Annual Meeting Program - Society of Toxicology

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Society of Toxicology 2008 Program Description (Continued) Abstract # #2306 Poster Board Number.......................................533 A CARDIOVASCULAR SAFETY ASSESSMENT PARADIGM FOR THE EARLY IDENTIFICATION OF PROARRHYTHMIC AND TORSADAGENIC COMPOUNDS. C. Frantz 1 , D. Misner 1 , E. Meierhenry 1 , M. Fielden 1 , L. Guo 2 , J. Ly 1 , H. Uppal 1 , D. Rotstein 1 , P. Senese 3 , M. Albassam 3 , M. Gralinski 3 , S. Chanda 1 , S. Platz 1 and K. Kolaja 1 . 1 Toxicology, Roche Palo Alto, Palo Alto, CA, 2 Roche, Nutley, NJ and 3 CorDynamics, Chicago, IL. #2307 Poster Board Number.......................................534 EFFECTS OF INSULIN ON THE QT INTERVAL IN ANESTHETIZED DOGS. H. Goto 1 , T. Senba 1 , E. Hosoki 1 , K. Morishita 1 and L. L. Lanning 2 . 1 Toxicology, Otsuka Pharmaceutical Co., Ltd, Tokushima, Japan and 2 Nonclinical Safety Evaluation, Otsuka Pharmaceutical Development & Commercialization, Inc., Rockville, MD. #2308 Poster Board Number.......................................535 NILOTINIB PRODUCES NO DETECTABLE CARDIOTOXICITY AFTER 39 WEEKS OF ORAL (GAVAGE) ADMINISTRATION TO CYNOMOLGUS MONKEYS. K. Bowenkamp 1 , C. Hayden 1 , G. Argentieri 1 , M. Osier 2 , E. Giddens 2 , P. Savage 1 , H. Smith 1 and P. Sahota 1 . 1 Novartis Pharmaceuticals, East Hanover, NJ and 2 SNBL USA, Everett, WA. #2309 Poster Board Number.......................................536 TOXICOLOGICAL EVALUATION OF BMS-747158, A PET MYOCARDIAL PERFUSION IMAGING AGENT. M. Mistry 1 , D. Onthank 1 , J. Green 1 , S. Cicio 1 , D. Casebier 1 , S. Robinson 1 , R. Kowalski 2 and T. Baird 2 . 1 Bristol- Myers Squibb Medical Imaging, North Billerica, MA and 2 MPI Research, Inc, Mattawan, MI. #2310 Poster Board Number.......................................537 TOXICITY OF NORWALK VLP VACCINE FOLLOWING REPEATED INTRANASAL ADMINISTRATION TO NEW ZEALAND WHITE RABBITS. S. Godin 1 , K. Wheeler 1 , L. Murphy 1 and R. Sublett 2 . 1 Bridge Global Pharmaceutical Services, Inc., Gaithersburg, MD and 2 LigoCyte Pharmaceuticals, Inc., Bozeman, MT. #2311 Poster Board Number.......................................538 DRUG-INDUCED PHOSPHOLIPIDOSIS: RELATIONSHIPS BETWEEN HISTOLOGICAL CHANGE, TISSUE INJURY AND DRUG ACCUMULATION. N. Matsumoto, Y. Takenobu, K. Shimouchi, H. Yanagi, K. Yamada and S. Kim. Ono Pharmaceutical Co., Ltd., Osaka, Japan. #2312 Poster Board Number.......................................539 INCREASED EFFICIENCY OF PROCONVULSANT SCREENING THROUGH STRATEGIC USE OF ELECTROCONVULSANT MODELS. M. Bell, C. S. Lee and R. A. Bialecki. Safety Assessment, AstraZeneca Pharmaceuticals, Wilmington, DE. Sponsor: P. Ciaccio. #2313 Poster Board Number.......................................540 TEMPORAL RELATIONSHIP OF PHOSPHOLIPIDOSIS AND MITOCHONDRIA TOXICITY IN PRIMARY RAT CEREBELLAR CULTURES. L. R. Barone and P. J. Ciaccio. Safety Assessment, AstraZeneca, Wilmington, DE. Abstract # #2314 Poster Board Number.......................................541 14-DAY SODIUM 2, 2-DIMETHYLBUTYRATE (ST-20) NEURO/GENOTOXICITY STUDY IN RATS. M. Hawk 1 , G. Ritchie 1 , M. Ryan 1 , D. Vasconcelos 1 , V. Yildiz 1 , D. Contose 1 , J. D. Johnson 1 , S. Perrine 2 , J. Peggins 3 , J. Tomaszewski 3 and P. Terse 3 . 1 Battelle, Columbus, OH, 2 Boston University School of Medicine, Boston, MA and 3 National Cancer Institute, Bethesda, MD. #2315 Poster Board Number.......................................542 PEDIATRIC NON CLINICAL SAFETY OF LEVETIRACETAM IN COMPARISON TO OTHER AEDS. M. Léonard, S. Dhalluin and G. Rose. Non-Clinical Development, UCB Pharmacology SA, Braine-l’Alleud, Belgium. #2316 Poster Board Number.......................................543 COLLECTION OF CEREBROSPINAL FLUID BY DIRECT PUNCTURE OR BY SURGICALLY IMPLANTED PORTS IN MONKEYS. J. Perron, Y. Trudel, F. Emond, H. Simard, M. Stilianesis and C. Copeman. Toxicology, Charles River Labs, Preclinical Services Montreal Inc., Senneville, QC, Canada. Sponsor: C. Banks. #2317 Poster Board Number.......................................544 A PERFORMANCE STANDARD FOR DEVELOPMENT OF THE MODIFIED IRWIN TEST AS PART OF A NEUROLOGICAL ASSESSMENT AND A FUNCTIONAL OBSERVATIONAL BATTERY (FOB) IN CD-1 MICE. A. Blackburn, S. Authier, M. Legaspi and G. Washer. LAB Research Canada, Laval (Montreal), QC, Canada. #2318 Poster Board Number.......................................545 NEUROBEHAVIORAL EFFECTS OF D-AMPHETAMINE AND CARBARYL IN THE VALIDATION OF SAFETY PHARMACOLOGY CENTRAL NERVOUS SYSTEM TESTING METHODS IN SPRAGUE DAWLEY RATS. S. Bayreuther, S. Wilson, B. Countey, C. Eisenhauer and R. Oates. Preclinical Services, Charles River Laboratories, Shrewsbury, MA. Sponsor: S. Bulera. #2319 Poster Board Number.......................................546 MOTOR ACTIVITY AND FUNCTIONAL OBSERVATIONAL BATTERY IN RATS TREATED WITH EMD 509847 AND CNS REFERENCES. B. C. Gottschling, P. Tempel and F. von Landenberg. Institute of Toxicology, Merck KGaA, Merck Serono, Darmstadt, Germany. #2320 Poster Board Number.......................................547 THE SIGNIFICANCE OF SKIN DISTRIBUTION OF DRUGS FOR THE ELICITATION OF PHOTOTOXIC REACTION. K. Yamada, A. Akimoto, H. Kawashima, N. Matsumoto and S. Kim. Ono Pharmaceutical Co., Ltd, Osaka, Japan. #2321 Poster Board Number.......................................548 IN VITRO ASSAYS FOR EVALUATING THE ULTRAVIOLET A (UV-A) INDUCED DAMAGE IN CULTURED HUMAN RETINAL PIGMENT EPITHELIAL CELLS. L. Lee. Pfizer Global R&D, San Diego, CA. Sponsor: W. Yvonne. Thursday up-to-date information at www.toxicology.org 287
47 th Annual Meeting & ToxExpo Program Description (Continued) Thursday Abstract # Abstract # #2322 Poster Board Number.......................................549 TOXICOLOGY STUDIES TO SUPPORT CLINICAL DEVELOPMENT OF TREMELIMUMAB, A CYTOTOXIC T LYMPHOCYTE-ASSOCIATED ANTIGEN 4 (CTLA4) BLOCKING MONOCLONAL ANTIBODY. G. Finch 1 , D. Hanson 1 , F. Wang 1 , D. Guyot 2 , L. Morton 1 , T. Kawabata 1 , M. Hurtt 1 and J. Gomez-Navarro 1 . 1 Pfizer Global Research and Development, Groton/New London, CT and 2 Amgen, Thousand Oaks, CA. #2323 Poster Board Number.......................................550 CAECINOGENICITY STUDY OF THE NEW PYRAZOLOPYRIMDINONE DERIVATIVE K-1089 FOR ERECTILE DYSFUNCTION IN F344 RATS. S. Cha, H. Lee, M. Park, E. Jeong, K. Lee and S. Han. Korea Institute of Toxicology, Daejeon, South Korea. Sponsor: W. Koh. #2324 Poster Board Number.......................................551 DOES ENVIRONMENTAL ENRICHMENT AFFECT TUMOUR INCIDENCE IN RATS? I. Taylor, L. K. Earl, S. Cook and J. F. Thomas. Huntingdon Life Sciences, Alconbury, United Kingdom. Sponsor: O. Green. #2325 Poster Board Number.......................................552 TUMORS IN RATS ASSOCIATED WITH IMPLANTABLE MICROCHIP IDENTIFICATION DEVICES. B. S. Wahle 1 , L. E. Elcock 2 , S. G. Lake 1 , B. P. Stuart 1 and L. P. Sheets 1 . 1 Toxicology, Bayer CropScience LP, Stilwell, KS and 2 Pathology Associates, Inc., Kansas City, MO. #2326 Poster Board Number.......................................553 SPONTANEOUS HIBERNOMAS IN SPRAGUE-DAWLEY RATS. R. H. Bruner 2 , G. A. Parker 2 , M. N. Novilla 2 , C. A. Picut 2 , J. B. Kirkpatrick 1 and T. P. O’Neill 1 . 1 Pathology, WIL Research Laboratories, Ashland, OH and 2 Pathology, Biotechnics, Hillsborough, NC. Thursday Morning, March 20 9:00 AM to 11:45 AM Room 615 Oxidative Signaling and Redox Biology SYMPOSIUM SESSION: CELLULAR REDOX STATUS AND ZINC SIGNALING Chairperson(s): Y. James Kang, University of Louisville, Louisville, KY and Dean Jones, Emory University, Atlanta, GA. Endorsed by: Mechanisms Specialty Section* Metals Specialty Section Molecular Biology Specialty Section Cellular redox status constantly changes under both physiological and stress conditions. The redox change modifies cellular signaling system, leading to functional adaptation to the physiological demand or the stress imposition. Zinc/cysteine coordination in proteins is sensitive to redox changes and is therefore used in redox switches. There are two major classes of redox zinc switches: the first are redox sensors that undergo conformational changes through zinc release to alter their functions, although the released zinc may not have known functions. The second are redox transducers that release zinc for the purpose of changing the function of other proteins through the released zinc. The function of the redox transducers thus is to convert the redox signal to zinc signals. There is virtually no free zinc in the cell under physiological conditions and zinc availability is tightly controlled through uptake, intracellular sequestration, and controlled trafficking. Metallothionein (MT), as a redox transducer, plays a critical role in the redox sensing and zinc signaling. Oxidation of the sulfur ligands in MT mobilizes zinc, while reduction of the oxidized ligands enhances zinc binding. This MT redox cycle provides an excellent control mechanism for the availability of intracellular zinc. Many zinc proteins are activated or inactivated after receiving zinc under oxidative stress conditions. These zinc proteins are the effectors of zinc signaling and involved in signal transduction, energy metabolism, mitochondrial function, and gene expression. This symposium will present discussions on (1) cellular redox responses under physiological and stress conditions; (2) zinc transporters and the regulation of zinc intracellular movement in mammalian systems; (3) zinc/cysteine coordination in proteins as a sensor to redox signaling and the converting of redox signaling to zinc signaling though MT redox cycle; and (4) regulation of gene expression by zinc-finger transcription factor. #2327 9:00 CELLULAR REDOX STATUS AND ZINC SINGALING. Y. Kang. Medicine, University of Louisville School of Medicine, Louisville, KY. #2328 9:05 REDOX REGULATION OF CELL SIGNAL TRANSDUCTION. D. P. Jones. Medicine, Emory University, Atlanta, GA. #2329 9:45 ZINC TRANSPORTERS AND THE REGULATION OF INTRACELLULAR ZINC TRAFFICKING. D. Eide. Nutritional Sciences, University of Wisconsin-Madison, Madison, WI. Sponsor: J. Kang. #2330 10:25 METALLOTHIONEIN REDOX CYCLE AND ZINC SIGNALING. Y. Kang. Medicine, University of Louisville School of Medicine, Louisville, KY. #2331 11:05 REGULATION OF METAL-INDUCIBLE TRANSCRIPTION BY A ZINC-FINGER TRANSCRIPTION FACTOR. J. H. Freedman 1 , E. K. Braithwaite 1 and Y. Jin 2 . 1 LMT, NIEHS, NIH, DHHS, Research Triangle Park, NC and 2 Duke University, Durham, NC. Thursday Morning, March 20 9:00 AM to 11:45 AM Room 605 Developmental Basis of Disease SYMPOSIUM SESSION: PERINATAL EXPOSURE TO NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS (NRTIS) INDUCES TRANSPLACENTAL GENOTOXICITY AND MITOCHONDRIAL TOXICITY Chairperson(s): Barbara Shane, NIEHS, Research Triangle Park, NC and Miriam Poirier, National Institutes of Health, Bethesda, MD. Endorsed by: Carcinogenesis Specialty Section* Highly active antiretroviral therapy (HAART), containing two NRTIs, has been remarkably beneficial in managing HIV-1 infection and AIDS. However, increasing evidence suggests that in some HIV-1-uninfected children born to HIV-1-infected mothers, perinatal NRTI exposure may have long-term genotoxic and mitochondrial consequences. Recent studies, compiled in a special issue of Environmental and Molecular Mutagenesis (Vol. 48, April/May 2007), support earlier conclusions that AZT is a transplacental carcinogen in mice, becomes incorporated into DNA of fetal mice, humans and monkeys, and induces mutagenesis (including p53 transversion mutations) and micronuclei in mice and humans exposed to NRTIs in utero. Currently evidence for increased malignancy in HIV-1-uninfected children born to HIV-1-infected mothers who received NRTI therapy during pregnancy is lacking, but widespread use of NRTIs in human pregnancy has been recommended only since 1994. An additonal area of concern is mitochondrial compromise, which occurs in infants exposed to NRITs in utero 288 SOT’s 47 th Annual Meeting
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