A, C, methyl-C and G. High levels of hepatic etheno-DNA adducts have been...

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Hauptverfasser: Teufel-Schäfer, Ulrike (VerfasserIn) , Peccerella, Teresa (VerfasserIn) , Engelmann, Guido (VerfasserIn) , Bruckner, Thomas (VerfasserIn) , Flechtenmacher, Christa (VerfasserIn) , Millonig, Gunda (VerfasserIn) , Stickel, Felix (VerfasserIn) , Hoffmann, Georg F. (VerfasserIn) , Schirmacher, Peter (VerfasserIn) , Mueller, Sebastian (VerfasserIn) , Bartsch, Helmut (VerfasserIn) , Seitz, Helmut K. (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: December 2015
In: Hepatobiliary surgery and nutrition
Year: 2015, Jahrgang: 4, Heft: 6, Pages: 426-435
ISSN:2304-389X
Online-Zugang:Verlag, lizenzpflichtig, Volltext: http://hbsn.amegroups.com/article/view/8504
Volltext
Verfasserangaben:Ulrike Teufel, Teresa Peccerella, Guido Engelmann, Thomas Bruckner, Christa Flechtenmacher, Gunda Millonig, Felix Stickel, Georg F. Hoffmann, Peter Schirmacher, Sebastian Mueller, Helmut Bartsch, Helmut K. Seitz
Beschreibung
Zusammenfassung:Background: Carcinogenic exocyclic-DNA adducts like 1,N6-etheno-2'-deoxyadenosine (εdA) are formed through reactive intermediates of 4-hydroxynonenal (4-HNE) or other lipid peroxidation (LPO) products with the DNA bases A, C, methyl-C and G. High levels of hepatic etheno-DNA adducts have been detected in cancer prone liver diseases including alcoholic liver disease (ALD). In ALD εdA levels correlated significantly with cytochrome P-450 2E1 (CYP2E1) expression which is also induced in non-alcoholic steatohepatitis (NASH). We investigated the occurrence of εdA adducts in children with NASH as a DNA damage marker. - Methods: Liver biopsies from 21 children/adolescents with histologically proven NASH were analysed for hepatic fat content, inflammation, and fibrosis. εdA levels in DNA, CYP2E1-expression and protein bound 4-hydroxynonenal (HNE) were semi-quantitatively evaluated by immunohistochemistry. - Results: Among 21 NASH children, εdA levels in the liver were high in 3, moderate in 5, weak in 9 and not elevated in 4 patients. There was a positive correlation between CYP2E1 and protein-bound 4-HNE (r=0.60; P=0.008) and a trend for a positive relationship for CYP2E1 vs. staining intensity of εdA (r=0.45; P=0.06). Inflammatory activity and fibrosis correlated significantly (r=0.49, P=0.023). - Conclusions: Our results demonstrate for the first time the presence of elevated carcinogenic etheno-DNA lesions (εdA) in the majority (17/21) of liver biopsies from young NASH patients. Our data suggest that LPO-derived etheno-adducts are implicated in NASH. Whether these adducts may serve as predictive risk markers in NASH children to develop hepatocellular cancer later in life remains to be investigated.
Beschreibung:Gesehen am 30.06.2020
Beschreibung:Online Resource
ISSN:2304-389X

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