Langenbeck's Archives of Surgery

, Volume 391, Issue 5, pp 499–510 | Cite as

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

  • Helmut BartschEmail author
  • Jagadeesan Nair
New Surgical Horizons


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.


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.


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.


Chronic inflammation Oxidative stress DNA damage Impaired DNA repair Human cancers 



The authors greatly acknowledge the contributions and collaborative efforts by X. Sun, A. Frank, N. Frank, Y. Yang, and late C. Ditrich (DKFZ, Heidelberg); A. Barbin and Y Guichard (Lyon, France); G. Fürstenberger (DKFZ, Heidelberg); S. Tannenbaum and G. Wogan (Cambridge, USA); G. Winde (Herford, Germany); P. Srivanatakul (Bangkok, Thailand); F. Gansauge and H. Beger (Ulm, Germany); P. Dolora (Florence, Italy); and H.K. Seitz (Heidelberg, Germany). S. Fuladdjusch is thanked for excellent secretarial help. Work was in part supported by EU contracts ENV4-CT97-0505 and QLK4-CT2000-00286.


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© Springer-Verlag 2006

Authors and Affiliations

  1. 1.Division of Toxicology and Cancer Risk FactorsGerman Cancer Research Center (DKFZ)HeidelbergGermany

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