Related Experiment Video
Updated: Jul 25, 2026
12:15
Quantification of three DNA Lesions by Mass Spectrometry and Assessment of Their Levels in Tissues of Mice Exposed to Ambient Fine Particulate Matter
Published on: May 29, 2019
Oxidative DNA damage and cardiovascular disease.
1Center for Cancer Pharmacology, 1254 BRB II/III, 421 Curie Bvd., University of Pennsylvania, Philadelphia, PA 19104-6160, USA.
Trends in Cardiovascular Medicine
|November 1, 2001
Summary
Reactive oxygen species generate genotoxic aldehydes that damage DNA. Lipid hydroperoxides contribute to this damage, forming mutagenic DNA adducts, particularly relevant for cardiovascular disease research.
Area of Science:
- Biochemistry
- Molecular Biology
- Toxicology
Background:
- Reactive oxygen species (ROS) induce DNA damage through direct modification or via lipid hydroperoxides.
- Lipid hydroperoxides decompose into alpha,beta-unsaturated aldehyde genotoxins, including 4-oxo-2-nonenal and 4,5-epoxy-2(E)-decenal.
- These aldehydes can be formed through distinct pathways involving radical rearrangement or intermediate hydroperoxides.
Purpose of the Study:
- To investigate the formation of DNA adducts from lipid hydroperoxide-derived genotoxins.
- To identify specific etheno- and ethano-DNA adducts formed by these aldehydes.
- To highlight the potential role of lipid hydroperoxide-mediated DNA damage in cardiovascular diseases.
Main Methods:
- Reaction of genotoxic aldehydes (4-oxo-2-nonenal, 4,5-epoxy-2(E)-decenal) with DNA.
- Identification of DNA adducts using analytical techniques (not specified in abstract).
- Analysis of DNA adducts in human tissue samples.
Main Results:
- 4,5-Epoxy-2(E)-decenal forms etheno-2'-deoxyadenosine adducts, a mutagenic lesion found in human tissues.
- Several novel ethano- and etheno-DNA adducts were identified from the reaction of 4-oxo-2-nonenal with DNA.
- Malondialdehyde forms a propano adduct (M1G-dR) with 2'-deoxyguanosine, distinct from etheno adducts.
Conclusions:
- Lipid hydroperoxides are a significant source of genotoxic aldehydes that modify DNA.
- Specific DNA adducts, like etheno-2'-deoxyadenosine, are biomarkers of exposure in human tissues.
- The implications of lipid hydroperoxide-induced DNA damage in cardiovascular disease warrant further investigation.
Related Concept Videos
02:25Overview of DNA Repair
In order to be passed through generations, genomic DNA must be undamaged and error-free. However, every day, DNA in a cell undergoes several thousand to a million damaging events by natural causes and external factors. Ionizing radiation such as UV rays, free radicals produced during cellular respiration, and hydrolytic damage from metabolic reactions can alter the structure of DNA. Damages caused include single-base alteration, base dimerization, chain breaks, and cross-linkage.
Chemically...
Chemically...
01:35Mutations
Mutations are changes in the sequence of DNA. These changes can occur spontaneously or they can be induced by exposure to environmental factors. Mutations can be characterized in a number of different ways: whether and how they alter the amino acid sequence of the protein, whether they occur over a small or large area of DNA, and whether they occur in somatic cells or germline cells.
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
01:20Radical Autoxidation
The oxidation of an organic compound in the presence of air or oxygen is called autoxidation. For example, cumene reacts with oxygen to form hydroperoxide. Autoxidation involves initiation, propagation, and termination steps. Many organic compounds are susceptible to autoxidation—especially ethers in the presence of oxygen, which form hydroperoxides. Even though this reaction is slow, old ether bottles contain small amounts of peroxide, which leads to laboratory explosions during ether...
01:38Nucleotide Excision Repair
DNA Distortion and Damage
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
01:30Coronary Artery Disease I: Introduction
Coronary Artery Disease (CAD): An Overview with Scientific InsightsCoronary Artery Disease (CAD), often referred to as C-A-D, is a prevalent blood vessel disorder classified under the broader category of atherosclerosis. Atherosclerosis is a pathological process characterized by the hardening and narrowing of arteries due to the accumulation of atherosclerotic plaques. These plaques are composed of cholesterol, fatty substances, inflammatory cells, calcium, and fibrin, reducing blood flow to...
01:30Spontaneous and Induced Mutations
Spontaneous mutations arise infrequently during DNA replication due to errors in the process. A key factor behind these errors is tautomeric shifts in nitrogenous bases, where bases transition from keto to enol forms or amino to imino forms. This shift can alter base-pairing rules, leading to mutations. Additionally, reactive oxygen species (ROS) arising from aerobic metabolism can damage DNA, resulting in depurination (loss of a purine base) or depyrimidination (loss of a pyrimidine base).