Genomes and Genes
Summary: Covalent adducts between chemical mutagens and DNA. Such couplings activate DNA repair processes and, unless repaired prior to DNA replication, may lead to nucleotide substitutions, deletions, and chromosome rearrangements. (Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)
Publications390 found, 100 shown here
- Molecular mechanisms of mammalian global genome nucleotide excision repairLudovic C J Gillet
Institute for Molecular Cancer Research, University of Zurich, Switzerland
Chem Rev 106:253-76. 2006
- Mechanisms of resistance to cisplatinM Kartalou
Division of Bioengineering and Environmental Health and Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
Mutat Res 478:23-43. 2001..An improved understanding of the mechanisms of resistance operative in vivo has identified targets for intervention and may increase the utility of cisplatin for the treatment of cancer...
- XRCC1, XRCC3, XPD gene polymorphisms, smoking and (32)P-DNA adducts in a sample of healthy subjectsG Matullo
Dipartimento di Genetica, Biologia e Biochimica, Universita di Torino, 10126, Torino, ISI Foundation, Institute for Scientific Interchange, Villa Gualino, 10133, Torino, Italy
Carcinogenesis 22:1437-45. 2001..These data show that all the analysed polymorphisms could result in deficient DNA repair and suggest a need for further investigation into the possible interactions between these polymorphisms, smoking and other risk factors...
- Doxorubicin-DNA adducts induce a non-topoisomerase II-mediated form of cell deathLonnie P Swift
Department of Biochemistry, La Trobe University, Victoria, Australia
Cancer Res 66:4863-71. 2006..Here, we show that doxorubicin-DNA adducts (formed by the coadministration of doxorubicin with non-toxic doses of formaldehyde-releasing prodrugs) induce ..
- Aristolochic acid nephropathy: a worldwide problemFrédéric D Debelle
Department of Nephrology, Dialysis and Renal Transplantation, Erasme Hospital, Brussels, Belgium
Kidney Int 74:158-69. 2008..Finally, despite the Food and Drug Administration's warnings concerning the safety of botanical remedies containing AA, these herbs are still sold via the Internet...
- Metabolism and biomarkers of heterocyclic aromatic amines in molecular epidemiology studies: lessons learned from aromatic aminesRobert J Turesky
Division of Environmental Health Sciences, Wadsworth Center, Albany, New York 12201, United States
Chem Res Toxicol 24:1169-214. 2011..Lastly, the analytical approaches that have been successfully employed to biomonitor aromatic amines and HAAs, and emerging biomarkers of HAAs that may be implemented in molecular epidemiology studies are discussed...
- Prenatal exposure to polycyclic aromatic hydrocarbons, benzo[a]pyrene-DNA adducts, and genomic DNA methylation in cord bloodJulie B Herbstman
Department of Environmental Health Sciences, Columbia University Mailman School of Public Health, New York, New York 10032, USA
Environ Health Perspect 120:733-8. 2012..These PAH-DNA adducts are established markers of cancer risk...
- Tobacco smoke carcinogens, DNA damage and p53 mutations in smoking-associated cancersGerd P Pfeifer
Division of Biology, Beckman Research Institute of the City of Hope, Duarte, California, CA 91010, USA
Oncogene 21:7435-51. 2002..The available data suggest that p53 mutations in lung cancers can be attributed to direct DNA damage from cigarette smoke carcinogens rather than to selection of pre-existing endogenous mutations...
- Probing for DNA damage with β-hairpins: similarities in incision efficiencies of bulky DNA adducts by prokaryotic and human nucleotide excision repair systems in vitroYang Liu
Chemistry Department, New York University, New York, NY 10003, USA
DNA Repair (Amst) 10:684-96. 2011..These observations suggest that, in addition to recognition involving the initial modified duplexes, downstream events involving UvrC can also play a role in distinguishing and processing different lesions in prokaryotic NER...
- AHR- and DNA-damage-mediated gene expression responses induced by benzo(a)pyrene in human cell linesSarah L Hockley
Section of Molecular Carcinogenesis, The Institute of Cancer Research, Surrey, UK
Chem Res Toxicol 20:1797-810. 2007..Promoter analysis identified candidate genes for direct transcriptional regulation by either AHR or p53. These analyses have further dissected and characterized the complex cellular response to BaP...
- XRCC1 polymorphisms: effects on aflatoxin B1-DNA adducts and glycophorin A variant frequencyR M Lunn
Laboratory of Computational Biology and Risk Assessment, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA
Cancer Res 59:2557-61. 1999..AFB1-DNA adducts were measured by ELISA, and erythrocyte GPA variant frequency (NN and NO) was assessed in MN heterozygotes with ..
- Oxidative damage to DNA: formation, measurement and biochemical featuresJean Cadet
Laboratoire Lesions des Acides Nucleiques, SCIB DRFMC and FRE 2600, CEA Grenoble, F 38054 Grenoble Cedex 9, France
Mutat Res 531:5-23. 2003..For this purpose modified oligonucleotides in which cyclopurine, and cyclopyrimidine nucleosides were site-specifically inserted were synthesized...
- Lipid peroxidation-DNA damage by malondialdehydeL J Marnett
A B Hancock Jr Memorial Laboratory for Cancer Research Center in Molecular Toxicology, Vanderbilt Cancer Center, Department of Biochemistry, Vanderbilt University School of Medicine, Nashville TN 37232, USA
Mutat Res 424:83-95. 1999..High throughput methods for its detection and quantitation will be extremely useful for screening large populations...
- Importance of chromium-DNA adducts in mutagenicity and toxicity of chromium(VI)Anatoly Zhitkovich
Department of Pathology and Laboratory Medicine, Brown University, Box G E507, Providence, Rhode Island 02912, USA
Chem Res Toxicol 18:3-11. 2005
- Polycyclic aromatic hydrocarbons-aromatic DNA adducts in cord blood and behavior scores in New York city childrenFrederica P Perera
Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, New York 10032, USA
Environ Health Perspect 119:1176-81. 2011Airborne polycyclic aromatic hydrocarbons (PAH) are widespread urban pollutants that can bind to DNA to form PAH-DNA adducts. Prenatal PAH exposure measured by personal monitoring has been linked to cognitive deficits in childhood in a ..
- Upregulation of clusterin in prostate and DNA damage in spermatozoa from bisphenol A-treated rats and formation of DNA adducts in cultured human prostatic cellsSilvio De Flora
Department of Health Sciences, University of Genoa, Genoa, Italy
Toxicol Sci 122:45-51. 2011..We previously demonstrated that administration of BPA to female mice results in the formation of DNA adducts and proteome alterations in the mammary tissue...
- Mirror image stereoisomers of the major benzo[a]pyrene N2-dG adduct are bypassed by different lesion-bypass DNA polymerases in E. coliKwang Young Seo
Biology Department, Boston University, 5 Cummington Street, Boston, MA 02215, USA
DNA Repair (Amst) 5:515-22. 2006....
- In vitro genotoxicity of PAH mixtures and organic extract from urban air particles part II: human cell linesO Sevastyanova
Laboratory of Genetic Ecotoxicology, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Videnska 1083, 142 20 Prague 4, Czech Republic
Mutat Res 620:123-34. 2007..b>DNA adducts were analyzed by (32)P-postlabeling...
- Lipid peroxidation-induced etheno-DNA adducts in the liver of patients with the genetic metal storage disorders Wilson's disease and primary hemochromatosisJ Nair
Division of Toxicology and Cancer Risk Factors, Deutsches Krebsforschungszentrum, Heidelberg, Germany
Cancer Epidemiol Biomarkers Prev 7:435-40. 1998..Thus, the etheno adducts are implicated as initiating DNA damage in copper/iron-induced carcinogenesis in humans and should also be explored as biomarkers in disease progression and prevention trials...
- Formation of PAH-DNA adducts after in vivo and vitro exposure of rats and lung cells to different commercial carbon blacksPaul J A Borm
Particle Research, Institut für Umweltmedizinische Forschung IUF at the Heinrich Heine University, Dusseldorf, Germany
Toxicol Appl Pharmacol 205:157-67. 2005The current study was designed to test the possible release and bioavailability of polycyclic aromatic hydrocarbons (PAHs) from a set of commercial carbon blacks (CBs) as well as the ability of these PAHs to form bulky DNA adducts.
- Human DNA polymerase kappa encircles DNA: implications for mismatch extension and lesion bypassSamer Lone
Department of Structural and Chemical Biology, Mount Sinai School of Medicine, Box 1677, 1425 Madison Avenue, New York, NY 10029, USA
Mol Cell 25:601-14. 2007....
- A single amino acid governs enhanced activity of DinB DNA polymerases on damaged templatesDaniel F Jarosz
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
Nature 439:225-8. 2006....
- Metabolic activation of polycyclic and heterocyclic aromatic hydrocarbons and DNA damage: a reviewWeiling Xue
Department of Environmental Health, University of Cincinnati Medical Center, 3223 Eden Avenue, Cincinnati, OH 45267 0056, USA
Toxicol Appl Pharmacol 206:73-93. 2005..The review emphasizes the chemical/biochemical reactions involved in the metabolic processes and the chemical structures of metabolites and DNA adducts.
- DNA repair gene polymorphisms, bulky DNA adducts in white blood cells and bladder cancer in a case-control studyG Matullo
Dipartimento di Genetica, Biologia e Biochimica, Universita di Torino, Turin, Italy
Int J Cancer 92:562-7. 2001..Results were correlated with DNA damage measured as (32)P-post-labeling bulky DNA adducts in white blood cells from peripheral blood...
- Polkappa protects mammalian cells against the lethal and mutagenic effects of benzo[a]pyreneTomoo Ogi
Laboratories of Gene Information Analysis and Signal Transduction, Institute for Virus Research, Kyoto University, Shogoin Kawara cho 53, Sakyo ku, Japan
Proc Natl Acad Sci U S A 99:15548-53. 2002..Thus, our results indicate that Polkappa plays an important role in suppressing mutations at DNA lesions generated by B[a]P...
- Repair of O(6)-alkylguanine by alkyltransferasesA E Pegg
Departments of Cellular and Molecular Physiology and Pharmacology, Milton S Hershey Medical Center, Pennsylvania State University College of Medicine, P O Box 850, 500 University Drive, Hershey, PA, USA
Mutat Res 462:83-100. 2000..b>DNA adducts at the O(6)-position of guanine are a major factor in the carcinogenic, mutagenic, apoptopic and clastogenic ..
- DNA adducts from acetaldehyde: implications for alcohol-related carcinogenesisPhilip J Brooks
Section on Molecular Neurobiology, Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 5625 Fishers Lane, Room 3S32, MSC 9412, Bethesda, MD 20892 9412, USA
Alcohol 35:187-93. 2005..Inherited variation in the genes encoding the proteins involved in the repair of PdG and its secondary adducts may contribute to susceptibility to alcoholic beverage-related carcinogenesis...
- Polymorphisms in nucleotide excision repair genes, polycyclic aromatic hydrocarbon-DNA adducts, and breast cancer riskKatherine D Crew
Department of Epidemiology, Mailman School of Public Health, Columbia University, 161 Fort Washington Avenue, New York, NY 10032, USA
Cancer Epidemiol Biomarkers Prev 16:2033-41. 2007Genes involved in the nucleotide excision repair (NER) pathway, which removes bulky DNA adducts, are potential low-penetrance cancer susceptibility genes...
- Unusual sequence effects on nucleotide excision repair of arylamine lesions: DNA bending/distortion as a primary recognition factorVipin Jain
Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, RI 02881, USA
Nucleic Acids Res 41:869-80. 2013..This work represents a novel 3'-next flanking sequence effect as a unique NER factor for bulky arylamine lesions in E. coli...
- Exocyclic carbons adjacent to the N6 of adenine are targets for oxidation by the Escherichia coli adaptive response protein AlkBDeyu Li
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
J Am Chem Soc 134:8896-901. 2012..The observation that AlkB can demethylate m6A in vitro suggests a role for AlkB in regulation of important cellular functions in vivo...
- Hepatic aflatoxin B1-DNA adducts and TP53 mutations in patients with hepatocellular carcinoma despite low exposure to aflatoxin B1 in southern JapanKen Shirabe
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
Liver Int 31:1366-72. 2011..Mutations in codon 249, exon 7 are a hallmark of AFB1 exposure. Therefore, to clarify the role of AFB1 in hepatocarcinogenesis, we examined AFB1-DNA in liver tissue and sequenced TP53 in Japanese patients with HCC...
- Formation of acetaldehyde-derived DNA adducts due to alcohol exposureHsu Sheng Yu
Department of Environmental Health, University of Occupational and Environmental Health, Kitakyushu 807 8555, Japan
Chem Biol Interact 188:367-75. 2010..Moreover, they support that chronic alcohol consumption contributes to formation of various DNA adducts. Although some DNA adducts formation is demonstrated to be an initiation step of carcinogenesis, it is still ..
- Genotoxic potential of Polycyclic Aromatic Hydrocarbons-coated onto airborne Particulate Matter (PM 2.5) in human lung epithelial A549 cellsSylvain Billet
LCE EA 2598, Toxicologie Industrielle et Environnementale, Universite du Littoral Cote d Opale, Maison de la Recherche en Environnement Industriel de Dunkerque 2, 189A, Avenue Maurice Schumann, 59140 Dunkerque, France
Cancer Lett 270:144-55. 2008..of Polycyclic Aromatic Hydrocarbons (PAH)-coated onto air pollution PM, and, thereafter, the formation of PAH-DNA adducts in a human lung epithelial cell model (A549 cell line). Cells were exposed to Dunkerque city's PM(2...
- Resveratrol, a natural aryl hydrocarbon receptor antagonist, protects lung from DNA damage and apoptosis caused by benzo[a]pyreneAriel Revel
Division of Reproductive Sciences, Department of Obstetrics and Gynecology, University of Toronto, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario M5G 21X5, Canada
J Appl Toxicol 23:255-61. 2003..in the aetiology of lung cancer through the induction of benzo[a]pyrene diol epoxidation (BPDE) and BPDE-DNA adducts. Because BaP metabolization requires cytochrome P-450 1A1 (CYP1A1) induction through activation of the AhR, we ..
- Efficiency and accuracy of SOS-induced DNA polymerases replicating benzo[a]pyrene-7,8-diol 9,10-epoxide A and G adductsXuan Shen
Department of Biological Sciences and Chemistry, Hedco Molecular Biology Laboratory, University of Southern California, Los Angeles, California 90089 1340, USA
J Biol Chem 277:5265-74. 2002..SOS polymerases are adept at copying a variety of lesions, but the relative contribution of each SOS polymerase to copying damaged DNA appears to be determined by the lesion's identity...
- PAH-DNA adducts in environmentally exposed population in relation to metabolic and DNA repair gene polymorphismsBlanka Binkova
Laboratory of Genetic Ecotoxicology, Institute of Experimental Medicine AS CR and Health Institute of Central Bohemia, Videnska 1083, 14220 Prague, Czech Republic
Mutat Res 620:49-61. 2007..This study investigates relationships between exposure to PAHs, polymorphisms of these genes and DNA adducts in group of occupationally exposed policemen (EXP, N=53, males, aged 22-50 years) working outdoors in the ..
- Alcohol metabolism in human cells causes DNA damage and activates the Fanconi anemia-breast cancer susceptibility (FA-BRCA) DNA damage response networkJessy Abraham
Section on Molecular Neurobiology, Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, NIH, Rockville, Maryland, USA
Alcohol Clin Exp Res 35:2113-20. 2011..We recently reported that exposure of human cells in vitro to acetaldehyde resulted in the activation of the Fanconi anemia-breast cancer susceptibility (FA-BRCA) DNA damage response network...
- The efficiencies of damage recognition and excision correlate with duplex destabilization induced by acetylaminofluorene adducts in human nucleotide excision repairJung Eun Yeo
Department of Chemistry, Stony Brook University, Stony Brook, NY 11794, USA
Chem Res Toxicol 25:2462-8. 2012..Our study is the first systematic analysis correlating these three parameters and supports the idea that initial damage recognition by XPC-RAD23B is a key rate-limiting step in NER...
- Nucleotide misincorporation, 3'-mismatch extension, and responses to abasic sites and DNA adducts by the polymerase component of bacterial DNA ligase DLyudmila Yakovleva
Molecular Biology Program, Sloan Kettering Institute, New York, New York 10021, USA
J Biol Chem 281:25026-40. 2006..Covalent benzo[a]pyrene-dG and benzo[c]phenanthrene-dA adducts in the template strand are durable roadblocks to POL elongation. POL can slowly insert a dNMP opposite the adduct, but is impaired in the subsequent extension step...
- The Raf kinase inhibitor BAY 43-9006 reduces cellular uptake of platinum compounds and cytotoxicity in human colorectal carcinoma cell linesMartina Heim
Department of Internal Medicine and Medical Oncology, West German Cancer Centre, University Medical School of Essen, Essen, Germany
Anticancer Drugs 16:129-36. 2005..spectrometry, BAY significantly reduced cellular uptake of platinum compounds and thereby the generation of DNA adducts. Taken together, co-incubation with BAY results in reduced cellular uptake of platinum compounds and ..
- Synthesis of the C8-deoxyguanosine adduct of the food mutagen IQZ Wang
Department of Chemistry, Vanderbilt University, VU Station B 351822, Nashville, Tennessee 37235-1822, USA
Org Lett 3:565-8. 2001..The key step is a palladium-catalyzed N-arylation of a suitably protected 8-bromo-2'-deoxyguanosine derivative...
- Human biomonitoring: state of the artJurgen Angerer
Institute and Outpatient Clinic of Occupational, Social and Environmental Medicine, University of Erlangen Nuremberg, Schillerstrasse 25 29, 91054 Erlangen, Germany
Int J Hyg Environ Health 210:201-28. 2007..Protein adducts, especially Hb-adducts, as surrogates of DNA adducts measuring exposure as well as biochemical effect very specifically and sensitively are a still better means to ..
- Influence of the metabolic properties of human cells on the kinetic of formation of the major benzo[a]pyrene DNA adductsCaroline Marie
Laboratoire des Lésions des Acides Nucléiques, LCIB UMR E 3 CEA UJF, DRFMC, CEA Grenoble, 17 Avenue des Martyrs 38054 Grenoble Cedex 9, France
J Appl Toxicol 28:579-90. 2008..Some of them, including benzo[a]pyrene (B[a]P), are tumorigenic due to their ability to generate DNA adducts. In order to define potential biomarkers of B[a]P exposure, the aim of the study was to identify the major ..
- Elevated levels of the pro-carcinogenic adduct, O(6)-methylguanine, in normal DNA from the cancer prone regions of the large bowelA C Povey
Cancer Research Campaign Section of Genome Damage and Repair, Paterson Institute for Cancer Research, Manchester, M20 9BX, UK
Gut 47:362-5. 2000..The biological significance of this exposure is, as yet, unknown but in situ NOC formation is bacterially catalysed suggesting that NOC formation and potentially DNA alkylation will vary throughout the large bowel...
- Structures of 2-acetylaminofluorene modified DNA revisited: insight into conformational heterogeneitySatyakam Patnaik
Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, Rhode Island 02881, USA
Chem Res Toxicol 23:1650-2. 2010..The S/B/W-conformational heterogeneities were found to be sensitive to the nature of the flanking DNA sequence contexts and pH...
- Ochratoxin a causes DNA damage and cytogenetic effects but no DNA adducts in ratsAngela Mally
Department of Toxicology, University of Wurzburg, Germany
Chem Res Toxicol 18:1253-61. 2005..Oxidative DNA damage as a mechanism of OTA-dependent DNA damage is consistent with the absence of lipophilic DNA adducts as assessed by 32P-postlabeling analysis...
- Resistance of bulky DNA lesions to nucleotide excision repair can result from extensive aromatic lesion-base stacking interactionsDara A Reeves
Department of Chemistry, Department of Biology, New York University, New York, NY 10003, USA
Nucleic Acids Res 39:8752-64. 2011....
- The vital role of polymerase ζ and REV1 in mutagenic, but not correct, DNA synthesis across benzo[a]pyrene-dG and recruitment of polymerase ζ by REV1 to replication-stalled siteKeiji Hashimoto
Department of Pharmacological Sciences, State University of New York, Stony Brook, New York 11794 8651, USA
J Biol Chem 287:9613-22. 2012..This indicates that a non-Y family polymerase(s) can insert a nucleotide opposite BPDE-dG, but the subsequent extension from miscoding termini depends on REV1-polζ in a RAD18-dependent manner...
- Use of LC-MS/MS and stable isotopes to differentiate hydroxymethyl and methyl DNA adducts from formaldehyde and nitrosodimethylamineKun Lu
Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA
Chem Res Toxicol 25:664-75. 2012Formaldehyde is a known human and animal carcinogen that forms DNA adducts, and causes mutations. While there is widespread exposure to formaldehyde in the environment, formaldehyde is also an essential biochemical in all living cells...
- Probing the conformational heterogeneity of the acetylaminofluorene-modified 2'-deoxyguanosine and DNA by 19F NMR spectroscopyB P Cho
Department of Biomedical Sciences, College of Pharmacy, University of Rhode Island, Kingston 02881, USA
Biochemistry 38:7572-83. 1999..et al. (1997) J. Am. Chem. Soc. 119, 5384-5389]. The exclusive stacked nature of the AAF adducts may provide insight into why AAF adducts are more mutagenic and prone to repair than the nonacetylated AF adducts...
- Chemistry and structural biology of DNA damage and biological consequencesMichael P Stone
Department of Chemistry, Center in Molecular Toxicology, Vanderbilt Ingram Cancer Center, Vanderbilt University, Nashville, TN 37235, USA
Chem Biodivers 8:1571-615. 2011..The structural analysis of various DNA adducts reveals that conformational and chemical rearrangements and interconversions are a common theme...
- Site-specific radical formation in DNA induced by Cu(II)-H₂O₂ oxidizing system, using ESR, immuno-spin trapping, LC-MS, and MS/MSSuchandra Bhattacharjee
Laboratory of Toxicology and Pharmacology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA
Free Radic Biol Med 50:1536-45. 2011..The DMPO adduct formed is initially EPR active but subsequently is oxidized to the stable nitrone, which can then be detected by IST and further characterized by MS and MS/MS...
- Processing of anthracycline-DNA adducts via DNA replication and interstrand crosslink repair pathwaysR A Bilardi
Department of Biochemistry, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, Victoria 3086, Australia
Biochem Pharmacol 83:1241-50. 2012..of topoisomerase II, however many anthracyclines, including doxorubicin, are also capable of forming drug-DNA adducts. Anthracycline-DNA adducts present an unusual obstacle for cells as they are covalently attached to one DNA ..
- Influence of flanking sequence context on the conformational flexibility of aminofluorene-modified dG adduct in dA mismatch DNA duplexesNidhi Jain
Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI 02881, USA
Nucleic Acids Res 37:1628-37. 2009....
- Differential removal of DNA adducts derived from anti-diol epoxides of dibenzo[a,l]pyrene and benzo[a]pyrene in human cellsKristian Dreij
The Institute of Environmental Medicine, Division of Biochemical Toxicology, Karolinska Institutet, Box 210, S 17177 Stockholm, Sweden
Chem Res Toxicol 18:655-64. 2005..of their ultimate carcinogenic diol epoxide (DE) intermediates, differences in structural features of the DNA adducts, and differences in DNA adduct recognition and the subsequent lesion removal by nucleotide excision repair (NER)..
- The pyrrolobenzodiazepine dimer SJG-136 forms sequence-dependent intrastrand DNA cross-links and monoalkylated adducts in addition to interstrand cross-linksKhondaker M Rahman
Gene Targeted Drug Design Research Group, The School of Pharmacy, University of London, 29 39 Brunswick Square, London WC1N 1AX, UK
J Am Chem Soc 131:13756-66. 2009....
- Standardization and validation of DNA adduct postlabelling methods: report of interlaboratory trials and production of recommended protocolsD H Phillips
Institute of Cancer Research, Haddow Laboratories, Sutton, Surrey, UK
Mutagenesis 14:301-15. 1999..was to devise and test improved protocols of the 32P-postlabelling assay for the detection of carcinogen-DNA adducts. The intention was to reverse the drift of different investigators using increasingly divergent experimental ..
- The 32P-postlabeling assay for DNA adductsDavid H Phillips
Institute of Cancer Research, Brookes Lawley Building, Cotswold Road, Sutton, Surrey SM2 5NG, UK
Nat Protoc 2:2772-81. 200732P-postlabeling analysis is an ultrasensitive method for the detection and quantitation of carcinogen-DNA adducts. It consists of four principal steps: (i) enzymatic digestion of DNA to nucleoside 3'-monophosphates; (ii) enrichment of ..
- Validation of biomarkers for the study of environmental carcinogens: a reviewValentina Gallo
Department of Epidemiology and Public Health, Imperial College London, London, UK
Biomarkers 13:505-34. 2008..Our aim is to review published work on the validation of selected biomarkers: bulky DNA adducts, N-nitroso compounds, 1-hydroxypyrene, and oxidative damage to DNA...
- Adduct-specific monoclonal antibodies for the measurement of cisplatin-induced DNA lesions in individual cell nucleiBernd Liedert
Institut fur Zellbiologie, Universitatsklinikum, Essen Germany
Nucleic Acids Res 34:e47. 2006..we describe a new method to establish and characterize monoclonal antibodies (Mab) for structurally defined DNA adducts. The two major reaction products of cisplatin, the guanine-guanine (Pt-[GG]) and adenine-guanine (Pt-[AG]) ..
- Carcinogenic polycyclic aromatic hydrocarbon-DNA adducts and mechanism of actionWilliam M Baird
Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, Oregon 97331, USA
Environ Mol Mutagen 45:106-14. 2005..Thus, PAHs may also act through a promotional mechanism in addition to serving as tumor initiators. Previous studies on these mechanisms are described and summarized...
- Molecular dosimetry of N2-hydroxymethyl-dG DNA adducts in rats exposed to formaldehydeKun Lu
Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, North Carolina 27599, United States
Chem Res Toxicol 24:159-61. 2011..Our data clearly demonstrated that exogenous formaldehyde DNA adducts form in a highly nonlinear fashion, with a 21...
- Cisplatin: from DNA damage to cancer chemotherapyS M Cohen
Department of Chemistry, Massachusetts Institute of Technology, Cambridge 02139, USA
Prog Nucleic Acid Res Mol Biol 67:93-130. 2001..Continued efforts to understand the mechanism of genotoxicity of cisplatin are expected to lead to the discovery of new drugs and combinations for the improvement of cancer chemotherapy...
- Acrolein is a major cigarette-related lung cancer agent: Preferential binding at p53 mutational hotspots and inhibition of DNA repairZhaohui Feng
Department of Environmental Medicine, Pathology, and Medicine, New York University School of Medicine, Tuxedo, NY 10987, USA
Proc Natl Acad Sci U S A 103:15404-9. 2006..Acrolein (Acr) is abundant in CS, and it can directly adduct DNA. Acr-DNA adducts, similar to PAH-DNA adducts, induce predominantly G-to-T transversions in human cells...
- Overexpression of cMOAT (MRP2/ABCC2) is associated with decreased formation of platinum-DNA adducts and decreased G2-arrest in melanoma cells resistant to cisplatinBernd Liedert
Institute of Cell Biology, University of Essen, Germany
J Invest Dermatol 121:172-6. 2003..Kinetics of formation and elimination of platinum-DNA adducts suggest that the DNA repair capacity for Pt-d(GpG) adducts was not elevated in platinum drug-resistant melanoma ..
- 5-Azacytidine induced methyltransferase-DNA adducts block DNA replication in vivoH Kenny Kuo
Department of Biochemistry, Duke University, Durham, NC 27710, USA
Cancer Res 67:8248-54. 2007..These results imply that aza-C-induced MTase-DNA adducts block DNA replication in vivo. RecA-dependent X structures were also observed after aza-C treatment...
- Intra-hepatic arterial administration with miriplatin suspended in an oily lymphographic agent inhibits the growth of tumors implanted in rat livers by inducing platinum-DNA adducts to form and massive apoptosisMitsuharu Hanada
Pharmacology Research Laboratories, Dainippon Sumitomo Pharma Co, Ltd, Osaka, Japan
Cancer Chemother Pharmacol 64:473-83. 2009..We clarified the usefulness of miriplatin as an agent for transarterial chemoembolization...
- Site-specific incorporation of N-(deoxyguanosin-8-yl)-2-acetylaminofluorene (dG-AAF) into oligonucleotides using modified 'ultra-mild' DNA synthesisLudovic C J Gillet
Institute for Molecular Cancer Research, University of Zürich August Forel Strasse 7, 8008 Zurich, Switzerland
Nucleic Acids Res 33:1961-9. 2005..Our synthetic approach should facilitate comprehensive studies of the mechanisms of repair and mutagenesis induced by dG-AAF adducts in DNA and should be of general use for the incorporation of base-labile functionalities into DNA...
- The sequence dependence of human nucleotide excision repair efficiencies of benzo[a]pyrene-derived DNA lesions: insights into the structural factors that favor dual incisionsKonstantin Kropachev
Department of Chemistry, New York University, New York, NY 10003, USA
J Mol Biol 386:1193-203. 2009Nucleotide excision repair (NER) is a vital cellular defense system against carcinogen-DNA adducts, which, if not repaired, can initiate cancer development...
- Arsenite and its biomethylated metabolites interfere with the formation and repair of stable BPDE-induced DNA adducts in human cells and impair XPAzf and FpgTanja Schwerdtle
Institute of Food Chemistry and Toxicology, University of Karlsruhe, Postfach 6980, D 76128, Karlsruhe, Germany
DNA Repair (Amst) 2:1449-63. 2003..Altogether the results suggest that besides arsenite, especially the trivalent methylated metabolites may contribute to diminished NER at low concentrations...
- Adverse reproductive outcomes from exposure to environmental mutagensR J Sram
Laboratory of Genetic Ecotoxicology, Regional Institute of Hygiene of Central Bohemia, c o Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Videnska 1083, 142 20, Prague, Czech Republic
Mutat Res 428:203-15. 1999..Genotoxicity of urban air particles <10 microm (PM10) in in vitro system was determined by the analysis of DNA adducts. The highest DNA binding activity was observed in aromatic fraction, identifying DNA adducts of carcinogenic ..
- Endogenous versus exogenous DNA adducts: their role in carcinogenesis, epidemiology, and risk assessmentJames A Swenberg
Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina 27599, USA
Toxicol Sci 120:S130-45. 2011..known human carcinogens": formaldehyde, vinyl chloride (VC), and ethylene oxide (EO), each of which forms DNA adducts identical to endogenous DNA adducts in all individuals...
- A critical evaluation of DNA adducts as biological markers for human exposure to polycyclic aromatic compoundsRoger W L Godschalk
Department of Health Risk Analysis and Toxicology, University of Maastricht, 6200 MD Maastricht, The Netherlands
J Biochem Mol Biol 36:1-11. 2003..The successful applicability of DNA adducts as early endpoints depends on several criteria: i...
- Acrolein: sources, metabolism, and biomolecular interactions relevant to human health and diseaseJan F Stevens
Department of Pharmaceutical Sciences, Oregon State University, Corvallis, OR, USA
Mol Nutr Food Res 52:7-25. 2008..Acrolein adduction disrupts the function of these biomacromolecules which may result in mutations, altered gene transcription, and modulation of apoptosis...
- AlkB reverses etheno DNA lesions caused by lipid oxidation in vitro and in vivoJames C Delaney
Biological Engineering Division, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
Nat Struct Mol Biol 12:855-60. 2005..These reactions show a previously unrecognized chemical versatility of AlkB. In mammals, the corresponding AlkB homologs may defend against aging, cancer and oxidative stress...
- Associations of plasma aflatoxin B1-albumin adduct level with plasma selenium level and genetic polymorphisms of glutathione S-transferase M1 and T1S Y Chen
Columbia University School of Public Health, New York, NY 10032, USA
Nutr Cancer 38:179-85. 2000..This study provides insight into the dietary and genetic factors influencing AFB1-albumin adduct formation in an isolated population with high liver cancer mortality...
- DNA adduct formation in precision-cut rat liver and lung slices exposed to benzo[a]pyreneJeanine A Harrigan
Department of Pharmacology and Toxicology, State University of New York at Buffalo, Buffalo, New York 14214, USA
Toxicol Sci 77:307-14. 2004Chemical-DNA adducts provide an integrated measure of exposure, absorption, bioactivation, detoxification, and DNA repair following exposure to a genotoxic agent...
- Multiple ATR-Chk1 pathway proteins preferentially associate with checkpoint-inducing DNA substratesSeçil Yilmaz
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina, United States of America
PLoS ONE 6:e22986. 2011..We conclude that the association and accumulation of multiple checkpoint proteins with DNA structures indicative of DNA damage and replication stress likely contribute to optimal ATR-Chk1 DNA damage checkpoint responses...
- [Effects of CYP1A1 and GSTM1 gene polymorphisms and BPDE-DNA adducts on lung cancer]Chun Mei Chen
Laboratory of Environment Epigenetics, Institute of Environmental Health, College of Public Health, Zhejiang University Medical School, Hangzhou, Zhejiang 310058, P R China
Zhonghua Yi Xue Yi Chuan Xue Za Zhi 29:23-7. 2012To investigate the effect of CYP1A1 and GSTM1 genetic polymorphisms and BPDE-DNA adducts on lung tumorigenesis.
- Functional effect of polymorphisms in 15q25 locus on CHRNA5 mRNA, bulky DNA adducts and TP53 mutationsXavier Tekpli
Section for Toxicology, Department of Biological and Chemical Working Environment, National Institute of Occupational Health, Oslo, Norway
Int J Cancer 132:1811-20. 2013..were associated with differential levels of genetic alterations measured as the levels of hydrophobic DNA adducts in the adjacent histologically normal tissue of the lung cancer patients and as TP53 mutations in their lung ..
- Role of human CYP1A1 and NAT2 in 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine-induced mutagenicity and DNA adductsJ Bendaly
Department of Pharmacology and Toxicology, James Graham Brown Cancer Center, and Center for Environmental Genomics and Integrative Biology, University of Louisville School of Medicine, Louisville, KY, USA
Xenobiotica 39:399-406. 2009..05) following one-way analysis of variance. These results strongly support activation of PhIP by CYP1A1 with little effect of human NAT2 genetic polymorphism on mutagenesis and DNA damage...
- DNA adducts with antioxidant flavonoids: morin, apigenin, and naringinShohreh Nafisi
Department of Chemistry, Azad University, Central Tehran Branch IAUCTB, Tehran, Iran
DNA Cell Biol 27:433-42. 2008..10 x 10(3) M(-1). The affinity of ligand-DNA binding is in the order of apigenin > morin > naringin. DNA aggregation and a partial B- to A-DNA transition occurs upon morin, apigenin, and naringin complexation...
- The effect of dibenzo[a,1]pyrene and benzo[a]pyrene on human diploid lung fibroblasts: the induction of DNA adducts, expression of p53 and p21(WAF1) proteins and cell cycle distributionB Binkova
Laboratory of Genetic Ecotoxicology, Regional Institute of Hygiene of Central Bohemia, c o Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Videnska 1083, 142 20 Prague 4, Czech Republic
Mutat Res 471:57-70. 2000..The induction of p53 and p21(WAF1) protein occurred subsequent to the induction of DNA adducts. The DNA adduct levels correlated with both p53 (R=0.832, P<0.001 and R=0.859, P<0...
- Identification of three major DNA adducts formed by the carcinogenic air pollutant 3-nitrobenzanthrone in rat lung at the C8 and N2 position of guanine and at the N6 position of adenineVolker M Arlt
Institute of Cancer Research, Section of Molecular Carcinogenesis, Sutton, Surrey, United Kingdom
Int J Cancer 118:2139-46. 2006..Previously, we detected the formation of 3-NBA-derived DNA adducts in rodent tissues by 32P-postlabeling, all of which are derived from reductive metabolites of 3-NBA bound to ..
- Differences in conformational dynamics of [Pt3(HPTAB)]6+-DNA adducts with various cross-linking modesYanyan Zhu
College of Chemistry, Beijing Normal University, Beijing 100875, P R China
Nucleic Acids Res 37:5930-42. 2009..dynamics simulations and DNA conformational dynamics for a series of trinuclear platinum [Pt(3)(HPTAB)](6+)-DNA adducts [HPTAB = N,N,N',N',N'',N''-hexakis (2-pyridyl-methyl)-1,3,5-tris(aminomethyl) benzene], including three types ..
- DNA adducts in skin biopsies and 1-hydroxypyrene in urine of psoriasis patients and healthy volunteers following treatment with coal tarJ H J Roelofzen
Department of Dermatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Toxicol Lett 213:39-44. 2012..In this study, levels of urinary 1-hydroxypyrene and PAH-DNA adducts in the skin were studied in psoriatic patients and healthy volunteers...
- DNA adducts of decarbamoyl mitomycin C efficiently kill cells without wild-type p53 resulting from proteasome-mediated degradation of checkpoint protein 1Ernest K Boamah
Department of Biological Sciences, Hunter College and the Graduate Center, City University of New York, 695 Park Avenue, New York, NY 10065, USA
Chem Res Toxicol 23:1151-62. 2010..the level of total ubiquitinated proteins without increasing proteasome activity, suggesting that DMC mediated DNA adducts facilitate signal transduction to a pathway targeting cellular proteins for proteolysis...
- Breast cancer chemoprevention: risk-benefit effects of the antioestrogen tamoxifenKaren Brown
Cancer Biomarkers and Prevention Group, The Biocentre, University of Leicester, University Road, Leicester, LE1 7RH, UK
Expert Opin Drug Saf 1:253-67. 2002....
- DNA adducts in tumour, normal peripheral lung and bronchus, and peripheral blood lymphocytes from smoking and non-smoking lung cancer patients: correlations between tissues and detection by 32P-postlabelling and immunoassayErika Gyorffy
National Institute of Environmental Health, Jozsef Fodor National Center for Public Health, Budapest, H 1097 Hungary
Carcinogenesis 25:1201-9. 2004Smoking is a major risk factor for lung cancer. This comparative study of smoking-related carcinogen-DNA adducts in pulmonary tissues and peripheral blood lymphocytes aims to further explore the primary DNA damaging processes by ..
- DNA interstrand crosslinks: natural and drug-induced DNA adducts that induce unique cellular responsesORLANDO D SCHARER
Institute of Molecular Cancer Research, University of Zurich, August Forel Strasse 7, 8008 Zurich, Switzerland
Chembiochem 6:27-32. 2005
- Modulation of gene expression and DNA adduct formation in HepG2 cells by polycyclic aromatic hydrocarbons with different carcinogenic potenciesYvonne C M Staal
Department of Health Risk Analysis and Toxicology, Maastricht University, The Netherlands
Carcinogenesis 27:646-55. 2006..Our data indicate that discrimination of high and low carcinogenic PAHs by gene expression profiling is feasible. Also, the carcinogenic PAHs induce several pathways that were not affected by the least carcinogenic PAHs...
- Bulky DNA adducts, 4-aminobiphenyl-haemoglobin adducts and diet in the European Prospective Investigation into Cancer and Nutrition (EPIC) prospective studyMarco Peluso
Cancer Risk Factor Branch, Analytical and Biomolecular Cytology Unit, CSPO Scientific Institute of Tuscany, Florence, Italy
Br J Nutr 100:489-95. 2008..and Nutrition (EPIC) cohort the association between dietary items (food groups and nutrients) and aromatic DNA adducts and 4-aminobiphenyl-Hb adducts...
- Mutagenic events in Escherichia coli and mammalian cells generated in response to acetylaminofluorene-derived DNA adducts positioned in the Nar I restriction enzyme siteXingzhi Tan
Laboratory of Chemical Biology, Department of Pharmacological Sciences, State University of New York at Stony Brook, Stony Brook, New York 11794 8651, USA
Biochemistry 41:14255-62. 2002..3-21%, the higher value at G(2). We conclude from this study that the mutation potential of dG-AAF and dG-AF depends on the structure of the adduct, the sequence context of the lesion, and the host cell used for the experiment...
- Dynamic conformational heterogeneities of carcinogen-DNA adducts and their mutagenic relevanceBongsup P Cho
Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, RI 02882, USA
J Environ Sci Health C Environ Carcinog Ecotoxicol Rev 22:57-90. 2004..Results from such experiments should provide an accurate account of how a single chemically homogenous adduct gives rise to complex multiple mutations, the earliest step in the induction of cancer...
- Interactive effects of nrf2 genotype and oltipraz on benzo[a]pyrene-DNA adducts and tumor yield in miceMinerva Ramos-Gomez
Department of Environmental Health Sciences, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, MD 21202, USA
Carcinogenesis 24:461-7. 2003..To evaluate the role of nrf2 genotype on B[a]P disposition, levels of B[a]P-DNA adducts were measured as tetrols released from DNA isolated from target (forestomach) and non-target tissues (liver) of ..
- cis-Diammine(pyridine)chloroplatinum(II), a monofunctional platinum(II) antitumor agent: Uptake, structure, function, and prospectsKatherine S Lovejoy
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
Proc Natl Acad Sci U S A 105:8902-7. 2008..cDPCP-DNA adducts are removed by the nucleotide excision repair apparatus, albeit much less efficiently than bifunctional ..
- Aromatic DNA adducts and risk of gastrointestinal cancers: a case-cohort study within the EPIC-SpainAntonio Agudo
Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology ICO, Av Gran Vía 199 203, L Hospitalet de Llobregat, Spain
Cancer Epidemiol Biomarkers Prev 21:685-92. 2012..Activated metabolites of these compounds may bind to DNA forming bulky adducts...
- Mutagenesis and repair induced by the DNA advanced glycation end product N2-1-(carboxyethyl)-2'-deoxyguanosine in human cellsDaniel Tamae
Division of Molecular Medicine, Beckman Research Institute of the City of Hope, 1500 East Duarte Road, Duarte, California 91010, United States
Biochemistry 50:2321-9. 2011..0001). This suggested the involvement of an NER-dependent mutagenic process in response to critical levels of DNA damage, possibly mediated by error-prone Y-family polymerases...
- Benzo[a]pyrene-7,8-quinone-3'-mononucleotide adduct standards for 32P postlabeling analyses: detection of benzo[a]pyrene-7,8-quinone-calf thymus DNA adductsNarayanan Balu
Environmental Carcinogenesis Division, Office of Research and Development, U S Environmental Protection Agency, Research Triangle Park, NC 27711, USA
Anal Biochem 355:213-23. 2006..Chem. Res. Toxicol. 17 (2004) 827-838). However, the identification of BPQ-DNA adducts by 32P postlabeling methods from in vitro and in vivo exposures required 3'-monophosphate derivatives of BPQ-dG,..
- DNA adducts and oxidative DNA damage induced by organic extracts from PM2.5 in an acellular assayJan Topinka
Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Videnska 1083, 14220 Prague 4, Czech Republic
Toxicol Lett 202:186-92. 2011..8-oxodG, levels) induced by EOMs in an acellular assay of calf thymus DNA coupled with ³²P-postlabeling (DNA adducts) and ELISA (8-oxodG) in the presence and absence of microsomal S9 fraction were employed...
- Repair of laser-localized DNA interstrand cross-links in G1 phase mammalian cellsParameswary A Muniandy
Laboratory of Molecular Gerontology, NIA, National Institutes of Health, Baltimore, Maryland 21224, USA
J Biol Chem 284:27908-17. 2009..DDB2 accumulation at sites of cross-link repair is a marker for the start of the second repair cycle...
- Polycyclic aromatic hydrocarbons and birth outcomes in Mexico CityMARIE SYLVIA O'NEILL; Fiscal Year: 2013..We will obtain biomarkers relevant to PAH exposure (DNA adducts) in blood samples provided by participants monthly during their pregnancies, and umbilical cord blood obtained ..
- Enterococcus faecalis, Colorectal Cancer, and Bystander EffectsMark M Huycke; Fiscal Year: 2012..The generation of mutagenic exocyclic DNA adducts and DNA double strand breaks (DSBs) in target cells by the macrophage-induced BSE will be measured using LC/MS/..
- MOLECULAR MECHANISMS OF COMPLEX MIXTURE TOXICITYAlvaro Puga; Fiscal Year: 2013..polymerase II to the Cyp1a1 promoter, block BaP-inducible gene expression and stimulate the formation of BPDE-DNA adducts. Similarly, sustained exposure to low doses of chromium leads to gradual changes in histone marks and signal ..
- CHEMISTRY AND BIOLOGY OF PLATINUM ANTICANCER DRUGSStephen J Lippard; Fiscal Year: 2013..Nucleosomes, the building blocks of chromosomes, will be constructed with site-specific Pt-DNA adducts and structurally characterized in solution by footprinting and in the solid state by X-ray crystallography...
- Functional roles of Nrf2 and NQO1 genetic variants in hyperoxic lung injury-ARDSBhagavatula Moorthy; Fiscal Year: 2013..or controls will be analyzed for the presence of SNPs, F2- isoprostanes/isofurans, levels of bulky oxidative DNA adducts, and protein oxidation products...
- Molecular mechanisms of cytochrome P4501A regulation by hyperoxiaBhagavatula Moorthy; Fiscal Year: 2010..that CYP1A1 enzymes play a protective role against cell toxicity in cultured cells, and that oxidative DNA adducts play a mechanistic role in contributing to oxygen mediated toxicities leading to apoptosis and/or necrosis...
- Prevention of Esophageal Cancer with BerriesGary Stoner; Fiscal Year: 2013..the effects of dietary anthocyanins and PEITC, alone and in combination, on the formation of NMBA-induced DNA adducts in rat esophagus as well as their effects on the expression of genes associated with cell proliferation, ..
- DNA Repair of Endogenous Lesions in CarcinogenesisRabindra Roy; Fiscal Year: 2010..repair of endogenous DNA damage, including oxidized bases (Reactive Oxygen Species (ROS)-induced) and cyclic DNA adducts (enal-induced), plays a critical role in carcinogenesis...
- Lipid peroxidation product induced DNA damage in the p53 gene and liver cancerERIC MOON SHONG M TANG; Fiscal Year: 2010..We will determine how 4-HNE-DNA adducts in the p53 gene are processed, and the role of the p53 gene in aldehyde-mediated inhibition of DNA repair in ..
- Cancer induction in the ovary by an environmental pollutant, dibenzo[a,l]pyreneKun Ming Chen; Fiscal Year: 2013..Presence of DNA adducts in tissues exposed to environmental carcinogens is crucial to the initiation of the carcinogenic process, and ..
- SPLENIC TOXICITY OF ANILINEM Firoze Khan; Fiscal Year: 2010..Aim 2 will examine the role of oxidative DNA damage and repair, malondialdehyde-DNA adducts, DNA methylation, and mutations in the tumor suppressor gene p53 in aniline-induced splenic toxicity...
- Genomic profiling of yeast resistance to AFB1, a P450-activated carcinogenMICHAEL THOMAS FASULLO; Fiscal Year: 2013..resistance and sensitivity, and provide insights into how recombinational repair processes actively tolerate DNA adducts. The strain collections will be made available to the scientific community and will be a valuable resource for ..
- Detoxification of Electrophilic Chemical Threat Agents by Nucleophilic ScavengersMichael C MacLeod; Fiscal Year: 2010..The primary strategies to be developed in this Project will block the ability of SNMs to form DNA adducts in exposed cells...
- RNA Polymerase Transcription Past DNA AdductsDavid A Scicchitano; Fiscal Year: 2013..We will: (1) investigate RNA polymerase II transcription past select DNA adducts;(2) determine the base sequence of the mRNA produced via bypass of each lesion;and (3) examine DNA repair, ..
- Development of Novel Agents Targeting Genome Stability and Maintenance for TreatiJohn J Turchi; Fiscal Year: 2013..Cisplatin and carboplatin both impart their chemotherapeutic effect by the formation of Pt-DNA adducts which block DNA replication and transcription culminating in apoptosis...
- 2-Amino-9H-pyrido[2,3-b]indole: a potential colorectal carcinogen formed in tobacRobert J Turesky; Fiscal Year: 2013..In Aim 2, the genotoxicity of AaC in the colorectum of C57BL/6N mice will be determined, by measurement of DNA adducts and aberrant crypt foci, as early biomarkers of neoplasia...
- Chemoprevention by black raspberry in oral cancer induced by DB[a,l]P in miceKARAM E EL-BAYOUMY; Fiscal Year: 2013..induced by DB[a,l]P and its diol epoxide are very similar, consistent with the formation of stable covalent DNA adducts (Preliminary Results)...
- Role of cytochrome P4501B1 in oxygen-mediated pulmonary injuryBhagavatula Moorthy; Fiscal Year: 2013..lung injury by inducing CYP1A enzymes;and (iii) exacerbating enhanced formation of ROS-mediated oxidative DNA adducts derived from 8- 5'cyclopurines or lipid peroxidation products, resulting in oxygen-mediated injury...
- ELECTROCATALYTIC STUDIES OF TOXIC POLLUTANT ACTIVATIONJames F Rusling; Fiscal Year: 2013..Similar films on nanoparticles provide samples for LC-MS analysis of metabolite-DNA adducts. These approaches will also provide enzyme specificities, site specificities of DNA damage, and pathways of DNA ..
- Intra- and Extra-Chromosomal Probes for Mutagenesis by CarcinogensJohn M Essigmann; Fiscal Year: 2013..Two key features of the project are (1) its emphasis on in vivo analysis of the biology of DNA adducts, many of which are produced by human carcinogens and (2) the emphasis on rigorous synthetic methodology for ..
- Aflatoxin B1 hepatocarcinogenesis in the mGSTA3-/- mouseStewart Sell; Fiscal Year: 2013..of loss of the mGSTA3 on AFB1-induced toxicity, by measuring the steps of AFB1 metabolism, the levels of AFB1-DNA adducts and extent of oxidative damage in liver tissues...
- INFIDELITY OF CYTOSINE METHYLATION AND HUMAN CANCERLawrence C Sowers; Fiscal Year: 2013..that reactive molecules generated by activated neutrophils and eosinophils can generated an array of DNA adducts. Among these products are 5-chlorocytosine (5ClC) and 5-bromocytosine (5BrC)...
- Aldo-Keto Reductases and PAH Metabolism/ActivationTrevor M Penning; Fiscal Year: 2013..Thus, in addition to PAH diol-epoxide-DNA adducts, oxidative DNA lesions may contribute to lung cancer initiation...
- Synthesis, StructUre and Replication of Carcirogen-Modified OligonucleotidesCarmelo J Rizzo; Fiscal Year: 2013..HCA-DNA adducts have been detected from human tissue after exposure to dietary relevant doses...
- Reactive oxygen species and Genomic Instability in CMLMartin Sattler; Fiscal Year: 2012..Reactive oxygen species (ROS) have already been shown to generate DNA adducts and cause oxidative DNA damage, which can result in genomic mutations...
- NYU Lung Cancer Biomarker CenterWilliam N Rom; Fiscal Year: 2013..lung cancer from high-risk controls with L, Showe (Wistar, UPenn), M-s Tang and colleagues demonstrated DNA adducts occurred at hot spot mutation sites in p53 and K-ras, and that poor repair contributed to adduct persistence...
- DNA cross-linking by diepoxybutaneNatalia Y Tretyakova; Fiscal Year: 2013..of mutagenesis and cytotoxicity resulting from BD exposure by providing key information about bifunctional DEB-DNA adducts, including their formation in vivo following exposure to BD, their effects on DNA structure, mispairing ..
- The role of Mc1r in melanocytic UV-induced DNA damage and repair responsesJOHN A DORAZIO; Fiscal Year: 2013..Southwestern blotting, hOGG1-adapted Comet assay, TBARS assay, and direct quantification of oxidative DNA adducts by GC/MS)...
- MOLECULAR EPIDEMIOLOGY OF LUNG CANCERChu Chen; Fiscal Year: 2010..effect is the DNA damage produced by the generation of reactive oxygen species and the formation of DNA adducts. Since the majority of persons who smoke tobacco do not develop lung cancer, it is possible that those who do ..
- Sequence Distribution of Tobacco Carcinogen-DNA AdductsNatalia Y Tretyakova; Fiscal Year: 2012..methylation and the local DNA sequence context control the rates of formation and repair of tobacco carcinogen-DNA adducts. Guided by strong preliminary data, this hypothesis will be tested by pursuing the following four specific aims:..
- In vivo detection and genome-wide location analysis of DNA-adductsStephen B Howell; Fiscal Year: 2013DESCRIPTION (provided by applicant): DNA adducts are the hallmark and most common form of DNA damage in the cell...
- Pharmacokinetics and Metabolism of Oxidized CurcuminClaus Schneider; Fiscal Year: 2013..shown that these metabolites contribute to the regulation of cellular antioxidant response and form covalent DNA adducts. The goal of this grant application is to characterize pharmacokinetics, tissue distribution, and metabolism of ..
- Heat Shock Protein-Induced Protection Against Cisplatin-Induced Hair Cell DeathTIFFANY GRAY BAKER; Fiscal Year: 2013..Cisplatin causes cell death by forming DNA adducts and increasing the pool of reactive oxygen species (ROS) in cells...
- Breast Cancer Chemoprevention StrategiesRamesh C Gupta; Fiscal Year: 2010..Chromatographic similarity with reference oxidative adducts suggests that tissue DNA adducts originated from free radical-mediation...
- Mutagenesis of p53 by reactive PAH and ROSJEFFREY M FIELD; Fiscal Year: 2012..A critical step in multi-stage carcinogenesis is the mutagenic event that results from the formation of DNA adducts. There are three principle routes of metabolic activation of PAH resulting in the formation of diol- epoxides, ..
- Biomarkers of toxic response to low nicotine cigarette smokeAndrew Strasser; Fiscal Year: 2012..that have been used are urinary isoprostanes to monitor oxidative stress, and the analysis of B[a]P-derived DNA adducts in leukocytes...
- A Novel Carcinogen-Induced Cell Cycle CheckpointCyrus Vaziri; Fiscal Year: 2013..application is to elucidate the roles of an E3 ubiquitin ligase termed 'Rad18'in tolerance of bulky DNA adducts (such as B[a]P- and UV-induced lesions) via Trans-Lesion Synthesis (TLS) and in repair of Double Strand Break (..
- Mechanisms of selective excision and oxidative repair of alkylated DNAManel Camps; Fiscal Year: 2013..Our studies have at least three direct clinical implications. First, etheno-DNA adducts likely play a role in the etiology of cancer associated with chronic inflammation, and thus results on eA ..
- Chemical markers of heterocyclic aromatic amines for human biomonitoringRobert J Turesky; Fiscal Year: 2011..will establish noninvasive chemical markers of HAAs, by measuring HAAs in hair, blood protein adducts, and DNA adducts in long-lived white blood cells, as surrogate biomarkers for target sites of cancer risk in humans who ..
- Mechanisms for Benzo(a)pyrene-Induced Colon Cancer Exacerbation by Dietary FatAramandla Ramesh; Fiscal Year: 2013..A linked hypothesis is that B(a)P effects are secondary to production of epoxide or quinones some of which form DNA adducts that cause genotoxicity...
- New biomonitoring methodologies to measure DNA adducts in human tissuesRobert J Turesky; Fiscal Year: 2013..by applicant): The objective of this proposal is to develop new biomonitoring methodologies designed to measure DNA adducts in tissues of humans exposed to chemical carcinogens...
- Aromatic Amine-DNA Lesions: Mutagenicity and RepairSuse Broyde; Fiscal Year: 2013..Among the plethora of DNA adducts, it is essential to identify the most hazardous ones for purposes of biomonitoring and assessing the exposure ..
- Molecular mechanism of cytochrome P4501A1 expression.Bhagavatula Moorthy; Fiscal Year: 2013..carcinogenesis, and that a CYP1A2-dependent MC metabolite(s) contributes to the formation of sequence- specific DNA adducts on the regulatory regions of the CYP1A1 promoter [e.g...
- Targeting the ERCC1/XPF nuclease for cancer therapyJohn J Turchi; Fiscal Year: 2012..Both cisplatin and carboplatin impart their chemotherapeutic effect by the formation of intrastrand Pt-DNA adducts. These adducts are repaired by the nucleotide excision repair (NER) pathway which relies on the ERCC1/XPF ..
- Prophylactic Use of Vitamin E for Prevention of Occupational PAH-Induced DamageDebbie Mustacich; Fiscal Year: 2009..Levels of BP-DNA adducts in cigarette smokers are decreased by vitamin E (a-tocopherol) administration...
- Coordinating Translesion DNA Synthesis Opposite Damaged DNARobert L Eoff; Fiscal Year: 2013..These so-called replicative DNA polymerases are often less able to bypass DNA adducts. Other specialized polymerases possess lesion bypass abilities that can aid the replication fork when it ..
- Targeting nucleotide excision repair in combination cancer therapyJohn J Turchi; Fiscal Year: 2013..Pt agents impart their therapeutic effect by the formation of Pt-DNA adducts, which block DNA replication and transcription...
- Bypass of DNA lesions by translesion synthesis in yeastLouise Prakash; Fiscal Year: 2013..To elucidate the mechanisms that govern replicative bypass of DNA adducts in eukaryotes including in humans, the proposed studies will utilize the yeast Saccharomyces cerevisiae...
- The role of heterocyclic aromatic amines in breast cancerRobert J Turesky; Fiscal Year: 2010..Immunohistochemistry (IHC) and 32P-postlabeling are two principal bioanalytical techniques used to measure DNA adducts, biomarkers of genetic damage...
- Excision of Carcinogen-DNA Adducts in NucleosomesNicholas E Geacintov; Fiscal Year: 2013..remarkable differences in the relative excision efficiencies of different, stereochemically well defined PAH-DNA adducts by the human nucleotide excision repair (NER) system in whole cell extracts...
- Translesion DNA synthesis in humansLouise Prakash; Fiscal Year: 2012..DNA lesions to be studied include UV photoproducts, and DNA adducts such as 1,N6-ethenodeoxyadenosine, 1,N2-propano-2'-deoxyguanosine, and (+) trans-dG-N2- benzo[a]pyrene ..
- Polymerase Interactions with Carcinogen-modified DNAF Peter Guengerich; Fiscal Year: 2013..solfataricus, Dpo1, Dpo2, Dpo3, and Dpo4, including their roles in normal replication and past several DNA adducts, as well as defining the role of the heterotrimeric PCNA protein in this organism...
- Molecular dosimetry of endogeneous genotoxinsIAN ALEXANDER BLAIR; Fiscal Year: 2010..Aim 4. To quantify endogenous lipid hydroperoxide-derived DNA-adducts, RNA- adducts, GSH-adducts as potential cancer biomarkers in animal models of colon cancer and in human colon tissue. ..
- Carcinogenic Metabolites Formed from AntiestrogenJudy L Bolton; Fiscal Year: 2013..Initial model studies with deoxynucleosides and DNA will allow characterization of stable DNA adducts, analysis of depurinating adducts, as well as determination of DNA oxidation...
- Measurements of BPDE-DNA adducts by solid state nonopore and deep sequencing (PQFarhad Kosari; Fiscal Year: 2013Measurements of BPDE-DNA adducts by solid state nanopore and deep sequencing (PQ3) Potent carcinogen Benzo[a]pyrene (BaP) is found in heavily polluted air, smoked food, and tobacco smoke...
- Investigating the Role of a Lifestyle Intervention on Novel Estrogen BiomarkersKerryn W Reding; Fiscal Year: 2011..within the catechol estrogen (CE) pathway, in particular hydroxy estrogen (HE) quinones, are capable of forming DNA adducts which may lead in certain instances to DNA mutations...
- Roles of the Smc5-Smc6 Holocomplex in Genome StabilityMichael N Boddy; Fiscal Year: 2013..Smc5-Smc6 in (i) promoting meiotic chromosome segregation at the MI division, (ii) the processing of protein-DNA adducts in a pathway parallel to Tdp1, and (iii) the resolution of DNA structures arising during the restart of ..
- Carcinogen-DNA Adducts: Topology, Conformation and Repair (Renewal)Suse Broyde; Fiscal Year: 2013..However, it has recently been shown that several of the bulky DNA adducts that they produce after metabolic activation to diol epoxides, are resistant to nucleotide excision repair (NER)..
- Polycyclic Aromatic Hydrocarbons And Male Reproductive HealthHUEIWANG ANNA COOK JENG; Fiscal Year: 2010..Semen will be collected to assess sperm quality and DNA integrity, and PAH-DNA adducts. Features of this design include efficient control for confounding factors, accurate exposure ascertainment, ..
- DNA Repair Capacity and Risk of Pre-malignant Lesion in Lung EpitheliumHua Zhao; Fiscal Year: 2009..ROS-caused base damages are mainly repaired by base excision repair (BER) and nucleotide excision repair (NER);DNA adducts caused by MPO- related carcinogen activation are repaired by NER...
- Curcumin inhbits BPDE-induced damage by lowering the threshold of p53 activationERICA NICOLE ROGERS; Fiscal Year: 2011..Because global genomic repair (GGR) removes most BPDE-DNA adducts in a p53-dependent manner, Specific aim 2 will use immunoslot blot, [32P]-postlabeling, and UvrABC mediated ..
- Role of HDAC6 in platinum resistance of non-small cell lung cancerXIAOHONG MARY ZHANG; Fiscal Year: 2013..Given the fact that MSH2 serves as a sensor for cisplatin-induced DNA adducts and loss of MSH2 causes cisplatin resistance, we hypothesize that down-regulation of MSH2 protein level and its ..
- GENOTOXICITY IN CYP1A2 DEFICIENT TRANSGENIC MICEDaniel Nebert; Fiscal Year: 2002..Chronically, ABP causes bladder ABP-DNA adducts and tumor formation as the consequence of hepatic CYP1A2 and N-acetyltransferase (NAT2) levels, as well as ..
- AFLATOXIN DNA ADDUCTS DETECTED BY MONOCLONAL ANTIBODIESJohn Groopman; Fiscal Year: 1992..study, we propose to: (1) Produce and characterize monoclonal antibodies to detect the major aflatoxin-DNA adducts: AFB1-N7-Gua and AF-FaPyr. Two strategies for antigen production will be used...
- Isomeric HRT estrogen-DNA adducts: Structure and RepairNicholas Geacintov; Fiscal Year: 2009..is the most significant metabolite among all three equine estrogens, and that it forms unusual cyclic, stable DNA adducts in vitro, in rat mammary tissue model systems, and in human breast tissue...
- MOLECULAR MECHANISMS OF HYDROCARBON/DNA INTERACTIONSWilliam Baird; Fiscal Year: 1999..are to determine how PAH bind to DNA in mammalian cells and to establish the relationship between specific PAH-DNA adducts and the induction of mutations and cancer...
- MECHANISM OF CHROMIUM CARCINOGENICITYKAREN WETTERHAHN; Fiscal Year: 1993..2) Chromium (VI)-induced DNA lesions, in the form of DNA strand breaks, DNA cross-links, chromium-DNA adducts and radical-DNA adducts, which result from the attack f "active intermediates" formed during the metabolism of ..
- Metabolism and Detoxification of Base PropenalsSanjay Srivastava; Fiscal Year: 2007..concentrations BPs are cytotoxic and cytostatic, whereas at low concentrations they form potentially mutagenic DNA adducts. Propenal-derived DNA adducts have been detected in high abundance in normal and cancerous human tissues and it ..
- HUMAN MISMATCH REPAIR IN CHEMICAL CARCINOGENESISGuo Min Li; Fiscal Year: 2001..Environmental carcinogens covalently modify DNA to form carcinogen-DNA adducts, which induce mutations that initiate carcinogenesis...
- ULTRASENSITIVE METHODS FOR HUMAN DNA ADDUCT QUANTITATIONJames Swenberg; Fiscal Year: 2000b>DNA adducts are believed to be a major source of the mutations involved in carcinogenesis...