Division of Chemical Toxicology

Program, 236th ACS National Meeting, Philadelphia, PA, August 17-21, 2008

Program Chair, Kent Gates

Sunday Morning

Structural Biology of DNA Damage and Repair

M. P. Stone, Organizer

8:10 -1. Interconversion of the cis-5R,6S- and trans-5R,6R-thymine glycol adducts in duplex DNA. M. P. Stone, K. L. Brown, T. Adams, V. Jasti, A. K. Basu.

8:40 -2. Crystal structure of DNA repair protein AlkD reveals a new protein architecture for locating and excising alkylpurines from DNA. E. H. Rubinson, Z. Wawrzak, A. H. Metz, J. O'Quin, B. F. Eichman

9:25 - Intermission.

9:40 -3. Interrogation, recognition and repair of damaged bases in DNA. A. Banerjee, J. C. Fromme, S. Jiralerspong, C. T. Radom, S. D. Bruner, S. J. Chung, W. Yang, M. Karplus, G. L. Verdine

10:25 -4. Enzymatic detection of uracil in DNA. J. T. Stivers

11:10 -5. DNA base excision repair initiation from the structural biochemistry of N-glyocsylases and endonucleases that recognize and excise DNA base damage. J. A. Tainer

Sunday Afternoon

Founders Award Symposium

K. S. Gates and L. J. Marnett, Organizers

2:00 - Introductory Remarks.

2:10 -6. Mechanisms of furan toxicity and carcinogenicity. L. A. Peterson

2:45 -7. Lipid Affinity Tag Substrates: ω-Alkynes as Probes for Lipid-Derived Electrophile Protein Adducts. K. A. Tallman, H -Y. Kim, R. Serwa, D. C. Liebler, N. A. Porter

3:20 -8. Mechanisms of protein tyrosine nitration in hydrophilic and hydrophobic biocompartments. R. Radi

3:55 -9. Design of DNA damaging agents that block DNA repair and disrupt cancer specific cellular signaling programs. J. M. Essigmann

4:30 -10. Lipid and DNA aldehydes as mediators of cellular responses to oxidative damage. L. J. Marnett

Monday Morning

General Papers: Young Investigator Session

K. S. Gates, Organizer

8:30 -11. General theory of toxicity. E. P. Nwosu

8:45 -12. Developing single nanoparticle optics and in vivo assays for real-time characterization of transport and biocompatibility of nanomaterials . K. J. Lee, P. D. Nallathamby, L. M. Browning, X. N. Xu

9:00 -13. Enhanced identification of biotin-derivatized peptides. P. G. Slade, M. V. Williams, J. S. Wishnok, S. R. Tannenbaum

9:15 -14. 1,N²-Ethenodeoxyguanosine adduct structure-function relationships: Comparing solution structure with polymerase structure. G. Shanmugam, I. D. Kozekov, F. P. Guengerich, C. J. Rizzo, M. P. Stone

9:30 -15. Atom site selectivity in DNA alkylation by primary diazonium ions . X. Lu, J. C. Fishbein

9:45 -16. Examination of reactive oxygen species as general signaling agents of dithiolethiones and the biochemical repercussions of their action. R. Holland, M. Velayutham, A. Hawkins, A. L. Eggler, J. L. Zweier, D. Fabris, A. D. Mesecar, T. W. Kensler, J. C. Fishbein

10:00 - Intermission.

10:15 -17. S-nitrosation regulates signaling in breast cancer. K. Pant, H. Saito-Benz, J. Li, F. M. White, S. R. Tannenbaum

10:30 -18. Influence of alkylating cytotoxins and chemotherapy drugs on cellular redox enzymes. X. Liu, S. J. Sturla

10:45 -19. In vitro studies of nimesulide idiosyncratic hepatotoxicity: Diiminoquinone formation and its conjugation. F. Li, M. D. Chordia, T. Huang, T. L. Macdonald

11:00 -20. Selective enrichment and analysis of nitrated proteins from iNOS activated mouse macrophages. K. E. Schlicht, J. S. Wishnok, S. R. Tannenbaum

11:15 -21. Solution Structures of Trans-4-Hydroxynonenal Derived 1,N²-dG Adduct in Oligodeoxynucleotides: Insights into Mutagenicity. H. Huang, H. Wang, A. Kozekova, C. J. Rizzo, M. P. Stone

11:30 -22. The contribution of key enzyme-substrate interactions to the cytochrome P450 catalyzed dehydrogenation of tamoxifen metabolites and the role of P450 conformational dynamics during tamoxifen metabolism. K. Shahrokh, G. S. Yost, T. E. Cheatham III?

Monday Afternoon

Chemical Biology of Epigenetics

N. Tretyakova and L. Sowers, Organizers

1:30 - Introductory Remarks.

1:40 -23. DNA methylation can be monitored by isotope tracers and GC/MS. L. Sowers, J. Herring

1:55 -24. Endogenous cytosine methylation influences the formation and repair of DNA adducts at CpG dinucleotides. N. Tretyakova, R. Guza, B. Matter

2:25 -25. Genetics and epigenetics of metal carcinogenesis. A. Zhitkovich

2:55 - Intermission.

3:05 -26. Inflammation mediated DNA damage induces epigenetic changes . L. Sowers, V. V. Lao

3:20 -27. Impact of carcinogen-DNA adducts on DNA methylation. N. E. Geacintov, E. S. Gromova

3:50 -28. DNA methylation inhibitors for the treatment of cancer . A. S. Yang

Monday Evening

Division of Chemical Toxicology Sci-Mix Symposium

K. S. Gates, Organizer

6:00 - 10:00.

Abstract numbers: 39-43, 46, 47, 52-54, 56, 57, 60-62, 72, 74-77, 82-88. See General Posters for listings of Authors and Titles.

Tuesday Morning

Drug Safety

N. A. Meanwell and F. P. Guengerich, Organizers

8:30 - Introductory Remarks.

8:40 -29. Prediction of cytochrome P450-based drug-drug interactions from in vitro information. R. S. Obach

9:30 -30. Grapefruit: A food that potently impairs intestinal drug metabolism and uptake transport clinically. D. G. Bailey

10:20 -31. Pregnane X receptor: Structure and binding properties of xenobiotics . M. A. Sinz

11:10 -32. Humanized mouse models to predict chemical safety and metabolism. F. J. Gonzalez, X. Ma, Q. Yang, J. R. Idle

Tuesday Afternoon

Cytochrome P450 Structure, Function, and Mechanism

F. P. Guengerich Organizer

1:30 -33. Recent advances in structural characterization of drug metablizing P450 monooxygenases. E. F. Johnson, S. Sansen, C. D. Stout

2:20 -34. Mechanism-based inactivation of human cytochrome P450s . P. F. Hollenberg, H -L. Lin, U. M. Kent

3:10 -35. Structure and function of cytochrome P450 enzymes: dynamics of catalytic steps in oxidation of drugs and model substrates. F. P. Guengerich, C. D. Sohl, E. M. Isin, R. L. Eoff

4:00 -36. What do industrial medicinal chemists need to know about cytochrome P450 R. E. White

Tuesday Evening

General Posters

K. S. Gates, Organizer

6:00 - 10:00

38. Absolute quantification assay for measuring protein tyrosine kinase and phosphatase activity by stable isotope dilution liquid chromatography/ tandem mass spectrometry. E. Ciccimaro, I. A. Blair

39. Absolute quantification of oxidative modifications on apoA-I protein by liquid chromatography/tandem mass spectrometry. K. Rangiah, E. Ciccimaro, I. Parastatidis, H. Ischiropoulos, M. P. Reilly, S. J. Shah, I. A. Blair

40. Analysis of formaldehyde induced lysine-deoxyguanosine cross-links by mass spectrometry. K. Lu, J. Swenberg

41. Analysis of gene expression changes of drug metabolizing enzymes in the livers of F344 rats following oral treatment with kava extract. Q. Xia, L. Guo, S. Dial, Q. Li, P -C. Chan, P. P. Fu

42. Analysis of hydroxybenzo[a]pyrenes in urine by liquid chromatography-tandem mass spectroscopy: Applications as a response biomarker for polycyclic aromatic hydrocarbon (PAH) exposure. S. Sen, S. L. Gelhaus, I. A. Blair

43. Analysis of RNA secondary modifications as biomarkers of exposure. C. Chan, K. Taghizadeh, T. Begley, P. Dedon

44. Analysis of the products from the arylation of deoxyguanosine and DNA by phenols under oxidative conditions. A. M. Fleming, X. Xu, A. Kannan, J. G. Muller, C. J. Burrows

45. Arylhydrocarbon receptor (AhR)-dependent DNA strand breaks by Benzo[a]pyrene-7,8-dione, a PAH metabolite of Aldo-Keto Reductase (AKR). J. H. Park, A. J. Frey, T. M. Penning

46. Cellular nucleotide pools as targets for nitrosative deamination during inflammation. V. Dendroulakis, W. M. Deen, P. Dedon

47. Characterization of furan metabolites and their potential role in furan-derived protein binding. D. Lu, M. M. Sullivan, L. A. Peterson

48. Characterization of lipid peroxidation using a novel thiadiazabicyclo endogenous glutathione adduct in a paraquat-induced model of oxidative stress . S. S. Basu, V. V. Shuvaev, V. R. Muzykantov, I. A. Blair

49. CTP-347: A deuterated analog of paroxetine with greatly reduced CYP2D6 mechanism-based inactivation. A. J. Morales, R. Gallegos, A. Jones, V. Uttamsingh, C. Cheng, G. Bridson, J. F. Liu, D. Wells, R. Tung, R. Zelle, S. Harbeson

50. Cu(II)/H₂O₂/Ascorbate-induced Formation and in-vitro Replication of Thymidine Glycol/8-Oxo-2'-deoxyguanosine Tandem Lesions. Y. Jiang, Y. Wang

51. Defining the molecular mechanisms of environmental carcinogens in lung carcinogenesis. S. L. Gelhaus, T. Penning, I. A. Blair

52. Designing compounds capable of forming 3-methyladenine DNA adducts in estrogen receptor positive cells. S. Varadarajan, H. Perry, L. Smith, T. Lynch, S. Miller, B. Kelly

53. Effect of N²-alkylguanine adducts on replication by Y-class Sulfolobus solfataricus DNA polymerase Dpo4. H. Zhang, R. L. Eoff, K. C. Angel, F. P. Guengerich

54. Effects of chemical structure of bulky DNA lesions and base sequence on the removal of DNA damage by nucleotide excision repair mechanisms in vitro. Y. Liu, K. Kropachev, D. Reeves, L. Zhang, J. Ren, M. Kolbanovskiy, N. E. Geacintov

55. Effects of endogenous cytosine methylation on repair of O⁶-Me-dG adducts by O⁶-Alkylguanine DNA alkyltransferase. R. Guza, Q. Fang, A. E. Pegg, N. Tretyakova

56. Exocyclic 2'-deoxyadenosine adducts of 1,3-butadiene: synthesis, structure elucidation, and effects on DNA structure. U. Seneviratne, T. D. Dissanayake, N. Tretyakova

57. Formation of cysteine-tyrosine crosslinks via a sulfenic acid intermediate. A. H. Cummings, K. Keerthi, K. S. Gates

58. Formation of RNA adduct with a novel endogenous mutagen and carcinogen, aminophenylnorharman. Y. Totsuka, T. Takamura-Enya, T. Sugimura, K. Wakabayashi

59. Genotoxicity and mutagenicity of 6-thioguanine and its oxidation/methylation products in vivo. B. Yuan, Y. Wang

60. Human AKRs display quinone reductase activity with PAH quinones and equilenin-o-quinone . C. A. Shultz, J. L. Bolton, R. G. Harvey, T. M. Penning

61. Hydrogen sulfide, an endogenous cellular signaling agent, generates reactive oxygen species under physiologically-relevant conditions. M. A. Hoffman, S. Sivaramakrishnan, K. S. Gates

62. Identification and quantification of 15-oxo-eicosatetraenoic acid, a novel 15-lipoxygenase-derived arachidonic acid metabolite in an atherosclerosis cell model. C. Wei, P. Zhu, S. J. Shah, I. A. Blair

63. Identification and quantification of candidate protein biomarkers of preterm birth by liquid chromatography/tandem mass spectrometry. S. J. Shah, E. Ciccimaro, K. Yu, S. I. Parry, I. A. Blair

64. Identification of Artifacts in Cyanide Trapping of Reactive Intermediates in N-methyl Piperazine Analogs. C. M. Resuello, Z. Minli, C. S. Elmore, M. E. Powell

65. Identification of DODE-modified serum proteins from mouse models of inflammation. M. V. Williams, A. Chiang, J. S. Wishnok, S. R. Tannenbaum

66. Isoprostanes profiling by liquid chromatography electron-capture atmospheric pressure chemical ionization mass spectrometry (LC-ECAPCI/MS). C. Mesaros, S -H. Lee, I. A. Blair

67. Lipid-derived biomarkers of cigarette smoke exposure in exhaled breath condensates. S. H. Bhat, S. L. Galhauz, I. A. Blair

68. Mass spectrometric analysis of histone phosphorylation induced by ionizing radiation and other DNA damaging agents. M. S. DeMott, K. T. Taghizadeh, P. C. Dedon

69. Methylating and carboxymethylating agents from N-nitroso-1,3-oxazolidin-5-one (NOZ-5), a possible product of endogenous nitrosation. R. N. Loeppky, Y. Li, S. Rajagopal

70. N²-(1-Carboxyethyl)deoxyguanosine: Potential mutagenic and prognostic implications of glycated DNA . D. Tamae, J. Termini

71. Oxidative stress mediated DNA damage on exposure of cigarette smoke. D. Mangal, A. Y. Wehr, S. H. Lee, C. Mesaros, T. grosser, S. Fries, T. M. Penning, I. A. Blair

72. Photosensitized oxidative DNA damage followed from hole injection to chemical product formation and strand cleavage. B. H. Yun, Y. A. Lee, A. Kolbanovskiy, P. C. Dedon, N. E. Geacintov, V. Y. Shafirovich

73. Quantification of N6-formyl lysine: A pathological secondary modification of histone proteins. B. Edrissi, B. Pang, K. T. Taghizadeh, P. Dedon

74. Quantification of the spectrum of RNA damage products in a mouse model of inflammation. J. L. McFaline, B. Pang, M. R. Sullivan, E. G. Prestwich, K. T. Taghizadeh, P. Dedon

75. Quantitative NMR metabolic profiling for drug safety assessments. H. Vu, Q. Xu, E. Xu, B. Schaefer

76. Replication of an Oxidized Abasic Site: The Structural Basis for Breaking the A-Rule. H. Huang, M. M. Greenberg

77. Reversibility of covalent electrophile-protein adducts and chemical toxicity. D. Lin, D. C. Liebler

78. Role of aldo-keto reductase (AKR) 1B10 in human lung carcinogenesis. A. M. Quinn, R. G. Harvey, T. M. Penning

79. SILAC based approach for the analysis of quiescent and activated pancreatic stellate cells. A. Y. Wehr, K. H. Yu, I. A. Blair

80. Simultaneous quantitation of cellular cysteine, homsteine, and glutathione by stable isotope dilution LC-MS. S. Khartulyari, C. Wei, A. S. Whitehead, I. A. Blair

81. Site-specific identification of 3-nitrotyrosine in proteins. M. R. Martinez, I. A. Blair, H. Ischiropoulos

82. Structure of a DNA-Peptide Conjugate Arising from the Acrolein-Induced 1,N²-gamma-Hydroxypropano-dG Adduct: Formation of a Carbinolamine Linkage and Minor Groove Orientation of the Peptide. H. Huang, I. D. Kozekov, H. Wang, A. Kozekova, C. J. Rizzo, M. P. Stone

83. Sub-picogram per milliliter determination of the tobacco-specific carcinogen metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) in human urine using liquid chromatography - tandem mass spectrometry: Application to studies of secondhand tobacco smoke exposure. P. Jacob III, C. Havel, D -H. Lee, L. Yu, N. L. Benowitz

84. Systematic study of the potential arylating capabilities of a series of benzoquinones, naphthoquinones, and anthraquinones. R. E. Shaw, P. A. Mazzer, M. D. Backstrom

85. Toxicity study of hydroxyapatite nanomaterials with different shape using osteoblast cell. L. Chen, J. C. -MLee, H. Li

86. Variability in levels of urinary hydroxylated polycyclic aromatic hydrocarbon metabolites. E. N. Porter, Z. Li, L. C. Romanoff, D. A. Trinidad, A. Sjodin

87. Translesion synthesis, blockage, and base sequence context effects with a bulky carcinogen N²-dG adduct: Comparing A- and Y-family DNA polymerases. P. Xu, L. Oum, N. E. Geacintov, S. Broyde

88. Trainable QSAR model of Ames genotoxicity. R. Didziapetris, K. Lanevskij, P. Japertas

Wednesday Morning

Environmental and Human Health Impacts of Nanomaterials

A. B. Kane and R. Hurt, Organizers

8:30 -89. Environmental and human health impacts of nanomaterials. A. B. Kane

8:45 -90. Biological activity of mineral fibers and carbon particulates: Implications for nanoparticle toxicity and the role of surface chemistry. P. K. Dutta

9:30 -91. Cellular and subcellular interactions with nanoparticles. G. Orr

10:15 - Intermission.

10:30 -92. Potential adverse human health impacts of nanomaterials. G. Oberdörster

11:15 -93. Designing nanomaterials for environmental health and safety. R. Hurt

Wednesday Afternoon

General Papers

K. S. Gates, Organizer

1:00 -94. Are we focusing on the right toxicants for assessing the toxicological properties of smokeless tobacco products J. H. Lauterbach

1:15 -95. Characterization of precursors to trihalomethanes formation in the north china source water . Y. Lin, J. Yin

1:30 -96. Computational evaluation of mechanisms for the formation of guanidinohydantoin from spiroiminodihydantoin . B. H. Munk, Y. Ye, C. J. Burrows, H. B. Schlegel

1:45 -97. DNA Adduct formation in F-344 rats treated chronically with the tobacco-specific lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and enantiomers of its metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL). S. S. Hecht, S. Zhang, Y. Lao, P. W. Villalta, P. Upadhyaya

2:00 -98. Efficient and accurate bypass of a minor-groove DNA adduct by DinB DNA polymerase in vitro and in vivo. Y. Wang, B. YUAN, H. Cao, Y. Jiang, J. Wang

2:15 -99. Identification of binding hot spots of cytochrome P450 3A4 by computational solvent mapping. G -Y. Chuang, D. Kozakov, R. Brenke, S. Vajda

2:30 - Intermission.

2:45 -100. Oxidation of DNA by carbonate radical anions in DNA results in the formation of novel intrastrand cross-links. C. Crean, N. E. Geacintov, V. Shafirovich

3:00 -101. Oxidatively generated sugar fragments and DNA adduct formation. A. C. Bryant-Friedrich, A. Boghici

3:15 -102. Spontaneous DNA alkylation with a quinolinyl quinone methide adduct under aqueous conditions. Q. Zhou

3:30 -103. Structural studies of butadiene-derived adducts. W. Xu, S. K. Musser, T. Nielsen, L. V. Nechev, R. P. Hodge, T. M. Harris, C. M. Harris, R. S. Lloyd, M. Egli, M. P. Stone

3:45 -104. Structure of duplex DNA containing (1,N²)-α-OH-PdG, the minor acrolein-derived lesion. T. Zaliznyak, R. R. Bonala, M. Lukin, F. Johnson, C. de los Santos

4:00 -105. Synthesis and characterization of amino acid adducts from the HIV reverse transcriptase inhibitor nevirapine . M. M. Marques, I. Martins, A. M. Antunes, P. P. Santos, G. Gamboa da Costa, F. A. Beland