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

• Verfasst von: Teufel-Schäfer, Ulrike [VerfasserIn]
• Verfasst von: Peccerella, Teresa [VerfasserIn]
• Verfasst von: Engelmann, Guido [VerfasserIn]
• Verfasst von: Bruckner, Thomas [VerfasserIn]
• Verfasst von: Flechtenmacher, Christa [VerfasserIn]
• Verfasst von: Millonig, Gunda [VerfasserIn]
• Verfasst von: Stickel, Felix [VerfasserIn]
• Verfasst von: Hoffmann, Georg F. [VerfasserIn]
• Verfasst von: Schirmacher, Peter [VerfasserIn]
• Verfasst von: Mueller, Sebastian [VerfasserIn]
• Verfasst von: Bartsch, Helmut [VerfasserIn]
• Verfasst von: Seitz, Helmut K. [VerfasserIn]
• Titel: Detection of carcinogenic etheno-DNA adducts in children and adolescents with non-alcoholic steatohepatitis (NASH)
• Verf.angabe: 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
• E-Jahr: 2015
• Jahr: December 2015
• Umfang: 10 S.
• Fussnoten: Gesehen am 30.06.2020
• Titel Quelle: Enthalten in: Hepatobiliary surgery and nutrition
• Ort Quelle: Hong Kong : AME Publishing Co., 2012
• Jahr Quelle: 2015
• Band/Heft Quelle: 4(2015), 6, Seite 426-435
• ISSN Quelle: 2304-389X
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1702913686

Abstract

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.