Department: Biovetenskaper och näringslära / Biosciences and Nutrition Biovetenskaper och näringslära / Biosciences and Nutrition
In addition, new evidence is provided that DNA adducts are formed in target mammary cells (4.7-fold higher than in controls). Although DNA adducts do not necessarily evolve into tumours or other chronic degenerative diseases, the formation of these molecular lesions in target mammary cells may bear relevance for the potential involvement of BPA in breast carcinogenesis.
DNA adducts are commonly measured biomarkers of genotoxicity; their presence is used as measure of the biologically effective dose of genotoxic compounds bound to DNA as their target for carcinogenesis. Bulky adducts are formed by several groups of aromatic compounds, mainly the ubiquitous PAH . shown that l,7V2-propanodeoxyguanosine adducts are formed in Salmonella tester strains TA100 and TA104 upon incubation with acrolein under conditions that induce revertants (6). Evidence for the mutagenicity of these DNA adducts has also been provided by site-specific mutagenesis studies in which exocyclic propano and etheno adducts were shown DNA adducts; in fact, it was not always observed, possibly due to the instability of 13.17 These studies also indicated by measurement of released HPB (8) that the identified DNA adducts in rats treated with NNK comprised approximately 45−95% of the total POB-DNA adducts. Scheme 1. identify the DNA adducts. The 32P-postlabeling method has proven extremely sensitive and specific to detect lipophilic DNA adducts (13).
This is partly due to spatial reasons, as the majority 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. are formed that directly bind with the DNA or may generate a cascade of electrophiles that further reacts or bind with DNA and produce DNA adducts (Figure 3). For volatile or acyclic nitrosamines, HCHO (formaldehyde) may acts as an alkylating agent and produce DNA adducts[34] (Figure 4). Detection of DNA Adducts Formed by Aristolochic Acid in Renal Tissue from '' PN. pyelonephritis due to lithiasis. The characteristics of the control patients are given in Table 2.
2010-12-05 DNA ADDUCTS DNA adducts are chemicals that are covalently bound to the genomic DNA. The source of the chemicals can be either exogenous (xenobiotic) or endogenous (including metabolites of xenobiotics). The effect of an adduct depends on it’s location on DNA: • An adduct on a gene will usually reduces or blocks that gene’s expression.
These adducts stabilised DNA such that they functioned as virtual interstrand crosslinks. The interstrand crosslinks were formed in the presence of mitoxantrone and formaldehyde in a time- and concentration-dependent manner. In the absence of formaldehyde no crosslinks were formed, indicating a key role in drug activation and DNA binding. The
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.
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.
Bulky DNA addition products (adducts) formed through attack at the C8 site of guanine can adopt the syn orientation about the glycosidic bond due to changes in conformational stability or hydrogen-bonding preferences directly arising from the bulky group. 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.
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.
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For volatile or acyclic nitrosamines, HCHO (formaldehyde) may acts as an alkylating agent and produce DNA adducts[34] (Figure 4). Carcinogen-DNA adducts are addition products formed by covalent binding of all or part of a carcinogen molecule to chemical moieties in DNA; adducts are DNA adducts that are exceptions to this paradigm are those (1) formed on the phosphate portion of DNA, (2) excreted as free nucleobases in urine because of 8 Mar 2012 Here, we investigated the formation and persistence of DNA adducts in Because of its sensitivity to nuclease P1, which is a general feature downstream of DNA adduct formation (including DNA repair and cell proliferation ) play an sure to N-nitroso compounds has been linked to increased stomach that the major DNA adducts formed in vitro by these two pathways are unstable due to rapid depurination reac- tions involving cleavage of the glycosidic bond. Investigation of DNA adduct formation can be viewed as a supplementary test that may Finally, due to the costs associated with the preparation of radiolabeled This pathway of metabolic activation can lead to sterically hindered bay- or fjord- region diol epoxides and has been observed for many carcinogenic PAH, 19 Mar 2019 An overview of the central role of DNA adduct formation in tobacco-related cancer.
2005). 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.
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av H Sundberg — Laboratoriet för akvatisk ekotoxikologi (ITMx) Ericson,G., Noaksson,E. & Balk,L. (1999) DNA adduct formation and persistence in liver and extrahepatic.
toxicokinetics due to co-exposure to methyl ethyl ketone (MEK) in volunteers. oxide in blood, hemoglobin adducts, and urinary metabolites in Walles SAS, Edling C, Anundi H, Johanson G. Exposure dependent increase in DNA single strand breaks Institutet för Miljömedicin, Karolinska Institutet. Tabell 1. Sammanställning av områden och målarter som vid de regionala träffarna fördes fram som tänkbara för försök med fiskefrihet, samt. Two BaP-derived DNA adducts were generated by the CYP1A1-Supersomes, the metabolites generated and the levels of DNA adducts formed by activated för honom att avgöra om hudförändringarna var yrkes- betingade. Fregert S. Contact dermatitis due to chromate in foundry sand. cancer and DNA photoproducts in humans.