Detection of highly carcinogenic, exocyclic etheno-DNA-adducts in the liver of children with non-alcoholic fatty liver disease

• Published in: Zeitschrift für Gastroenterologie
• Main Authors: Teufel, U, Engelmann, G, Flechtenmacher, C, Peccerella, T, Millonig, G, Hoffmann, G, Mueller, S, Seitz, HK
• Format: Conference Proceeding
• Language: English; German
• Published: 09.01.2012
• Subjects: NAFLD; 4HNE; CYP2E1
• ISSN: 0044-2771; 1439-7803
• DOI: 10.1055/s-0031-1295833

Exocyclic etheno-DNA-adducts (edA) are highly carcinogenic DNA-lesions which are formed by the reaction of the lipid peroxidation product 4-hydroxynonenal (4HNE) with DNA 1 . Recently, we found a significant correlation between the induction of cytochrome P4502E1 (CYP2E1) and edA in patients with alcoholic liver disease 2 . CYP2E1 is also induced in non-alcoholic fatty liver disease (NAFLD) 3 , a growing liver disease entity in the Western World not only in adults, but also in children and adolescents. Since NAFLD patients have an increased risk for hepatocellular cancer (HCC) 4 , early generation of carcinogenic DNA adducts may be of pathogenetic importance and could serve as a biologic marker for HCC risk. Therefore we wondered whether edA may be generated in young patients with NAFLD. To study this, 20 children (14 males, 6 females) at an age between 9 and 17 years were liver biopsied. Hepatic steatosis, inflammation and fibrosis was evaluated using a scoring system 5 . The diagnosis of NAFLD was based on histology, sonography and blood chemistry. edA, CYP2E1 and 4HNE were evaluated by immunohistochemistry. Three out of 20 children had a significant amount of edA in their livers, while 10 showed moderate amounts, and 7 had almost no detectible adducts. Correlation analysis showed significant correlation between CYP2E1 and 4HNE (r=0.575, P < 0.016). However, there was no correlation between edA and CYP2E1. These data show for the first time the detection of highly carcinogenic DNA-lesion in children with NAFLD. Although these children express high levels of CYP2E1 and 4HNE as signs of induction and lipid peroxidation, no significant correlation was detected between CYP2E1 and DNA-lesions. This is in contrast to adult patients with NAFLD. One explanation for this observation could be that children have still a highly active DNA repair system which repairs altered DNA rapidly. However, further studies are needed to proof this. Literatur: 1. El Ghissassi et al, Biochem Pharmacol 1998;55:1445 2. Wang et al, Hepatology 2009;50:453 3. Weltman et al, Hepatology 1998;27:128 4. Ascha et al,Hepatology 2010;51:1972 5. Kleinert et al, Hepatology 2005;41:1313