How do oxygen radicals damage DNA?

Oxygen radicals generated during reduction of O2 can attack DNA bases or deoxyribose residues to produce damaged bases or strand breaks (2). Alternatively, oxygen radicals can oxidize lipid or protein molecules to generate intermediates that react with DNA to form adducts (3).

How does ROS cause DNA damage?

Cells have developed various enzymatic and nonenzymatic defense systems to control excited oxygen species, however, a certain fraction escapes the cellular defense and may cause permanent or transient damage to nucleic acids within the cells, leading to such events as DNA strand breakage and disruption of Ca2+ …

How do free radicals affect DNA?

Free radicals are produced in cells by cellular metabolism and by exogenous agents. These species react with biomolecules in cells, including DNA. The resulting damage to DNA, which is also called oxidative damage to DNA, is implicated in mutagenesis, carcinogenesis, and aging.

What causes DNA damage?

DNA damage can be subdivided into two types: (1) endogenous damage caused by reactive oxygen species (ROS) that are derived from metabolic byproducts and (2) exogenous damage caused by radiation (UV, X-ray, gamma), hydrolysis, plant toxins, and viruses.

What causes lipid peroxidation?

Lipid peroxidation is a process generated naturally in small amounts in the body, mainly by the effect of several reactive oxygen species (hydroxyl radical, hydrogen peroxide etc.). It can also be generated by the action of several phagocytes.

How does lipid peroxidation damage cells?

Lipid peroxidation is the chain of reactions of oxidative degradation of lipids. It is the process in which free radicals “steal” electrons from the lipids in cell membranes, resulting in cell damage. This process proceeds by a free radical chain reaction mechanism.

What are the stages of lipid peroxidation?

The overall process of lipid peroxidation consists of three steps: initiation, propagation, and termination [31, 36, 37].

What components of DNA are subject to oxidative damage?

Oxidized bases in DNA When DNA undergoes oxidative damage, two of the most common damages change guanine to 8-hydroxyguanine or to 2,6-diamino-4-hydroxy-5-formamidopyrimidine.

What are three ways that DNA gets damaged?

DNA bases can be damaged by: (1) oxidative processes, (2) alkylation of bases, (3) base loss caused by the hydrolysis of bases, (4) bulky adduct formation, (5) DNA crosslinking, and (6) DNA strand breaks, including single and double stranded breaks. An overview of these types of damage are described below.

What chemicals can damage DNA?

This review predominantly concentrates on DNA damage induced by the following carcinogens: polycyclic aromatic hydrocarbons, heterocyclic aromatic amines, mycotoxins, ultraviolet light, ionising radiation, aristolochic acid, nitrosamines and particulate matter.

What is the purpose of lipid peroxidation?

Lipid peroxidation-derived aldehydes play a major role in human health and disease as they act as important signaling intermediates in modulating cellular physiological function via regulating various transcription factors (Fig. 32.6).

What triggers lipid peroxidation?

3.1 Overview. Lipid peroxidation is the core reaction of ferroptosis, which is caused by the attack of oxidants on lipids. Due to the production of lipid peroxyl radicals, hydroperoxides, and various oxidation products, uncontrolled lipid peroxidation leads to membrane rupture and cell death.

What are some factors that can cause DNA damage?

Which of the following is highly associated with the DNA damage?

DNA can be damaged via environmental factors as well. Environmental agents such as UV light, ionizing radiation, and genotoxic chemicals. Replication forks can be stalled due to damaged DNA and double strand breaks are also a form of DNA damage.

Where does lipid peroxidation occur?

Oxidative breakdown of biological phospholipids occurs in most cellular membranes including mitochondria, microsomes, peroxisomes and plasma membrane. The toxicity of lipid peroxidation products in mammals generally involves neurotoxicity, hepatotoxicity and nephrotoxicity (Boveris et al., 2008).

What are the 4 causes of mutations?

Mutations can result from errors in DNA replication during cell division, exposure to mutagens or a viral infection. Germline mutations (that occur in eggs and sperm) can be passed on to offspring, while somatic mutations (that occur in body cells) are not passed on.

What are the three major types of damage that occur to DNA?

How is DNA damaged by lipid peroxidation repaired?

It is repaired by the nucleotide excision repair pathway. Lipid peroxidation appears to be a major source of endogenous DNA damage in humans that may contribute significantly to cancer and other genetic diseases linked to lifestyle and dietary factors.

Can antioxidants ameliorate radiation-related toxicological damage?

Many of the types of damage seen after irradiation can be ameliorated by antioxidants. This review will outline a number of radiation-related toxicological processes and discuss the role antioxidants might play in affecting these processes in terms of the likely cellular types or compartments in which an antioxidant is employed.

What are the carbonyl products of lipid peroxidation?

One of the most abundant carbonyl products of lipid peroxidation is malondialdehyde (MDA), which also is generated as a side-product of prostaglandin biosynthesis. It reacts with DNA to form adducts to deoxyguanosine, deoxyadenosine, and deoxycytidine.

Are antioxidants radioprotective at the cellular level?

There is a large volume of data on the radioprotective effects of antioxidants at the cellular level, especially at the level of nuclear DNA, where the radical scavenging by the antioxidant protects this and other sensitive cellular targets.

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