Category: 55662-66-3

On November 15, 2003, Barbin, Alain; Wang, Rong; O’Connor, Peter J.; Elder, Rhoderick H. published an article.Related Products of 55662-66-3 The title of the article was Increased Formation and Persistence of 1,N6-Ethenoadenine in DNA Is Not Associated with Higher Susceptibility to Carcinogenesis in Alkylpurine- DNA-N-Glycosylase Knockout Mice Treated with Vinyl Carbamate. And the article contained the following:

Ethenobases are promutagenic DNA adducts formed by some environmental carcinogens and products of endogenous lipid peroxidation Mutation spectra in tumors induced in mice by urethane or its metabolite vinyl carbamate (Vcar) are compatible with 1,N6-ethenoadenine (εA) being an initiating lesion in the development of these tumors. As alkylpurine-DNA-N-glycosylase (APNG) releases εA from DNA in vitro, wild-type and APNG-/- C57Bl/6J mice were treated with Vcar and levels of εA and 3,N4-ethenocytosine (εC), which is not a substrate of APNG, were analyzed in liver and lung DNA. At 6 h after the last dose, levels of εA were 1.6-fold higher in DNA from APNG-/- mice and subsequently persisted at higher levels for longer than in DNA from wild-type animals, confirming that εA is released by APNG in vivo. In contrast, ∼14-fold lower levels of εC were induced by Vcar, and the kinetics of formation and persistence of εC was similar in the two mouse strains. The carcinogenicity of Vcar was compared in APNG-/- and wild-type suckling mice given a single dose of Vcar (30 or 150 nmol/g). After 1 yr, only mice in the high-dose group developed hepatocellular carcinoma; however, the incidence was not higher in APNG-/- mice. Although higher levels and increased persistence of εA was observed in hepatic DNA from APNG-/- mice at 150 nmol/g Vcar, apoptosis and cell proliferation levels were similar in both strains of mice. This may explain why differences in εA formation/persistence observed here did not result in higher susceptibility of APNG-/- mice to hepatocarcinogenesis. The experimental process involved the reaction of Imidazo[1,2-c]pyrimidin-5(6H)-one(cas: 55662-66-3).Related Products of 55662-66-3

The Article related to ethenoadenine genetic susceptibility vinyl carbamate, alkylpurine n glycosylase gene vinyl carbamate carcinogenesis, Toxicology: Carcinogens, Mutagens, and Teratogens and other aspects.Related Products of 55662-66-3

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Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

On June 30, 1985, Barbin, Alain; Laib, Reinhold J.; Bartsch, Helmut published an article.COA of Formula: C6H5N3O The title of the article was Lack of miscoding properties of 7-(2-oxoethyl)guanine, the major vinyl chloride-DNA adduct. And the article contained the following:

Chloroethylene oxide  [7763-77-1], an ultimate carcinogenic metabolite of vinyl chloride, was reacted with poly(deoxyguanylate-deoxycytidylate) [36786-90-0]; the nucleic acid base adducts, 7-(2-oxoethyl)guanine  [73100-87-5] and 3,N4-ethenocytosine  [55662-66-3], were analyzed by reversed-phase HPLC. Chloroethylene oxide-modified poly(deoxyguanylate-deoxycytidylate) was assayed as template in a replication fidelity assay with Escherichia coli DNA polymerase I  [9012-90-2], and the newly synthesized product was subjected to nearest-neighbor anal. Misincorporation rates of dAMP  [653-63-4] and TMP  [365-07-1] were increased with the level of template modification. About 80% of the mispairing events were located opposite minor cytosine lesions. 7-(2-Oxoethyl)guanine, the major adduct identified (>98% of the adducts), did not miscode for either thymine or adenine, failing to support an earlier hypothesis that the cyclic hemiacetal form, O6,7-(1′-hydroxyethano)guanine, could, by anal. with O6-methyl- and O6-ethylguanine, simulate adenine. Thus, direct miscoding of 7-(2-oxoethyl)guanine may contribute only slightly to the induction of mutations by chloroethylene oxide. The experimental process involved the reaction of Imidazo[1,2-c]pyrimidin-5(6H)-one(cas: 55662-66-3).COA of Formula: C6H5N3O

The Article related to oxyethylguanine chloroethylene oxide dna coding, ethenocytosine nucleic acid coding chloroethylene oxide, Toxicology: Carcinogens, Mutagens, and Teratogens and other aspects.COA of Formula: C6H5N3O

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Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Barbin, A. published an article in 1999, the title of the article was Role of etheno DNA adducts in carcinogenesis induced by vinyl chloride in rats.Safety of Imidazo[1,2-c]pyrimidin-5(6H)-one And the article contains the following content:

A review and discussion with many references Vinyl chloride, a hepatocarcinogen in humans and rodents, can form promutagenic ethano bases in DNA after metabolic activation. The formation of 1,N6-ethenoadenine (εA) and 3,N4-ethenocytosine (εC) was measured in adult Sprague-Dawley rats by immunoaffinity purification and 32P-post-labeling. A highly variable background was found in all tissues from untreated animals: the mean molar ratios of εA:A and εC:C in DNA ranged from 0.043 × 10-8 to 31.2 × 10-8 and from 0.062 × 10-8 to 20.4 × 10-8, resp. After exposure to 500 ppm vinyl chloride by inhalation (4 h/day, 5 days/wk for 8 wk), increased levels of εA were found in the liver, lung, circulating lymphocytes and testis, the mean (± SD) of induced levels (treated-control values) being (4.1±1.5) × 10-8 for these tissues. No increase in the εA:A ratio was observed in kidney, brain or spleen. The levels of εC increased in all the tissues examined except the brain. The mean value of the induced εC:C ratios was (7.8±1.2) × 10-8 for the liver, kidney, lymphocytes and spleen, and these ratios were higher in the lung (28×10-8) and testis (19×10-8). The results suggest a variable repair capacity for εA or εC in different tissues. The results are discussed in relation to published studies on the accumulation and persistence of etheno bases in the liver during and after exposure to vinyl chloride and on mutation spectra in the ras and p53 genes in liver tumors induced by vinyl chloride. In addition, we show that the linear relationship established for monofunctional alkylating agents between their carcinogenic potency in rodents and their covalent binding index for promutagenic bases in hepatic DNA holds for vinyl chloride. It is concluded that etheno bases are critical lesions in hepatocarcinogenesis induced by vinyl chloride. For a better understanding of the mechanism of action of this compound, further work is needed on the role of DNA repair pathways and of endogenous lipid peroxidation products in the formation and persistence of etheno bases in vivo. The experimental process involved the reaction of Imidazo[1,2-c]pyrimidin-5(6H)-one(cas: 55662-66-3).Safety of Imidazo[1,2-c]pyrimidin-5(6H)-one

The Article related to etheno dna adduct carcinogenesis vinyl chloride, review etheno dna adduct carcinogenesis vinyl chloride, Toxicology: Carcinogens, Mutagens, and Teratogens and other aspects.Safety of Imidazo[1,2-c]pyrimidin-5(6H)-one

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Imidazole | C3H4N2 – PubChem

Barbin, Alain; Bartsch, Helmut; Lecomte, Philippe; Radman, Miroslav published an article in 1981, the title of the article was On the possible role of the miscoding DNA lesions, 1,N6-ethenoadenine and 3,N4-ethenocytosine, in vinyl chloride-induced mutagenesis and carcinogenesis.Related Products of 55662-66-3 And the article contains the following content:

chloroacetaldehyde  [107-20-0] And chloroethylene oxide (CEO) [7763-77-1], 2 reactive metabolites of vinyl chloride  [75-01-4], were used to introduce increasing amounts of 1,N6-ethenoadenine (εA)(I) [13875-63-3] and 3,N4-ethenocytosine (εC)(II) [55662-66-3] residues in poly(dA) [25191-20-2] and poly(dC) [25609-92-1], resp. The modified polynucleotides were assayed with Escherichia coli DNA polymerase I for their template activity and misincorporation. The miscoding properties observed of εA and εC may explain the mutagenic effects reported for vinyl chloride and its metabolites; these lesions may also represent one of the initial steps in vinyl chloride- or CEO-induced carcinogenesis. The experimental process involved the reaction of Imidazo[1,2-c]pyrimidin-5(6H)-one(cas: 55662-66-3).Related Products of 55662-66-3

The Article related to vinyl chloride mutagenesis dna miscoding, carcinogenesis vinyl chloride ethenoadenine ethenocytosine, Toxicology: Carcinogens, Mutagens, and Teratogens and other aspects.Related Products of 55662-66-3

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Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

On February 3, 2010, Maciejewska, Agnieszka M.; Ruszel, Karol P.; Nieminuszczy, Jadwiga; Lewicka, Joanna; Sokolowska, Beata; Grzesiuk, Elzbieta; Kusmierek, Jaroslaw T. published an article.Related Products of 55662-66-3 The title of the article was Chloroacetaldehyde-induced mutagenesis in Escherichia coli: The role of AlkB protein in repair of 3,N4-ethenocytosine and 3,N4-α-hydroxyethanocytosine. And the article contained the following:

Etheno (ε) adducts are formed in reaction of DNA bases with various environmental carcinogens and endogenously created products of lipid peroxidation Chloroacetaldehyde (CAA), a metabolite of carcinogen vinyl chloride, is routinely used to generate ε-adducts. The authors studied the role of AlkB, along with AlkA and Mug proteins, all engaged in repair of ε-adducts, in CAA-induced mutagenesis. The test system used involved pIF102 and pIF104 plasmids bearing the lactose operon of CC102 or CC104 origin which allowed to monitor Lac+ revertants, the latter arose by GC → AT or GC → TA substitutions, resp., as a result of modification of guanine and cytosine. The plasmids were CAA-damaged in vitro and replicated in Escherichia coli of various genetic backgrounds. To modify the levels of AlkA and AlkB proteins, mutagenesis was studied in E. coli cells induced or not in adaptive response. Formation of εC proceeds via a relatively stable intermediate, 3,N4-α-hydroxyethanocytosine (HEC), which allowed to compare repair of both adducts. The results indicate that all three genes, alkA, alkB and mug, are engaged in alleviation of CAA-induced mutagenesis. The frequency of mutation was higher in AlkA-, AlkB- and Mug-deficient strains in comparison to alkA +, alkB +, and mug + controls. Considering the levels of CAA-induced Lac+ revertants in strains harboring the pIF plasmids and induced or not in adaptive response, the authors conclude that AlkB protein is engaged in the repair of εC and HEC in vivo. Using the modified TTCTT 5-mers as substrates, the authors confirmed in vitro that AlkB protein repairs εC and HEC although far less efficiently than the reference adduct 3-methylcytosine. The pH optimum for repair of HEC and εC is significantly different from that for 3-methylcytosine. The authors propose that the protonated form of adduct interact in active site of AlkB protein. The experimental process involved the reaction of Imidazo[1,2-c]pyrimidin-5(6H)-one(cas: 55662-66-3).Related Products of 55662-66-3

The Article related to chloroacetaldehyde mutagen escherichia alkb ethenocytosine hydroxyethanocytosine repair, Toxicology: Carcinogens, Mutagens, and Teratogens and other aspects.Related Products of 55662-66-3

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Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

On October 26, 1982, Kusmierek, J. T.; Singer, B. published an article.Recommanded Product: 55662-66-3 The title of the article was Chloroacetaldehyde-treated ribo- and deoxyribopolynucleotides. 1. Reaction products. And the article contained the following:

The in vitro reaction of the vinyl chloride metabolite chloracetaldehyde (CAA) [107-20-0] with cytosine and adenine residues in ribo- and deoxyribopolynucleotides leads to the formation of the relatively stable hydrated etheno derivatives 3,N4-(N4-α-hydroxyethano)cytosine (εC.H2O) [66547-58-8] and 1,N6-(N6-α-hydroxyethano)adenine (εA.H2O) [69260-72-6]. Under physiol. conditions, the hydrates are slowly converted to 3,N4-ethenocytosine (εC)(I) [55662-66-3] and 1,N6-ethenoadenine (εA) [13875-63-3]. The half-life at pH 7.25 of εC.H2O in poly(C) is 4.9 h at 50° and of εA.H2O in poly(A) is 1.4 h at 37°. These dehydration rates in polymers are similar to those for hydrates in monomers. The reactivity of adenine and cytosine residues is greatly suppressed in double-stranded polymers. Adenine residues are ∼10 times less reactive in poly(A).poly(U) than adenine in single-stranded polymers. Under similar reaction conditions no reaction of cytosine residues in poly(C).poly(G) was detected. In vinyl chloride exposed cells, where CAA is formed, the cyclic etheno derivatives of adenine and cytosine are likely to occur preferentially in single-stranded regions of nucleic acids, with the hydrate forming a major proportion of the modification. The experimental process involved the reaction of Imidazo[1,2-c]pyrimidin-5(6H)-one(cas: 55662-66-3).Recommanded Product: 55662-66-3

The Article related to chloracetaldehyde reaction nucleic acid, polynucleotide reaction chloracetaldehyde, Toxicology: Carcinogens, Mutagens, and Teratogens and other aspects.Recommanded Product: 55662-66-3

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Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

On April 23, 2004, Gros, Laurent; Maksimenko, Andrei V.; Privezentzev, Cyril V.; Laval, Jacques; Saparbaev, Murat K. published an article.Name: Imidazo[1,2-c]pyrimidin-5(6H)-one The title of the article was Hijacking of the Human Alkyl-N-purine-DNA Glycosylase by 3,N4-Ethenocytosine, a Lipid Peroxidation-induced DNA Adduct. And the article contained the following:

Lipid peroxidation generates aldehydes, which react with DNA bases, forming genotoxic exocyclic etheno(ε)-adducts. E-bases have been implicated in vinyl chloride-induced carcinogenesis, and increased levels of these DNA lesions formed by endogenous processes are found in human degenerative disorders. E-adducts are repaired by the base excision repair pathway. Here, the authors report the efficient biol. hijacking of the human alkyl-N-purine-DNA glycosylase (ANPG) by 3,N4-ethenocytosine (εC) when present in DNA. Unlike the ethenopurines, ANPG does not excise, but binds to εC when present in either double-stranded or single-stranded DNA. The authors developed a direct assay, based on the fluorescence quenching mechanism of mol. beacons, to measure a DNA glycosylase activity. Mol. beacons containing modified residues have been used to demonstrate that the εC·ANPG interaction inhibits excision repair both in reconstituted systems and in cultured human cells. Furthermore, the authors show that the εC·ANPG complex blocks primer extension by the Klenow fragment of DNA polymerase I. These results suggest that εC could be more genotoxic than 1,N6-ethenoadenine (εA) residues in vivo. The proposed model of ANPG-mediated genotoxicity of εC provides a new insight in the mol. basis of lipid peroxidation-induced cell death and genome instability in cancer. The experimental process involved the reaction of Imidazo[1,2-c]pyrimidin-5(6H)-one(cas: 55662-66-3).Name: Imidazo[1,2-c]pyrimidin-5(6H)-one

The Article related to genotoxicity ethenocytosine lipid peroxidation dna adduct human anpg, Toxicology: Carcinogens, Mutagens, and Teratogens and other aspects.Name: Imidazo[1,2-c]pyrimidin-5(6H)-one

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Kowalczyk, Pawel; Ciesla, Jaroslaw M.; Saparbaev, Murat; Laval, Jacques; Tudek, Barbara published an article in 2006, the title of the article was Sequence-specific p53 gene damage by chloroacetaldehyde and its repair kinetics in Escherichia coli.Related Products of 55662-66-3 And the article contains the following content:

Oxidative stress and certain environmental carcinogens, e.g. vinyl chloride and its metabolite chloroacetaldehyde (CAA), introduce promutagenic exocyclic adducts into DNA, among them 1,N6-ethenoadenine (εA), 3,N4-ethenocytosine (εC) and N2,3-ethenoguanine (εG). We studied sequence-specific interaction of the vinyl-chloride metabolite CAA with human p53 gene exons 5-8, using DNA Polymerase Fingerprint Anal. (DPFA), and identified sites of the highest sensitivity. CAA-induced DNA damage was more extensive in p53 regions which revealed secondary structure perturbations, and were localized in regions of mutation hot-spots. These perturbations inhibited DNA synthesis on undamaged template. We also studied the repair kinetics of CAA-induced DNA lesions in E. coli at nucleotide resolution level. A plasmid bearing full length cDNA of human p53 gene was modified in vitro with 360 mM CAA and transformed into E. coli DH5α strain, in which the adaptive response system had been induced by MMS treatment before the cells were made competent. Following transformation, plasmids were re-isolated from transformed cultures 35, 40, 50 min and 1-24 h after transformation, and further subjected to LM-PCR, using ANPG, MUG and Fpg glycosylases to identify the sites of DNA damage. In adaptive response-induced E. coli cells the majority of DNA lesions recognized by ANPG glycosylase were removed from plasmid DNA within 35 min, while MUG glycosylase excised base modifications only within 50 min, both in a sequence-dependent manner. In non-adapted cells resolution of plasmid topol. forms was perturbed, suggesting inhibition of one or more bacterial topoisomerases by unrepaired ε-adducts. We also observed delayed consequences of DNA modification with CAA, manifesting as secondary DNA breaks, which appeared 3 h after transformation of damaged DNA into E. coli, and were repaired after 24 h. The experimental process involved the reaction of Imidazo[1,2-c]pyrimidin-5(6H)-one(cas: 55662-66-3).Related Products of 55662-66-3

The Article related to p53 gene dna damage repair kinetics chloroacetaldehyde escherichia, Toxicology: Carcinogens, Mutagens, and Teratogens and other aspects.Related Products of 55662-66-3

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Imidazole | C3H4N2 – PubChem

On January 16, 1994, Simha, Devendranath; Yadav, Deepmala; Rzepka, Robert W.; Palejwala, Vaseem A.; Humayun, M. Zafri published an article.Computed Properties of 55662-66-3 The title of the article was Base incorporation and extension at a site-specific ethenocytosine by Escherichia coli DNA polymerase I Klenow fragment. And the article contained the following:

Ethenocytosine (εC) is a highly mutagenic exocyclic DNA lesion induced by carcinogens vinyl chloride and urethane. The authors have examined base incorporation and extension at a site-specific εC residue by a quant. gel electrophoretic assay using an exonuclease-deficient version of Escherichia coli DNA polymerase I (Klenow fragment) as the model enzyme. The data show that the KM for incorporation of adenine or thymine opposite εC by is about 5 orders of magnitude higher than that for the incorporation of guanine opposite normal cytosine. The KM for base extension past εC:A and εC:T pairs is 1-2 orders of magnitude higher than that observed for a C:G pair. Although adenine misinsertion is favored over that of thymine, base extension occurs more readily when the base incorporated opposite εC is thymine. The experimental process involved the reaction of Imidazo[1,2-c]pyrimidin-5(6H)-one(cas: 55662-66-3).Computed Properties of 55662-66-3

The Article related to ethenocytosine base incorporation extension escherichia polymerase, Toxicology: Carcinogens, Mutagens, and Teratogens and other aspects.Computed Properties of 55662-66-3

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

On March 7, 2003, Abu, Mika; Waters, Timothy R. published an article.COA of Formula: C6H5N3O The title of the article was The Main Role of Human Thymine-DNA Glycosylase Is Removal of Thymine Produced by Deamination of 5-Methylcytosine and Not Removal of Ethenocytosine. And the article contained the following:

Metabolites of vinyl chloride react with cytosine in DNA to form 3,N4-ethenocytosine. Recent studies suggest that ethenocytosine is repaired by the base excision repair pathway with the ethenobase being removed by thymine-DNA glycosylase. Here single turnover kinetics have been used to compare the excision of ethenocytosine by thymine-DNA glycosylase with the excision of thymine. The effect of flanking DNA sequence on the excision of ethenocytosine was also investigated. The 34-bp duplexes studied here fall into three categories. Ethenocytosine base-paired with guanine within a CpG site (i.e. CpG·εC-DNA) was by far the best substrate having a specificity constant (k2/Kd) of 25.1×106 M-1 s-1. The next best substrates were DNA duplexes containing TpG·εC, GpG·εC, and CpG·T. These had specificity constants 45-130 times smaller than CpG·εC-DNA. The worst substrates were DNA duplexes containing ApG·εC and TpG·T, which had specificity constants, resp., 1,600 and 7,400 times lower than CpG·εC-DNA. DNA containing ethenocytosine was bound much more tightly than DNA containing a G·T mismatch. This is probably because thymine-DNA glycosylase can flip out ethenocytosine from a G·εC base pair more easily than it can flip out thymine from a G·T mismatch. Because thymine-DNA glycosylase has a larger specificity constant for the removal of ethenocytosine, it has been suggested its primary purpose is to deal with ethenocytosine. However, these results showing that thymine-DNA glycosylase has a strong sequence preference for CpG sites in the excision of both thymine and ethenocytosine suggest that the main role of thymine-DNA glycosylase in vivo is the removal of thymine produced by deamination of 5-methylcytosine at CpG sites. The experimental process involved the reaction of Imidazo[1,2-c]pyrimidin-5(6H)-one(cas: 55662-66-3).COA of Formula: C6H5N3O

The Article related to thymine dna glycosylase deamination methylcytosine ethenocytosine, Toxicology: Carcinogens, Mutagens, and Teratogens and other aspects.COA of Formula: C6H5N3O

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Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem