Accumulation of lipid peroxidation-derived DNA lesions: Potential lead markers for chemoprevention of inflammation-driven malignancies
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...
Saved in:
| Main Authors: | , |
|---|---|
| Format: | Article (Journal) |
| Language: | English |
| Published: |
15 August 2005
|
| In: |
Mutation research. Fundamental and molecular mechanisms of mutagenesis
Year: 2005, Volume: 591, Pages: 34-44 |
| ISSN: | 1879-2871 |
| DOI: | 10.1016/j.mrfmmm.2005.04.013 |
| Online Access: | Verlag, Volltext: https://doi.org/10.1016/j.mrfmmm.2005.04.013 Verlag, Volltext: http://www.sciencedirect.com/science/article/pii/S0027510705002836 
|
| Author Notes: | Helmut Bartsch, Jagadeesan Nair |
| Summary: | 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. |
|---|---|
| Item Description: | Gesehen am 27.11.2020 |
| Physical Description: | Online Resource |
| ISSN: | 1879-2871 |
| DOI: | 10.1016/j.mrfmmm.2005.04.013 |