What causes bulky adducts in DNA?
Large bulky adducts are produced or formed from many of the large organic carcinogenic compounds, including PAHs, aromatic amines, and aflatoxin. A number of factors can influence what adducts are formed.
Why is DNA adducts bad?
If not repaired, the DNA adducts can interfere with DNA transcription and replication, and induce mutations. The ability of DNA adducts to induce mutations by site-specific mutagenesis in vitro or as observed in cell studies have revealed different mutational spectra for different types of DNA adducts.
What are bulky DNA adducts?
Bulky DNA adducts are markers of exposure to genotoxic aromatic compounds, which reflect an individual’s ability to metabolically activate carcinogens and to repair DNA damage. Polycyclic aromatic hydrocarbons (PAH) represent a major class of carcinogens that are capable of forming such adducts.
How do DNA adducts cause mutations?
DNA adducts are a form of DNA damage caused by covalent attachment of a chemical moiety to DNA. Adducts that are not removed by the cell can cause mutations that may give rise to cancer. They are frequently used as biomarkers for chemical hazard exposure or cancer therapy efficacy.
How are bulky adducts to DNA removed?
Large distortions caused by bulky DNA adducts (eg, BPDE-dG and 4ABP-dC) are recognized (XPA) and removed by endonucleases (XPF, XPG, FEN).
Why do small chemical adducts on the DNA cause mutations?
When a chemical binds to DNA, the DNA becomes damaged, and proper and complete replication cannot occur to make the normal intended cell. This could be the start of a mutation, or mutagenesis.
How are DNA adducts removed?
Based on a recent report by our group, the aim of this study was to test the hypothesis that DNA adducts can be removed by means of one or more of the following three intervention programmes: intermittent whole-body hyperthermia; detoxification; and cell repair.
What damage mutagens can cause to DNA and proteins?
Cigarettes and tobacco products contain chemicals referred to as carcinogens, which are mutagens that are also known to cause cancer. All cancer cells have DNA mutations, and it is the carcinogens that cause the mutations. Carcinogens cause mutations by damaging the way the cell repairs DNA or makes proteins.
What is damaged DNA?
DNA damage is a change in the basic structure of DNA that is not itself replicated when the DNA is replicated. A DNA damage can be a chemical addition or disruption to a base of DNA (creating an abnormal nucleotide or nucleotide fragment) or a break in one or both chains of the DNA strands.
Can DNA adducts be repaired?
Tolerance and Repair of Lipid Peroxide DNA Adducts Although this type of lesion can be repaired by NER [106,249], such a repair is not very efficient. An alternative pathway to deal with this lesion is a replicative bypass by specialized DNA polymerase through the process of translesion DNA synthesis (TLS).
How do adducts form?
An adduct (from the Latin adductus, “drawn toward” alternatively, a contraction of “addition product”) is a product of a direct addition of two or more distinct molecules, resulting in a single reaction product containing all atoms of all components. Adducts often form between Lewis acids and Lewis bases.
What repair mechanism would remove the bulky DNA adducts or lesions generated by cisplatin and what type of radiation can be tolerated by cells resistant to cisplatin?
Nucleotide excision repair. The bulky DNA adducts generated by cisplatin are mainly repaired by the NER pathway (Figure 3A).
Why do bulky DNA adducts occur in DNA?
Bulky DNA adducts represent exposure to PAH and other aromatic compounds after the action of metabolizing enzymes; they are in steady-state if exposure is constant. In addition, they also reflect the action of DNA repair enzymes and, thus, of individual susceptibility.
Why are bulky DNA adducts a biomarker for cancer?
“Bulky” DNA adducts represent an integrated marker of exposure to aromatic compounds, and of the ability of the individual to metabolically activate carcinogens and to repair DNA damage. The level of bulky adducts in WBCs has been shown to correlate with external exposure to PAHs 3 in a few investigations.
Who is at higher risk for DNA adducts?
Women smokers may be at higher risk of developing lung cancer for a given tobacco exposure and women also seem to accumulate aromatic/hydrophobic DNA adducts at a faster rate than men. 168 (See Chapter 52 .) DNA adducts are covalent interactions between reactive carcinogen chemical species and DNA (usually genomic).
Can a DNA adduct cause a double strand break?
DNA strand breaks can result from DNA adducts and can arise either through (1) direct alkylation of the phosphodiester backbone leading to chemical cleavage of the backbone or (2) excision repair mechanisms that are incomplete during DNA replication. Strand scission can lead to double-strand breaks, recombination, or loss of heterozyogosity.