Accumulation of lipid peroxidation-derived DNA lesions

• Verfasst von: Bartsch, Helmut [VerfasserIn]
• Verfasst von: Nair, Jagadeesan [VerfasserIn]
• Titel: Accumulation of lipid peroxidation-derived DNA lesions
• Titelzusatz: Potential lead markers for chemoprevention of inflammation-driven malignancies
• Verf.angabe: Helmut Bartsch, Jagadeesan Nair
• E-Jahr: 2005
• Jahr: 15 August 2005
• Umfang: 11 S.
• Fussnoten: Gesehen am 27.11.2020
• Titel Quelle: Enthalten in: Mutation research / Fundamental and molecular mechanisms of mutagenesis
• Ort Quelle: Amsterdam : Elsevier, 1964
• Jahr Quelle: 2005
• Band/Heft Quelle: 591(2005), Seite 34-44
• ISSN Quelle: 1879-2871
• DOI: doi:10.1016/j.mrfmmm.2005.04.013
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: 4-Hydroxy-2-nonenal
• Sach-SW: Chronic inflammation
• Sach-SW: Etheno-DNA adducts
• Sach-SW: Human cancer chemoprevention
• Sach-SW: Impaired DNA-repair
• Sach-SW: Lipid peroxidation
• K10plus-PPN: 1741321239

Abstract

Chronic inflammatory processes produce an excess of ROS and DNA-reactive aldehydes from lipid peroxidation (LPO), such as trans-4-hydroxy-2-nonenal (HNE) and malondialdehyde (MDA), which can modify cellular macromolecules and drive to malignancy. Etheno-modified DNA bases are generated inter alia by reaction of DNA with the major LPO product, HNE. We are investigating steady-state levels of etheno-DNA adducts in organs with diseases related to persistent inflammatory processes that can lead to malignancies. We have developed ultrasensitive and specific methods for the detection of etheno-DNA base adducts in human tissues and in urine. Etheno-DNA adduct levels were found to be significantly elevated in the affected organs of subjects with chronic pancreatitis, ulcerative colitis and Crohn's disease. When patients with alcohol abuse-related hepatitis, fatty liver, fibrosis and cirrhosis were compared with asymptomatic livers, excess hepatic DNA damage was seen in the three latter patient groups. Etheno-deoxyadenosine excreted in urine was measured in HBV-infected patients diagnosed with chronic hepatitis, cirrhosis and hepatocellular carcinoma. As compared to controls, these patients had up to 90-fold increased urinary levels. Impaired or imbalanced DNA-repair pathways may influence the steady-state levels of etheno-DNA adducts in inflamed tissues. In conclusion, etheno-DNA adducts may serve as potential lead markers for assessing progression of inflammatory cancer-prone diseases. If so, the efficacy of human chemopreventive interventions for malignant disease prevention could be verified.