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Langenbeck's Archives of Surgery
Published in: Langenbeck's Archives of Surgery 5/2006

01-09-2006 | New Surgical Horizons

Chronic inflammation and oxidative stress in the genesis and perpetuation of cancer: role of lipid peroxidation, DNA damage, and repair

Authors: Helmut Bartsch, Jagadeesan Nair

Published in: Langenbeck's Archives of Surgery | Issue 5/2006

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Abstract

Background and aims

Chronic inflammation, induced by biological, chemical, and physical factors, was associated with increased risk of human cancer at various sites. Chronic inflammatory processes induce oxidative/nitrosative stress and lipid peroxidation (LPO), thereby generating excess reactive oxygen species (ROS), reactive nitrogen species (RNS), and DNA-reactive aldehydes. Miscoding etheno- and propano-modified DNA bases are generated inter alia by reaction of DNA with these major LPO products. Steady-state levels of LPO-derived (etheno-) DNA adducts in organs affected by persistent inflammatory processes were investigated as potential lead markers for assessing progression of inflammatory cancer-prone diseases.

Results

Using ultrasensitive and specific detection methods for the analysis of human tissues, cells, and 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. Patients with alcohol-related liver diseases showed excess hepatic DNA damage progressively increasing from hepatitis, fatty liver, to liver cirrhosis. Ethenodeoxyadenosine excreted after DNA repair in urine of hepatitis B virus-related chronic hepatitis and liver cirrhosis patients was increased up to 90-fold. Putative mechanisms that may control DNA damage in inflamed tissues including impaired or imbalanced DNA repair pathways are reviewed.

Conclusion

Persistent oxidative/nitrosative stress and excess LPO are induced by inflammatory processes in a self-perpetuating process and cause progressive accumulation of DNA damage in target organs. Together with deregulation of cell homeostasis, the resulting genetic changes act as driving force in chronic inflammation-associated human disease pathogenesis. Thus steady-state levels of DNA damage caused by ROS, RNS, and LPO end products provide promising molecular signatures for risk prediction and potential targets and biomarkers for preventive measures.
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Metadata
Title
Chronic inflammation and oxidative stress in the genesis and perpetuation of cancer: role of lipid peroxidation, DNA damage, and repair
Authors
Helmut Bartsch
Jagadeesan Nair
Publication date
01-09-2006
Publisher
Springer-Verlag
Published in
Langenbeck's Archives of Surgery / Issue 5/2006
Print ISSN: 1435-2443
Electronic ISSN: 1435-2451
DOI
https://doi.org/10.1007/s00423-006-0073-1

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