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Formation of Covalent DNA Adducts by Enzymatically - JoVE

Quantitation of the specific pyridyloxobutyl DNA adducts in calf thymus DNA treated with a model pyridyloxobutylating agent, 4- (acetoxymethylnitrosamino)-1- (3-pyridyl)-1-butanone (NNKOAc, Scheme 1), demonstrates that HPB-releasing adducts are the major adducts present in pyridyloxobutylated DNA [ 46 Various platinum (II) complexes have been shown to form DNA adducts which decrease gel mobility of DNA fragments due to either stable curvature of the helix axis or increased isotropic flexibility (23, 25 – 30). These results are likely due to the different mode of action between the two chemical classes, as aldehydes are direct acting agents, while alkenylbenzenes require bioactivation to form electrophilic intermediates, which form DNA adducts. TAM-DNA adduct was formed when PAPS, not acetyl-CoA, was used. No TAM-DNA adducts were produced using human N -acetyltransferase I and II. HST antibody inhibited approximately 90% of TAM-DNA adduct formation generated by the cytosol or HST, suggesting that HST is primarily involved in the formation of TAM-DNA adducts.

Due to tautomer formation, the initial adduct may be inherently unstable and undergo cleavage at the 1'-carbon-methylene bond to yield the observed adducts. adducts, such as N7-deoxyguanosine adducts that may be lost through depurination. The administration of radiola-beled material will not permit the detection of changes in endogenous DNA adducts, such as those arising from oxi-dative damage (e.g., 8-oxoguanine) or lipid peroxidation. Finally, due to the costs associated with the preparation of 2019-03-19 These agents have the potential to modify the structure of an individual’s DNA, forming a wide variety of types of DNA damage, known as adducts. Some of these adducts are stressor-specific, such as those formed by the UV in sunlight. Others are more general, and are formed by many different stressors, such as oxidative stress. COMPUTATIONAL STUDIES OF DAMAGED DNA: AN INVESTIGATION OF DNA O-LINKED ADDUCTS FORMED DUE TO EXPOSURE TO PHENOLIC CARCINOGENS MOHADESEH MAJDI YAZDI B.Sc., Sharif University of Technology, 2004 M.Sc., Tarbiat Modares University, 2008 A Thesis Submitted to the School of Graduate Studies of the University of Lethbridge in Partial Fulfillment of the Analysis of DNA adducts formed in vivo can help to improve risk assessment and contribute to better understanding of the mechanisms of chemical carcinogenesis.

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Base pairing always follows Mistakes occasionally do occur spontaneously during DNA replication, causing The single amino acid change caused by the sickle cell mutation reduces the Because of the complementarity of the two strands, having one strand means that it is When two DNA copies are formed, they have an identical sequence of In addition to generation of reactive oxygen species due to redox cycling, the Several studies in vitro indicate that OTA does not form DNA adducts even in the Utvärdera styrkan av miljömässiga kemikalier och läkemedel, vara enzymatiskt bioaktiverade till intermediärer genererar kovalent DNA av T Jurén · 2013 — som för avläggande av medicine doktorsexamen vid Karolinska. Institutet offentligen försvaras i Sal This was done by characterizing the DNA adduct N1-(2-. Bulky DNA adducts, 4-aminobiphenyl-haemoglobin adducts and diet in the and the levels of biomarkers related to exposure to aromatic compounds is highly relevant. Fibres could reduce the formation of DNA adducts in different manners, Relationship between HMF intake and SMF formation in vivo: An animal and We found increased concentrations of SMF in plasma and DNA SMF-adducts in tissues was observed by MALDI-MS imaging technology due to low sensitivity.

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Indeed, the bulky substituent may improve the stability of (non-native) Hoogsteen pairs. BACKGROUND: Colorectal (CRC) and gastric cancer (GC) are associated with meat intake and tobacco smoke, maybe because of aromatic compounds occurring in tobacco smoking and formed during cooking meat. Activated metabolites of these compounds may bind to DNA forming bulky adducts. Adduct formation is the result of a covalent binding between reactive electrophilic substances and the nucleophilic sites in DNA and proteins.

The results link gene research with the nutritional and environmental approaches to medicine. Early indications are that the burden of DNA adducts may be reduced by nutritional intervention. Mutations in critical genes can result in malignant transformation. Several techniques are available with sufficient sensitivity to detect DNA adducts formed as a consequence of occupational or environmental exposure to carcinogens. Detection and identification of DNA adducts in human DNA can provide important clues to the aetiology of cancer. Molecular studies have revealed that DNA adducts block polymerase replication activity, contributing to the increased DNA damage by reducing the repair activity (Hsu et al. 2005).
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Analysis of DNA adducts formed in vivo can help to improve risk assessment and contribute to better understanding of the mechanisms of chemical carcinogenesis.

For B[a]P and other PAHs, the magnitude of DNA adduct formation depends on the metabolic capacity of the target cells (Boysen and Hecht 2003 ). Our results indicate that TAM-DNA adducts are formed via O -sulfonation, not O -acetylation, of α-hydroxylated TAM and its metabolites. Unfortunately, treatment of TAM increases the incidence of endometrial cancer; this may be due to the genotoxic damage induced by TAM metabolites. Therefore, such DNA damage produced by AA-DNA adducts is one rare example of the direct association of exposure and cancer development (UUC) in humans, confirming that the covalent binding of carcinogens to DNA is causally related to tumourigenesis.
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DNA adducts formed by ethene and - AVHANDLINGAR.SE

The main parts of the thesis are characterisation of DNA adducts formed by the studied epoxides, development of quantitative methods for the analysis of epoxideinduced adducts and analysis of such adducts in animal and human tissue … 17 hours ago Due to its low toxicity, DMPO can be used in cells at high enough concentrations to out-compete the normal reactions of DNA radicals, thus ensuring a high yield of DNA nitrone adducts. Because A structurally-related adduct of sterigmatocystin formed a similar intercalated structure (47). Unlike most DNA adducts, the AFB 1 N7-dG adducts thermodynamically stabilized the DNA duplex, as evidenced by increases in duplex melting temperatures (T m studies), as monitored either by … DMBA-DNA adducts formed in mouse epidermis by enantiomers of tram-3,4-dihydrodiol via their DMBA-3,Cdihydrodiol 1,2-epoxides have been reported (8). Three stable DNA adducts arising from reaction of bay-region diolepoxides of DMBA with dA and dG have been previously identified (9,101.

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DNA adducts formed by ethene and - AVHANDLINGAR.SE

The These covalent adducts are formed by linking the 3, 4 or 4', 5’ edge of psoralen to the 5, 6 double bond of thymine. Psoralens can form two types of monoadducts and one diadduct (an interstrand crosslink) with thymine. These adducts result in local distortions to DNA at the site of intercalation. 2009-07-13 · Nickel DNA adducts were found in some non-smokers and nickel is a known carcinogen. Lindane DNA adducts are identified for the first time. The results link gene research with the nutritional and environmental approaches to medicine.

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Hence, the reference to large bulky adducts and small DNA adducts. Small DNA adducts can occur both from chemical exposure and from normal metabolic processes. Investigating DNA adduct formation by flavor chemicals and tobacco byproducts in electronic nicotine delivery system (ENDS) using in silico approaches Investigating DNA adduct formation by flavor chemicals and tobacco byproducts in electronic nicotine delivery system (ENDS) using in silico approaches M 1 G (pyrimido- [1,2- a ]purin-10 (3H)-one) adducts are formed in the reaction of DNA with MDA (malondialdehyde), the most abundant carbonyl product of lipid peroxidation [73].

We have isolated and purified this adduct formed under oxido-reductive (Fenton) conditions in Tris buffer. We show by homo- and heteronuclear NMR spectroscopy that the covalent Adriamycin-DNA adduct is structurally We are involved in a systematic search for novel mutagenic lesions formed by oxidation. By identifying the DNA adducts of environmental carcinogens and drugs that are deleterious to humans, we can implement intervention strategies that minimize risk to humans who are exposed to these agents. pyridyloxobutyl DNA adducts, a critical step in its mechanism of carcinogenesis. In addition to DNA nucleobase adducts, DNA phosphate adducts can be formed by pyridyloxobutyla-tion of the oxygen atoms of the internucleotidic phosphodiester linkages.