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704 IDENTIFICATION OF A MOUSE NOVEL GENE THAT WAS INDUCED UPON GENOTOXIC STRESS AND POTENTIALLY INVOLVED IN DNA DAMAGE RESPONSE OR REPAIR. Y. Wu 1 , Y. Luan 1 , X. Qi 1 , T. Suzuki 2 and J. Ren 1 . 1 Center for Drug Safety Evaluation and Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China and 2 Division of Cellular and Gene Therapy Products, National Institute of Health Sciences, Tokyo, Japan. Identifying genotoxic stress responsive genes and using these genes as molecular biomarker is one of prospective approaches for genotoxicity assessment. In our previous microarray study performed in mice administrated with 7 genotoxic chemicals and 4 non-genotoxic chemicals, we identified a novel gene named as BC, whose expression was specifically up-regulated by most genotoxic chemicals, while remained nearly unchanged upon non-genotoxic chemicals. Some microarray data related to BC expression was further confirmed by Real-Time PCR. Our research aimed to examine the relationship between BC expression and genotoxic stress, elucidate molecular characteristics of BC and uncover its cellular function. Multiple genotoxic agents, such as methyl methanesulfonate (MMS), etoposide and γ-ray up-regulated BC mRNA expression in NIH/3T3 cells. Expression of BC induced by MMS was in a does-dependent manner and well paralleled with micronucleus formation. Time-course analysis indicated that BC began to be induced at 2 hr, peaked at 4 hr and backed to normal level at 8 hr after 8Gy γ-ray irradiation. Northern-blot and RACE (Rapid Amplification of cDNA Ends) results showed that BC gene had three main transcripts (approximate 2.7, 2.8 and 5.5 kb) consistent with the information in GenBank. Expression of BC could be detected in multiple mouse tissues including heart, liver, spleen, lung, kidney, testis and brain by Real-time PCR. Suppression of BC in NIH/3T3 cells by RNA interference resulted in more severe DNA damage and chromosome damage, as shown by alkaline comet assay and micronucleus test, after γ-ray irradiation. Taken together, we identified a DNA damage response related novel gene (BC) which was induced upon genotoxic-stress, and could be a potential biomarker for genotoxicity. 705 EFFECT OF DEFICIENT BASE EXCISION REPAIR (BER) STATUS ON METHYLMERCURY (MeHg)-INITIATED TOXICITY IN VITRO. S. L. Ondovcik 1 , G. P. McCallum 1 and P. G. Wells 1, 2 . 1 Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada and 2 Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada. Dietary MeHg exposure can damage the adult and fetal central nervous system, potentially in part through production of reactive oxygen species (ROS) and oxidative DNA damage. To assess the roles of ROS and oxidative DNA damage, and the protective role of DNA repair, we used mouse embryonic fibroblasts (MEFs) from wild-type (WT) and oxoguanine glycosylase 1 (Ogg1) knockout (KO) mice, the latter deficient in repair of the oxidative lesion 8-oxo-2’-deoxyguanosine (8-oxodG). Following 6-hr incubation with 0-10 μM MeHg, a concentration-dependent decrease in cell viability was observed in all cells, with the Ogg1 KO MEFs appearing less viable at all concentrations compared to the WTs. This decrease in viability was not reduced by a 30-min preincubation with the free radical spin trapping agent α- phenyl-N-tert-butylnitrone (PBN) (0.1 mM) or its 0.1% dimethyl sulfoxide (DMSO) vehicle. Ongoing studies are evaluating higher PBN concentrations. Sixhr exposure to 6 or 10 μM MeHg enhanced ROS production in both Ogg1 WT and KO MEFs, as measured by the fluorescent probe 5-(and-6)-chloromethyl- 2’,7’-dichlorodihydrofluorescein diacetate acetyl ester (CM-H 2 DCFDA). MeHg enhanced ROS formation in Ogg1 KO MEFs compared to WTs, and PBN preincubation reduced ROS formation in the Ogg1 KO MEFs exposed to 10 μM MeHg. Oxidative DNA damage in Ogg1 KO MEFs was assessed by the level of 8-oxodG normalized for total dG content, determined by high-performance liquid chromatography with electrochemical and UV detection respectively. Preliminary results showed a trend toward a concentration-dependent elevation in 8-oxodG levels following 6-hr incubation with MeHg. Thus, MeHg-initiated ROS may partially contribute, directly or indirectly, to the mechanism of toxicity, while DNA repair status may constitute an important risk factor for environmentally-induced oxidative DNA damage and its pathological consequences. (Support: CIHR, CIHR Frederick Banting and Charles Best Canada Graduate Scholarship [SLO]) 706 CHARACTERIZATION OF POLY(ADP- RIBOSE)POLYMERASE-1 KINETICS AND INHIBITION BY ARSENITE: AN IN VIVO STUDY. B. S. King, K. L. Cooper and L. G. Hudson. Pharmaceutical Sciences, University of New Mexico, Albuquerque, NM. Skin is a target tissue for arsenic carcinogenesis. Low arsenic concentrations enhance DNA damage and skin tumors in mice following ultraviolet radiation (UVR) exposure, but, the underlying mechanisms are unclear. Inhibition of DNA repair enzymes such as Poly(ADP-ribose)polymerase-1(PARP-1) by arsenic are under investigation, yet little is known about PARP-1 activation by UVR in the skin. The initial goal was to characterize the in vivo kinetics of PARP-1 activation following UVR. Skh-1 (hairless) mice were exposed to a single dose of solar simulated UVR (28 kJ/m 2 ). Skin samples were collected post exposure as well as from control animals and analyzed for poly(ADP-ribose) [PAR], a branched polymer attached to acceptor proteins by PARP-1, using immunohostochemistry. PARP-1 activation was found to be rapid and did not persist more than 4-6 hours post exposure. Using the same experimental design, the next objective was to observe PARP-1 inhibition by arsenite in vivo. Skh-1 mice were exposed to 5 mg/L sodium arsenite or non-treated water for 28 days then exposed to a single dose (28 kJ/m 2 ) of solar simulated UVR. As above, skin samples were collected post exposure and analyzed for PAR. Reduced PAR levels were detected in arsenite treated animals as compared to controls indicating inhibition of PARP-1 activity by arsenite. These results show that in vitro observations are retained in an in vivo setting and help to further the knowledge surrounding interactions of arsenic and ultraviolet radiation in skin. This work was supported by NIH award R01 ES015826. 707 IDENTIFYING GENOTOXIC COMPOUNDS USING A BATTERY OF ISOGENIC DNA REPAIR DEFICIENT DT40 CELL LINES IN A QUANTITATIVE HIGH- THROUGHPUT SCREENING (QHTS) PLATFORM. K. Nakamura 1, 4 , S. Sakamuru 2 , R. Huang 2 , K. Witt 3 , C. P. Austin 2 , Y. Taniguchi 1 , K. Kono 4 , R. R. Tice 3 , S. Takeda 1 and M. Xia 2 . 1 Radiation Genetics, Graduate School of Medicine, Kyoto University, Kyoto, Japan, 2 NIH Chemical Genomics Center, Bethesda, MD, 3 National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC and 4 Hygiene and Public Health, Graduate School of Medicine, Osaka Medical College, Osaka, Japan. DNA repair pathways play a critical role in cellular homeostasis by repairing DNA damage induced by endogenous processes and xenobiotics. Isogenic chicken DT40 cell lines deficient in different DNA repair pathways can be used to identify genotoxic compounds and aid in characterizing the nature of the DNA damage induced(1). As part of the U.S. Tox21 program, we evaluated the ability of seven isogenic DNA repair deficient DT40 cell lines to identify direct-acting genotoxic chemicals within an NTP 1408 compound library. Evaluation was based on increased cytotoxicity in one or more of the cell lines deficient in a DNA repair pathway (e.g., pol β, ku70/rad54, ubc13, rev3, fanc) compared with the wild-type cell line. The assays were optimized for qHTS in a 1536-well plate format. We identified several well-known genotoxic compounds (e.g., melphalan, adriamycin) as well as other compounds that induced differential cytotoxicity in one or more DNA repair deficient cell lines. Active compounds were evaluated further by comparing the frequency of induced chromosomal damage in the appropriate DNA repair deficient cell lines and the wild-type cell line. Our results demonstrate the utility of this approach for screening large compound libraries for genotoxic activity using 1536- well based qHTS and for acquiring detailed information on the type(s) of DNA damage induced by these compounds. Supported by NIEHS Interagency Agreement Y2-ES-7020-01. (1)Ji et al. doi:10.1289/ehp.0900842 708 METHANOL EXPOSURE DOES NOT LEAD TO ACCUMULATION OF OXIDATIVE DNA DAMAGE IN MICE, RABBITS, OR PRIMATES. G. P. McCallum 1 , M. Sui 1 , S. L. Ondovcik 1 and P. G. Wells 1, 2 . 1 Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada and 2 Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada. In vitro and in vivo genotoxicity tests with methanol (MeOH) indicate that it is not a mutagen, but controversy exists regarding the carcinogenic potential of this agent due to conflicting reports in long-term rodent cancer bioassays. One potential mechanism whereby MeOH could indirectly damage DNA is via free radical-initiated, reactive oxygen species (ROS)-mediated oxidative DNA damage. To investigate this possibility we treated male CD-1 mice, New Zealand white rabbits, and cynomolgus monkeys with MeOH (2.0 g/kg ip) and at 6 hr assessed tissue oxidative DNA damage, measured as 8-oxo-2’-deoxyguanosine (8-oxodG) by HPLC with electrochemical detection. We found no MeOH-dependent increases in 8- 150 SOT 2010 ANNUAL MEETING
oxodG in bone marrow, spleen, kidney, lung or liver of any species. Chronic treatment of CD-1 mice with MeOH (2.0 g/kg ip) daily for 15 days also did not increase 8-oxodG levels in these organs. Further studies in DNA repair-deficient oxoguanine glycosylase 1 (Ogg1) knockout (KO) mice support these findings. Fibroblasts from Ogg1 KO mice accumulated 8-oxodG at 6 hr following acute exposure to the ROS-initiating renal carcinogen potassium bromate (KBrO 3 ; 2.0 mM), but did not accumulate 8-oxodG following exposure to 125 mM MeOH. In vivo exposure of Ogg1 KO mice to KBrO 3 (100 mg/kg ip) doubled renal 8-oxodG levels 24 hr post-dose. In contrast, MeOH (2.0 g/kg ip) did not alter renal levels of 8-oxodG at 6 or 24 hr post-dose in Ogg1 KO mice. Taken together these observations suggest that MeOH exposure does not promote the accumulation of oxidative DNA damage, and that it is unlikely that environmental exposure to MeOH would lead to carcinogenesis via this mechanism. (Support: Methanol Foundation, CIHR, CIHR Rx&D postdoctoral award [GPM], CIHR Frederick Banting and Charles Best doctoral award [SLO]) 709 POTENT INHIBITION OF PEROXYNITRITE-INDUCED DNA STRAND BREAKAGE AND HYDROXYL RADICAL FORMATION BY THE COMMONLY USED DRUG VEHICLE DMSO AT EXTREMELY LOW CONCENTRATIONS. Z. Jia, H. Zhu, Y. Li and H. P. Misra. Edward via Virginia College of Osteopathic Medicine, Virginia Tech Corporate Research Center, Blacksburg, VA. Dimethyl sulfoxide (DMSO) is frequently used as a solvent for many water-insoluble drugs in biological studies at concentrations often up to 1%. However, little is known about its effects on oxidative DNA damage at very low concentrations (0.005-0.5%). This study was undertaken to investigate the effects of DMSO on peroxynitrite-induced DNA strand breaks, a critical event leading to peroxynitriteelicited cytotoxicity. Incubation of φX-174 plasmid DNA, with 3-morpholinosydnonimine (SIN-1), a peroxynitrite generator, led to the formation of DNA strand breaks in a concentration and time-dependent fashion. The presence of DMSO at concentrations of 0.005-0.5% was found to significantly inhibit SIN-1-induced DNA strand breaks in a concentration-dependent manner. However, DMSO at the above concentrations showed no affect on SIN-1-mediated oxygen consumption, indicating that DMSO did not affect the auto-oxidation of SIN-1 to form peroxynitrite. It is observed that incubation of the plasmid DNA with authentic peroxynitrite resulted in significant formation of DNA strand breaks, which could also be dramatically inhibited by the presence of DMSO at 0.005-0.5%. EPR spectroscopy, using 5,5-dimethylpyrroline-N-oxide (DMPO) as a spin trap demonstrated the formation of DMPO-hydroxyl radical adduct (DMPO-OH) from the SIN-1 and authentic peroxynitrite. DMSO at the concentrations ranging from 0.01% to 0.5% significantly inhibited the adduct signal. Taken together, these studies demonstrate, for the first time, that DMSO at extremely low concentrations (0.005-0.5%) can potently inhibit peroxynitrite-mediated DNA strand breakage and hydroxyl radical formation. The results of this study suggest that, where DMSO is applied as a solvent, caution should be observed when evaluating the actions of drugs in experiments involving DNA damage. 710 IDENTIFICATION OF A NOVEL ROLE FOR THE RNA SURVEILLANCE PROTEIN, UPF1, IN OXIDATIVE STRESS INDUCED P53 ACTIVATION. J. S. Gewandter 1 and M. A. O’Reilly 2 . 1 Biochemistry and Biophysics, University of Rochester, Rochester, NY and 2 Pediatrics, University of Rochester, Rochester, NY. Sponsor: B. Lew. Genotoxic stress is known to activate the phosphatidylinositol-3-kinase-like kinases (PIKKs); ATM, ATR, and SMG1 to phosphorylate the tumor suppressor protein p53, a protein central to coordination of cell cycle arrest and apoptosis. In addition to its role in monitoring DNA damage, SMG1 plays an important role in the RNA surveillance pathway nonsense mediated mRNA decay (NMD). During NMD SMG1 phosphorylates Upf1, leading to the recruitment of decay proteins to eliminate mispliced RNAs. Using hyperoxia as a model to induce chronic oxidative stress and DNA damage, we now show that Upf1 is also necessary for full activation of p53, suggesting further interplay between RNA and DNA surveillance pathways. SiRNA knock down of Upf1 protein before exposure to hyperoxia decreased the phosphorylation and accumulation of p53 in three independent cell lines. Upf1 mediated changes were post-translational and not involving mdm2, a master negative regulator of p53. Although Upf1 knock down has previously been shown to stall cell cycle, which could indirectly affect p53 activation, loss of Upf1 did not prevent cell cycle progression. Our studies suggest two possible mechanisms. Upf1 could be involved in response to both damaged DNA as a mediator of p53 activation and RNA in NMD. On the contrary, damaged RNA could activate pathways that up until this point have been thought to respond wholly to DNA damage, and this could be mediated through Upf1. 711 EXPLORING MECHANISMS OF INFLAMMATION- ASSOCIATED SYSTEMIC GENOTOXICITY. A. M. Westbrook 1 , B. Wei 2 , J. Braun 2 and R. H. Schiestl 2, 1 . 1 Molecular Toxicology Interdepartmental Program, UCLA, Los Angeles, CA and 2 Department of Pathology and Laboratory Medicine, UCLA, Los Angeles, CA. We have previously demonstrated acute and chronic intestinal inflammation characteristic to inflammatory bowel disease patients induces genotoxicity not only locally in the colon, but also systemically in the peripheral blood, utilizing several mouse models of intestinal inflammation. We believe this may be a mechanism for inflammation-associated carcinogenesis for cancers arising outside the site of inflammation, such as lymphoma. In order to further characterize the resultant systemic genotoxicity and explore causative mechanisms, we identified and characterized genotoxicity in other cell types and subpopulations of cells, measured correlation of disease activity to the observed genotoxicity, and determined the role of cytokines in inducing systemic genotoxicity. Utilizing the alkaline comet assay and γH2AX immunostaining, DNA damage was highest in CD4 and CD8 T cells versus other cell types in the peripheral blood, and also detected in the spleen, mesenteric lymph nodes, peripheral lymph nodes, and in the intestinal epithelial cells. Levels of DNA damage also correlated to severity of clinical inflammation, in dextran sodium sulfate treated mice and in IL-10 deficient mice. Injection of the cytokine TNF-α into wild type mice was sufficient to induce genotoxicity, and levels of DNA damage were sustained for longer period of time when combined with injection with IL-1β. In conclusion, systemic DNA damage is characteristic to multiple organs and cell types, correlates to disease activity, and TNF-α is sufficient to induce the observed inflammation-associated systemic genotoxicity. 712 DOUBLE STRAND BREAK REPAIR IN HUMAN MITOCHONDRIAL EXTRACTS. S. Hunter 1 , J. Meyer 1 and B. Van Houten 2 . 1 Duke University, Durham, NC and 2 University of Pittsburgh, Pittsburgh, PA. Mitochondrial DNA (mtDNA) is prone to double strand breaks (DSBs); however the nature of its repair in human cells is not understood. DSB repair was assayed in highly purified human mitoplasts using a newly developed quantitative PCR-based assay that measures ligation across a restriction site. Using this assay, we demonstrate DSB repair carried out by mitochondrial protein extracts consisting of only mitochondrial matrix proteins. DNA containing 5’ or 3’ overhangs is repaired more efficiently than blunt-ended DNA (13%, 8% and 3% repaired, respectively). Further investigation of the rejoining of PstI-generated DSBs revealed appreciable DNA processing, resulting in the loss of approximately 50 bases surrounding the PstI site. Sequence analysis of over 100 ligation products revealed several patterns of repaired DNA, most with deletions spanning 4-7 bp direct repeats. Results indicate that broken DNA is resected to reveal regions of microhomology, thus allowing annealing and ligation; producing DSB repair-mediated DNA deletions. These observed deletions are strikingly similar to those seen in patients of mitochondrial disorders such as progressive external ophthalmoplegia, Kearns-Sayre syndrome and Pearson Syndrome. We have determined that the exonuclease function of DNA polymerase gamma mediates the 3’ to 5’ resection and is required for the efficient repair of DSBs. Additionally, we hypothesize that the 5’ to 3’ exonuclease responsible for the resection is hSNM1B. hSNM1B has a predicted mitochondrial targeting sequence with a putative cleavage site of 70 amino acids. Using immunofluorescence, hSNM1B-GFP is shown to be targeted to mitochondria. Furthermore, the hSNM1B mitochondrial targeting sequence is both necessary and sufficient for mitochondrial localization. Studies are underway to determine the precise role of hSNM1B in mitochondrial DSB repair. The study of mtDNA DSB repair will help clarify the underlying mechanisms of the aforementioned diseases involving mtDNA deletions between direct repeats that may be associated with DSB repair. 713 DIFFERENCE OF ACRYLAMIDE INDUCING GENOTOXICITY AND ADDUCT FORMATION BETWEEN CHILD AND ADULT RATS. M. Honma 1 , N. Koyama 1, 2 , M. Yasui 1 , S. Takami 1 , M. Takahashi 1 , K. Inoue 1 , M. Yoshida 1 , K. Masumura 1 , T. Nohmi 1 , S. Masuda 2 , N. Kinae 2 , T. Suzuki 3 , T. Matsuda 3 , M. Shibutani 4 and T. Imai 5 . 1 National Institute of Health Sciences, Tokyo, Japan, 2 University of Shizuoka, Shizuoka, Japan, 3 Kyoto University, Kyoto, Japan, 4 Tokyo University of Agriculture and Technology, Tokyo, Japan and 5 National Cancer Center, Tokyo, Japan. The recent discovery of acrylamide (AA), a potent carcinogen in the frying or baking of variety of foods, raises human health concerns, in particular, for children, because AA is relatively highly contained in snacks, cereals, and baby foods. To elucidate the difference genotoxicity of AA to children and adult animals, we treated SOT 2010 ANNUAL MEETING 151
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The Toxicologist Supplement to Toxi
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The Toxicologist Supplement to Toxi
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1 BIOLOGICAL PATHWAY ANALYSIS: AN I
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11 ICH INITIATIVES FOR CONDUCTING P
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models. Experimental approaches and
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30 SILICA AND ASBESTOS IMMUNOTOXICI
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40 NONCANCER TOXICITY POTENTIAL AT
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ased products for patient administr
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nase regulates Hsp27-induced reorga
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exposure resulted in splenomegaly.
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We investigated the effect of imati
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well plate prevented free cell move
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98 DERIVING SIGNATURES OF IN VIVO T
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sulfate, cinnamic aldehyde, 2,4-din
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The final product will be a system
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mercially available STP brands by m
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for six weeks, with 10 mg/kg azoxym
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eceived RES post-TCDD exposure when
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morigenesis. Knocking down of JARID
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163 MICROPET IMAGING OF [18F]-DFNSH
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These results are comparable to tha
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activity as assessed by lever press
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for measured physico-chemical param
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199 DEVELOPMENT OF A MULTIPARAMETER
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To cause PLD, a drug needs to enter
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In contrast to the parent PBDEs and
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transiently transfected HEK 293 cel
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TCDD exposure, 24 h prior to a 20 %
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244 NON-ADDITIVE EFFECTS OF PCB153
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253 COMPARISON OF MIXTURE TOXICITY
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two cerium oxide nanoparticles of v
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271 SIZE-DEPENDENT EFFECTS OF TUNGS
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adigms such as Tox 21 and Toxcast,
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QDs with emission maximum at 800nm
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Cleveland, while others were found
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without the need of animal testing.
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Conclusions: These results are cons
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ing oxime reactivation and organoph
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335 A NON-OXIME IMPROVES SURVIVAL I
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alties suffer from permanent lung i
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ies have established inflammatory b
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363 GENETIC VARIATION IN ISOGENIC M
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372 EVALUATING THE BIOLOGICAL INTER
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dose of 1/20 LD50 (400 mg/kg.bwt) f
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median CR-adjusted isoflavone conce
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data indicate that AhR deletion pro
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February 2006). The rabbit is one o
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tal neurotoxicity (DNT) test (OECD
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of selected microorganisms that are
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BVI. Histopathological analysis was
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446 MOLECULAR CLONING AND CHARACTER
Page 103 and 104: portant in predicting risk. CYPs 1A
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Page 107 and 108: 473 BOVINE CORNEAL OPACITY AND PERM
Page 109 and 110: 482 TYPE III DEIODINASE (D3) IS PRO
Page 111 and 112: tancy evaluation and ranking of bat
Page 113 and 114: 501 CHARACTERIZATION OF ESTERASE, G
Page 115 and 116: 510 REDOX CYCLING BY ENDOGENOUS 2-
Page 117 and 118: prostate cancer cells. All 8 BEL de
Page 119 and 120: metallic nickel nanoparticles. Acti
Page 121 and 122: variety of more or less reactive ch
Page 123 and 124: 550 QUALIFICATION STRATEGIES-GENOTO
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Page 127 and 128: 572 LOW-CHRONIC ARSENIC EXPOSURE: E
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Page 137 and 138: 620 CHARACTERIZATION OF POTENTIAL I
Page 139 and 140: ways. Moreover, both MAP kinase and
Page 141 and 142: 641 POPS IN THE U.S. POPULATION AND
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Page 159 and 160: ment were 18.0 and 4.5 nM for BEAS-
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vasive method for assessing several
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950 ARSENITE DOWN-REGULATES THE CAR
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inflammatory signaling is altered b
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treated wood. Seventy-five of 132 w
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ergy homeostasis and raising levels
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treated with mercury and then with
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997 IN VIVO CORRELATES OF THE MANGA
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of the panel. The panel was compris
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sponse, location, and severity scor
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tant source of n-3 fatty acids such
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old for serious, irreversible or es
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1045 SUBCHRONIC TOXICITY EVALUATION
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sites collected 3 days after inject
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1063 MOLECULAR MECHANISM OF OLANZAP
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esponses, and can be available for
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hence more physiologically relevant
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thesized apoproteins, so we tested
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vate CYP3A5 but could be released b
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1108 STYRENE-INDUCED TOXIC EFFECTS
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1118 THE PRESENCE OF DIETHYL FUMARA
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zebrafish cells were first exposed
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utene-1,4-dial, which has been show
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groups, largely due to lower non-HD
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Exposure to gluten in individuals w
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contrast to VGSC activators such as
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1175 70% HYDROFLUORIC ACID (HF) CUT
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axis. An increase in hyaline drople
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1194 esiRNA AND siRNA HIGH-THROUGHP
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1203 ARYL HYDROCARBON RECEPTOR-DNA
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permeability (calcein), mitochondri
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olytic caspase activation, caspase-
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teristics of a human T-type voltage
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80% of the activity from the yellow
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1251 DEVELOPMENTAL EXPOSURE TO DELT
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1260 MANEB ENHANCES MPP + -INDUCED
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demonstrated by knockdown of beclin
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1278 PINK1 AND MITOCHONDRIAL DYNAMI
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treatment for number of live worms.
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1297 INVESTIGATION OF THE NEUROTOXI
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1306 DEVELOPMENT OF AN IN VITRO ASS
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1315 EVALUATION OF 3- AND 1-METHYLH
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prior to kainic acid-induced seizur
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1334 AFFECT OF GENETIC VARIATION ON
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1346 THE OTHER WORLD OF THE TRANSCR
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strate, leading to excess microvesi
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1368 OVERVIEW OF THERAPEUTIC VACCIN
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to a bovine adrenal cortical epithe
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DOTC had no effects. These results
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1398 PULMONARY TOXICITY OF CERIUM D
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PPARα, LXR, ER, AR and AhR activit
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1417 MECHANISM OF GENDER-DIVERGENT
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els, they disrupt homeostatic contr
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were to characterize exposure of th
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1448 ADVERSE OUTCOME PATHWAYS AND E
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the level in urine was 25% of the m
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1;akt-2 double mutant and pdk-1 mut
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jury effects when compared to contr
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tude than equivalent oral doses. Af
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cells; and increased iNOS and MCP-1
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B6.Cg-Kit W-sh mice. These findings
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1511 STATIN-TREATMENT EFFECTIVELY R
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1520 EFFECT OF INHALATION EXPOSURE
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numbers of IFN-γ producing cells w
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These data indicate that TCDD treat
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esponse to allogenic cells, where P
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larly suppressed LPS-induced TNF-α
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1565 INFLUENCE OF EXPOSURE ROUTE AN
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veloping animals to adverse effects
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the observed CL values were 0.07 L/
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which is most relevant for potentia
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tive impairment, suggesting that ox
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1611 AN IN VITRO METABOLOMICS APPRO
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Expression of the β6 integrin (Itg
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ats (10 μg/kg TCDD). Here we repor
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at liver slices and how the metabon
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with gender differences in AUC and
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oxetine (30 mg/kg reduced to 15 mg/
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eleased from necrotic cells where i
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plants, they are present in surface
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ferentiation (quantitative in-cell
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control for macrophage activation).
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to 0.5μg/ml. Minimal inhibitory co
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lines tested. Given that dex and AT
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tion in the absence of an immune re
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treated rats had lower calcium load
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1740 PROFILING COMPOUNDS WITH CARDI
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dothelial cells confirmed caveolin-
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1758 GINKGO BILOBA EXTRACT INDUCES
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arin-induced suppression of MDR1 ex
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1780 ANTIANDROGENIC AND ANTIPROLIFE
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included in the evaluation, most of
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1799 GUIDANCE ON THE APPLICATION OF
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However, substances with EC3 values
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1816 CD-INDUCED EGFR TRANSACTIVATIO
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1826 KERATIN 7 EXPRESSION IN INDEPE
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centa were collected at the time of
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1845 SYSTEMATIC SCREENING OF YEAST
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underlying the development of co-mo
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eing measured in experimental roden
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ufactured in the US for more than 3
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nine (N7-THB-Gua) and N7-hydroxyphe
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1892 EFFECT OF LAMBDA-CYHALOTHRIN O
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22 in Phase I. Antimicrobial pestic
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kinetic and dynamic differences, an
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iphenyl, saccharin and melamine was
Page 415 and 416:
1930 DEVELOPMENT OF A RELATIVE SOUR
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1939 MODE OF ACTION FOR THE CANCER
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human was about 1.5-fold lower (60
Page 421 and 422:
Disruption of BDEC integrity in alp
Page 423 and 424:
1968 A HUMAN HEPG2 LUCIFERASE ASSAY
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in the offspring during tumor devel
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een developed to investigate perfus
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to 131.73 μg/mL for KLH-specific I
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cell lines (ATCC) were cultured in
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flammation and xenobiotic metabolis
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vide many contributions: with its g
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to-metal joint replacement. For exa
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to be addressed or negotiated. Deci
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especially with anti-TNF therapies.
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genic line Tg(are:eGFP) was created
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2074 COMPUTATIONAL ASSESSMENT OF TH
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2084 INHIBITION OF 11β-HSD1 DECREA
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(T) and express several enzymes inv
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2101 GENISTEIN MODULATION OF BLOOD
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males per group were dosed orally o
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ate the feasibility of assessing re
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changed. Hepatic protein carbonyl l
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sought to examine alterations in he
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2147 A SINGLE AMINO ACID CONTROLS T
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Gstm7) was independent of both CAR
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ility of tungsten trioxide (WO3), t
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ured by real-time PCR array and rel
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glucose, and creatinine levels, and
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Several studies have reported suppr
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exposure between TCDD-exposed labor
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Furthermore, with increasing number
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Society of Toxicology 2010 Author I
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Society of Toxicology 2010 Abstract
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49 th Annual Meeting and ToxExpo A
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The Official Journal of the Society
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