Exocyclic DNA Adducts as Oxidative Stress Markers in Colon Carcinogenesis: Potential Role of Lipid Peroxidation, Dietary Fat and Antioxidants
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Helmut Bartsch
Abstract
Molecular pathways to colorectal cancer involve multiple genetic changes, whereby extensive oxyradical damage causes mutations in cancerrelated genes and leads to a cycle of cell death and regeneration. Besides direct oxidative DNAdamage, reactive oxygen and nitrogen species can induce etheno ()DNA adducts mainly via trans-4-hydroxy-2-nonenal, generated as the major aldehyde by lipid peroxidation (LPO) of ω-6 PUFAs. Patients with familial adenomatous polyposis (FAP) develop multiple colorectal adenomas. In affected tissues increased LPO could be triggered due to increased arachidonic acid metabolism as a result of elevated cyclooxygenases. Our studies demonstrated an increased DNA adduct level in affected colon epithelia of FAP patients. DNA adducts are promutagenic and can cause genomic instability that drives colorectal adenoma to malignancy. We have further investigated the potential chemopreventive properties of olive oil and its polyphenolic components. Mediterranean diet, of which olive oil is a major fatty acid source, has protective effects against human breast and colorectal cancers. Olive oil extracts and the newly identified lignan fractions showed high antioxidant capacity in vitro. As DNA adducts are biomarkers for oxidative stress and LPO induced DNA damage, they can verify the efficacy of newly identified antioxidants, e.g. from olive oil, as chemopreventive agents against colon carcinogenesis.
Copyright © 2002 by Walter de Gruyter GmbH & Co. KG
Articles in the same Issue
- Highlight: Environmental Mutagenesis
- DNA Double-Strand Break Repair by Homologous Recombination
- An Overview of the Analysis of DNA Methylation in Mammalian Genomes
- Methylation of the RASSF1A Gene in Human Cancers
- Exocyclic DNA Adducts as Oxidative Stress Markers in Colon Carcinogenesis: Potential Role of Lipid Peroxidation, Dietary Fat and Antioxidants
- DNA Polymorphisms as Modulators of Genotoxicity and Cancer
- Recent Aspects of Oxidative DNA Damage: Guanine Lesions, Measurement and Substrate Specificity of DNA Repair Glycosylases
- The Bacterial Regulatory Protein H-NS A Versatile Modulator of Nucleic Acid Structures
- Molecular Mechanisms of Nickel Carcinogenesis
- DNA Binding Properties of the Yeast Msh2-Msh6 and Mlh1-Pms1 Heterodimers
- N-Hydroxyarylamine O-Acetyltransferase-Deficient Escherichia coli Strains Are Resistant to the Mutagenicity of Nitro Compounds
- Functional Genomics of C190T Single Nucleotide Polymorphism in Human N-Acetyltransferase 2
- Increase in Ceramide Level Alters the Lysosomal Targeting of Cathepsin D prior to Onset of Apoptosis in HT-29 Colon Cancer Cells
- Reconstitution of Transport-Active Multidrug Resistance Protein 2 (MRP2; ABCC2) in Proteoliposomes
- Processing of the Human Transferrin Receptor at Distinct Positions within the Stalk Region by Neutrophil Elastase and Cathepsin G
- Analysis of the Prion Protein in Primates Reveals a New Polymorphism in Codon 226 (Y226F)
- Inducibility of the Streptomyces traRts107-Ptra Expression Cassette in Mycobacterium smegmatis
Articles in the same Issue
- Highlight: Environmental Mutagenesis
- DNA Double-Strand Break Repair by Homologous Recombination
- An Overview of the Analysis of DNA Methylation in Mammalian Genomes
- Methylation of the RASSF1A Gene in Human Cancers
- Exocyclic DNA Adducts as Oxidative Stress Markers in Colon Carcinogenesis: Potential Role of Lipid Peroxidation, Dietary Fat and Antioxidants
- DNA Polymorphisms as Modulators of Genotoxicity and Cancer
- Recent Aspects of Oxidative DNA Damage: Guanine Lesions, Measurement and Substrate Specificity of DNA Repair Glycosylases
- The Bacterial Regulatory Protein H-NS A Versatile Modulator of Nucleic Acid Structures
- Molecular Mechanisms of Nickel Carcinogenesis
- DNA Binding Properties of the Yeast Msh2-Msh6 and Mlh1-Pms1 Heterodimers
- N-Hydroxyarylamine O-Acetyltransferase-Deficient Escherichia coli Strains Are Resistant to the Mutagenicity of Nitro Compounds
- Functional Genomics of C190T Single Nucleotide Polymorphism in Human N-Acetyltransferase 2
- Increase in Ceramide Level Alters the Lysosomal Targeting of Cathepsin D prior to Onset of Apoptosis in HT-29 Colon Cancer Cells
- Reconstitution of Transport-Active Multidrug Resistance Protein 2 (MRP2; ABCC2) in Proteoliposomes
- Processing of the Human Transferrin Receptor at Distinct Positions within the Stalk Region by Neutrophil Elastase and Cathepsin G
- Analysis of the Prion Protein in Primates Reveals a New Polymorphism in Codon 226 (Y226F)
- Inducibility of the Streptomyces traRts107-Ptra Expression Cassette in Mycobacterium smegmatis
