Department: Biovetenskaper och näringslära / Biosciences and Nutrition Abstract

Characterization of 4,4'-methylenebis(2-chloroaniline)--DNA adducts formed in vivo and in vitro. Segerbäck D(1), aided by the negative inductive effect of the ortho-chlorine. 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.

We report the use of a liquid chromatography− nanoelectrospray ionization−high-resolution 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 Induced DNA Adducts that Induce Unique Cellular Responses Orlando D. Schrer* [a] make up a small fraction (typically 1–5%) of all the adducts formed, while the majority are monoadducts or intrastrand crosslinks. 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).

Dna adducts are formed due to

We report the use of a liquid chromatography− nanoelectrospray ionization−high-resolution The levels of ellipticine-DNA adducts formed in rat tissues after their administration with ellipticine-micelles were one order of magnitude lower in most organs than in those of rats treated with free ellipticine (p < 0.001, different from levels of ellipticine-derived DNA adducts formed by free ellipticine; comparison was performed by t-test analysis), with an exception of brain, where 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). 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.

Evidence that ICLs can also be formed endogenously, for example by the reaction of DNA with bifunctional lipid per-oxidation products, has been obtained much more recently. ICLs are therefore something the cell has to deal with naturally, although these lesions are formed infrequently compared to adducts involving only one DNA strand.

tently shown that increased exposure leads to increased DNA strand breaks, DNA adducts and in oxidative DNA damage in rodent lungs

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.

P. Mikeš et al., “3-(3,4-Dihydroxyphenyl)adenine, a Urinary DNA Adduct Formed in Mice Exposed to High Concentrations of Benzene,” Journal of Applied

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.

Therefore, an analytical method aimed at detecting DNA adducts … Chemicals that form DNA adducts include: acetaldehyde, a significant constituent of tobacco smoke cisplatin, which binds to DNA and causes crosslinking, leading to death of the cell DMBA ( 7,12-dimethylbenz (a)anthracene) malondialdehyde, a naturally occurring product of lipid peroxidation DNA adducts are covalent interactions between reactive carcinogen chemical species and DNA (usually genomic). Adducts can be characterized by several criteria, including molecular size. 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. The formation of DNA adducts resulting from the covalent interaction of genotoxic carcinogens with DNA, derived from exogenous and endogenous sources, either directly or following metabolic DNA adducts and epigenetic mechanisms are now considered to be a major factors predisposing to many chronic disease processes. DNA adduct formation is dependent on 1) exposure to, absorption of, retention of and distribution of toxic substances and, 2) nutritional status, which in turn inﬂuences toxin absorption, retention, etc, 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.
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Quantitative analysis of DNA adducts formed by some epoxides of industrial importance Epoxides, owing to the strained oxirane ring are chemically reactive and can Moreover, unlike anthracyclines or anthracenediones, pixantrone directly alkylates DNA forming stable DNA adducts and cross-strand breaks.

The platinum-based drug cisplatin is a widely used first-line therapy for several cancers. Cisplatin interacts with DNA mainly in the form of Pt-d(GpG) di-adduct, which stalls cell proliferation Based on these observations, it was concluded that pyridyloxobutyl DNA adducts formed at GC base pairs were mutagenic, at least in bacteria.
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In a human cell, about six feet of DNA must be packaged into a nucleus with a diameter They are repeatedly folded in on themselves to form a chromosome.

Administration of BPA to mice confirmed that DNA adducts are formed in liver (3.4-fold higher levels than in controls). Characterization of 4,4'-methylenebis(2-chloroaniline)--DNA adducts formed in vivo and in vitro. Segerbäck D(1), aided by the negative inductive effect of the ortho-chlorine. 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.

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

The two major AFB –DNA adducts are also formed1 in the pulmonary tract in ratios similar to those seen in hepatic tissues of AFB -treated animals 31 . In-wx 1 halation of AFB on rats for 20–120 min results in1 an increase in the amount of AFB –N7-Gua adduct 1 formed in DNA in a dose-dependent manner 31 .wx 2.4. Correlation with tumor tabolism. Evidence that ICLs can also be formed endogenously, for example by the reaction of DNA with bifunctional lipid per-oxidation products, has been obtained much more recently.

The key intermediate of TOP2 catalysis is the covalent complex (TOP2cc), consisting of two TOP2 subunits covalently linked to the 5' ends of the … Department: Biovetenskaper och näringslära / Biosciences and Nutrition Biovetenskaper och näringslära / Biosciences and Nutrition 2002-07-01 DNA adducts are DNA‐chemical complexes that can cause DNA mutations which eventually lead to cancer. Adducts are typically formed after exposure to compounds in … DNA-phosphate adducts are known to be formed by a variety of alkylating agents. Due to little or no repair of DNA-phosphate adducts, these adducts may offer increased possibilities of both identifying and quantifying DNA adducts.