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This work was supported by ROINS039587 1298 TOLUENE EFFECTS ON OXIDATIVE STRESS IN BRAIN REGIONS OF YOUNG-ADULT, MIDDLE-AGE, AND SENESCENT BROWN NORWAY RATS. P. S. Kodavanti, J. E. Royland, J. H. Richards, J. Besas and R. C. MacPhail. NHEERL, U.S. EPA, Research Triangle Park, NC. Aging-related susceptibility to environmental chemicals is poorly understood. Oxidative stress (OS) appears to play an important role in susceptibility and disease in old age. The objectives of this study, therefore, were to test whether OS is a potential toxicity pathway for toluene exposure (a hazardous air pollutant) and to determine if these effects were age-dependent. We examined OS events to delineate reactive oxygen species production [NADPH Quinone oxidoreductase 1 (NQO1), NADH Ubiquinone reductase (UBIQ)], antioxidant homeostasis [total antioxidant substances (TAS) and superoxide dismutase (SOD)], and oxidative damage (total aconitase and protein carbonyls). Male Brown Norway rats (4, 12, and 24 months) were dosed orally with toluene (0, 0.65 or 1 g/kg) in corn oil. Frontal cortex (FC), cerebellum (Cb), striatum (Str), and hippocampus (Hip) were dissected 4 hours after exposure, quick frozen, and stored at 80°C until analysis. Results indicated constitutive age-related changes in some OS parameters in selected brain regions (eg NQO1 increase in Cb and TAS decrease in Str). Toluene effects on several OS endpoints were age- and brain region-specific. For example, toluene exposure increased NQO1 activity in FC and Cb at 4 and 12 months but only in Hip in 24 months. In contrast, toluene decreased TAS levels at 4 months in all brain regions and at 24 months in Cb, but increased TAS levels at 12 and 24 months in FC, Cb, and Hip. Markers of oxidative damage reached significance only at selected ages and/or doses. Aconitase levels were increased at 12 months in FC at 0.65 and 1.0 g/kg, 24 months in FC at 0.65 g/kg, and 24 months in Cb at 1.0 g/kg toluene. Significant increases in protein carbonyl levels in both FC and Cb matched the pattern of aconitase in the FC. These results indicate OS as a potential toxicity pathway, but the complex interaction between age and toluene exposure on OS parameters in different brain regions requires further investigation. (This abstract does not necessarily reflect USEPA policy). 1299 MERCURY-INDUCED PHOSPHATIDIC ACID LIPID SIGNALING IN VASCULAR ENDOTHELIAL CELLS IS REDOX-REGULATED. J. D. Secor 1, 2 , R. B. Patel 1, 2 , S. R. Kotha 1, 2 , R. M. Uppu 3 and N. L. Parinandi 1, 2 . 1 The Ohio State University College of Medicine, Columbus, OH, 2 Pulmonary, Dorothy M. Davis Heart and Lung Research Institute, Columbus, OH and 3 Environmental Toxicology, Southern University and A&M College, Baton Rouge, LA. Mercury has been implicated as a risk factor in cardiovascular diseases. However, the mechanisms of mercury-induced endothelial dysfunction are not known. Earlier, we reported that mercury induces activation of the lipid signaling enzyme, phospholipase D (PLD) in vascular endothelial cells. Here, we hypothesized that vascular endothelial cell PLD would be activated by mercury through the thiolredox regulation. Hence, we used our well-established mouse aortic endothelial cell (MAEC) model and investigated the role of thiol-redox in the methylmercury (MeHg)-induced PLD activation. Our results demonstrated that: (i) MeHg induced PLD activation in dose-and time-dependent manner; (ii) thiol protectants such as N-acetyl-L-cysteine (NAC) and meso-2,3-dimercaptosuccinic acid (DMSA) attenuated MeHg-induced PLD activation; (iii) the novel, PLD-specific inhibitor, 5-fluoro-2-indolyl des-chlorohalopemide (FIPI), completely attenuated the MeHg-induced PLD activation; (iv) the novel thiol-protective compound, N,N’-bis(2-mercaptoethyl)isophtalamdie (BMEI), offered total attenuation of MeHg-induced PLD activation; (v) MeHg caused loss of cellular thiols and increase in ROS production in MAECs. Overall, our study demonstrated that MeHg-induced PLD activation was regulated by the thiol-redox alterations in vascular endothelial cells. Therefore, the PLD-mediated bioactive lipid signaling appears to play a role in the mercury-induced vascular disorders. 1300 GENETIC ABLATION OF IPLA 2 γ INCREASED URINARY MARKERS OF OXIDATIVE STRESS AND INCREASED LIPID PEROXIDATION IN KIDNEY CORTEX OF AGED MICE. A. C. Eaddy, V. M. Kale, J. L. Blakely and R. G. Schnellmann. Pharmaceutical and Biomedical Sciences, Medical University of South Carolina, Charleston, SC. We previously showed that calcium-independent phospholipase A 2 γ (iPLA 2 γ), present in endoplasmic reticulum (ER) and mitochondria, protects renal cells from oxidant injury by preventing and/or repairing oxidant-induced lipid peroxidation. 278 SOT 2011 ANNUAL MEETING Oxidant stress is a major component of age-related deterioration of kidney function and structure, but the role of iPLA 2 γ in this process has not been investigated. Thus, we utilized mice genetically ablated of iPLA 2 γ (KO mice) to investigate its role in age-related oxidant injury and loss of kidney function. Urinary 8-isoprostanes, a biomarker of lipid peroxidation, and 8-hydroxy 2-deoxyguanosine (8- OH dG), a biomarker of oxidative DNA damage, were measured to assess oxidant injury. There were no differences in these markers in male KO and WT mice at 2 months of age. However, 13-month KO mice excreted 9-fold more 8-isoprostanes and 2-fold more 8-OH dG compared to 13-month WT mice. To determine kidney specific oxidant injury, we measured lipid peroxidation (TBARS) in mouse kidney cortex. There were no differences in lipid peroxidation in KO and WT kidney cortex at 2 months of age. However, kidney cortex of 13-month iPLA 2 γ KO mice exhibited 1.7- fold higher TBARS content than 13-month WT controls. To assess kidney function, we measured serum and urine creatinine, urine volume, and urinary NGAL (a marker of acute kidney injury). There were no differences in these parameters between KO and WT mice at 2-months or 13-months of age. In summary, genetic ablation of iPLA 2 γ increased excretion of 8-isoprostanes and 8-OH dG in the urine and increased lipid peroxidation in kidney cortex of male 13month mice. However, at 13-months of age, the level of oxidant injury in the kidney did not result in renal failure. These data support our previous findings that iPLA 2 γ protects renal cells from oxidative stress. This research was supported by F30 ES015964 and DK062028. 1301 FREE FATTY ACIDS SENSITIZE HEPATOCYTES TO ETHANOL METABOLISM-INDUCED DAMAGE. I. Hernandez Resendiz, L. Gomez Quiroz, L. Bucio, V. Souza and C. Gutierrez- Ruiz. Health Sciences, Universidad Autónoma Metropolitana Iztapalapa, Mexico, Mexico. Palmitic (C16:0) and oleic (C18:1) acids are the predominant free fatty acids (FFA) in patients with NAFLD. Accumulation of FFA could induce reactive oxygen species (ROS) production.Hepatocytes have enzymatic, superoxide dismutas (SOD), caltalase (cat) and GSHpx, as and non-enzymatic systems, as gluthatione (GSH), that counteract oxidative stress. GSH is synthesized in two steps catalyzed by γglutamyl cysteine synthetase(γGCS) and GSH synthetase. γGCS is the rate limiting enzyme.Ethanol (EtOH) biotransformation by cytochrome 2E1 (CYP2E1) produces ROS. Delivery of free fatty acids to the liver may render hepatocytes more vulnerable to ethanol metabolism. Objective: to determine if FFA overload in the ethanol metabolizing cell line VL-17A enhance hepatocyte damage due to ethanol metabolism. The hepatic cell line VL-17A, obtained from HepG2 cells transfected with CYP2E1 and alcohol dehydrogenase, was used.Cells were seeded and cultured in presence of 1mM oleic and palmitic acids during 24 h. After that, cells were treated with 100 mM EtOH in presence of FFA for 48 h.Viability was determined by trypan blue assay.Intracellular lipids content were measured with red O oil.CYP2E1, cat, SOD 1 and 2,γGCS and GSHpx were determined by Western blot. VL-17A cells decreased viability 34% with FFA and 43% with FFA plus EtOH after 72 h treatment. Both treatments increased six times intracellular triglyceride content. Treatment with FFA and EtOH increased significantly SOD 1 and 2 and GSHpx compared with FFA treated cells, while no change in cat was found. γGCS decreased 50% and CYP2E1 increased significantly in FFA and EtOH treated cells. EtOH treatment in cells previously treated with FFA decreased viability; increased SOD1 and 2, CYP2E1 content and GSHpx and decreased γGCS. CYP2E1 rise could induce ROS production, and with the decreased cell capacity to produce GSH show that FFA treated cells are more susceptible to the harmful effects of ethanol metabolism. 1302 ALCOHOL-INDUCED BONE LOSS IS BLOCKED IN P47PHOX -/- MICE LACKING FUNCTIONAL NADPH OXIDASES. K. Mercer 2 , R. Wynne 1, 2 , C. Moutos 2 , C. Lumpkin 1 , L. Suva 1 , T. Badger 1, 2 , J. Chen 1, 2 and M. J. Ronis 1, 2 . 1 University of Arkansas for Medical Sciences, Little Rock, AR and 2 Arkansas Children’s Nutrition Center, Little Rock, AR. Chronic ethanol (EtOH) consumption produces bone loss. Previous data suggest a role for NADPH oxidase enzymes (Nox) since the pan-Nox inhibitor diphenylene iodonium (DPI) blocks EtOH-induced bone loss in rats. The current study utilized mice in which Nox enzymes 1,2,3 and 5 are inactivated as a result of knocking out the coactivator protein p47phox. C57BL/6 and p47phox -/-female mice (age 6 wk.) were pair-fed liquid diets of up to 30% EtOH for 4 wk.(blood EtOH 100-200 mg/d). In C57BL/6 mice, EtOH treatment reduced tibial cortical and trabecular bone density (P
mation was decreased to the same level observed in wild type mice. In vitro, EtOH treatment of bone marrow derived primary osteoblast (Ob) cultures from C57BL/6 mice which express Nox1, Nox2 and Nox4, resulted in induction of expression of receptor activator of NFκB ligand (RANKL) mRNA, an essential factor for osteoclast differentiation. However, no induction of RANKL was observed in cultures from p47phox -/- mice. Furthermore, in vitro studies with the pre-osteoblastic mouse ST-2 cell line demonstrated that EtOH-induced hydrogen peroxide production was inhibited by co-treatment with either 0.5 μM DPI or 5 μM of the Nox2 inhibitor gliotoxin. These data suggest that EtOH-induced bone loss is mediated at least in part by ROS generated via EtOH activation of Nox 1/2 enzymes in bone marrow Ob/pre-Ob and increased RANKL expression resulting in increased osteoclastogenesis and bone resorption. In addition, these data demonstrate that EtOHinhibition of bone formation occurs via a Nox1/2-independent mechanism. Supported in part by R01 AA018282 (M.J.R.) and Carl L. Nelson Chair in Orthopaedic Creativity (L.S.). 1303 INDUCTION OF OXIDATIVE DNA DAMAGE BY MESALAMINE IN THE PRESENCE OF COPPER: A POTENTIAL MECHANISM FOR MESALAMINE ANTICANCER ACTIVITY. Z. Jia 1, 2 , R. P. Zimmerman 1 , H. Zhu 1 , N. Vandjelovic 1 , H. P. Misra 1 , J. Wang 1 and Y. Li 1, 2 . 1 Edward via Virginia College of Osteopathic Medicine, Virginia Tech Corporate Research Center, Blacksburg, VA and 2 Department of Biomedical Sciences & Pathobiology, Virginia Polytechnic Institute and State University, Blacksburg, VA. Mesalamine is the first line pharmacologic intervention for patients with ulcerative colitis, and recent epidemiologic studies have demonstrated a protective association between therapeutic use of the drug and colorectal carcinoma. However, the mechanism by which this protection is afforded has yet to be elucidated. Because copper is found at higher than normal concentrations in neoplastic cell nuclei and is known to interact with phenolic compounds to generate reactive oxygen species, we investigated whether the reaction of mesalamine/copper was able to induce oxidative DNA strand breaks in φX-174 RF I plasmid DNA, and the various components of the mechanism by which the reaction occurred. Plasmid DNA strand breaks were induced by pharmacologically relevant concentrations of mesalamine in the presence of a micromolar concentration of Cu(II), and damage was inhibited by bathocuproinedisulfonic acid (BCS) and catalase. Further, we showed that the reaction of copper with mesalamine consumed molecular oxygen, which was inhibited by BCS. Electron paramagnetic resonance spectral analysis of the reaction of copper/mesalamine indicated the presence of the hydroxyl radical, which was inhibited by both BCS and catalase. This study demonstrates for the first time that through a copper-redox cycling mechanism, the copper-mediated oxidation of mesalamine is a pro-oxidant interaction that generates hydroxyl radicals which may participate in oxidative DNA damage. These results demonstrate a potential mechanism of the anticancer effects of mesalamine in patients with ulcerative colitis. 1304 EFFECT OF ZIDOVUDINE ON MITOCHONDRIAL OXIDATIVE PHOSPHORYLATION PROTEIN LEVELS AND ENZYME COMPLEX ACTIVITIES. J. Fang and F. A. Beland. Division of Biochemical Toxicology, National Center for Toxicological Research/U.S. FDA, Jefferson, AR. The nucleoside reverse transcriptase inhibitor zidovudine (3’-azido-3’-deoxythymidine; AZT) is used extensively for the treatment of AIDS and the prevention of the mother-to-child transmission of human immunodeficiency virus type I. In HIV-infected patients exposed to AZT, clinical evidence of mitochondrial dysfunction, such as morphologically-damaged mitochondria, an increase in lactic acid production and changes in mtDNA quantity, has been observed. The present study examines the effects of AZT on mitochondrial membrane potential (ΔΨm) and the levels of oxidative phosphorylation (OXPHOS) complex subunits and their activity. Mouse fibroblasts NIH3T3 cells and human hepatoma HepG2 cells were incubated with AZT in continuous culture for up to 4 weeks. Using the lipophilic cationic fluorescent dye JC-1 as a probe, the ΔΨm was determined by flow cytometry. In NIH3T3 cells, AZT (0 – 1000 μM) treatment led to a significant dose-dependent loss in ΔΨm. In contrast, HepG2 cells exposed to AZT (0 – 100 μM) had a significant dose-dependent increase in ΔΨm. Western-blot analysis indicated no significant differences in the levels of OXPHOS complex subunits (39 kDa subunit of complex I, 70 kDa subunit of complex II, core 1 subunit of complex III, cytochrome c oxidase subunit II of complex IV, and ATP synthase α of complex V) or porin in the mitochondria isolated from AZT-treated NIH3T3 cells or HepG2 cells, or from liver, heart, and skeletal muscle of B6C3F1/TK+/- and B6C3F1/TK+/+ mouse pups exposed to AZT transplacentally from gestation day 12. The activities of OXPHOS complexes II, III, IV, and V were also evaluated and, again, there were no significant differences. These data indicated that AZT treatments that cause changes in ΔΨm do not result in the alterations in mitochondria function. (Supported by Interagency Agreement 224-07-0007 between NCTR/FDA and NIEHS/NTP.) 1305 MECHANISMS BY WHICH GLYCERALDEHYDE-3- PHOSPHATE DEHYDROGENASE PROTECTS ITSELF AGAINST A CHEMICAL MODIFICATION. T. Miura 1 , Y. Egara 2 , R. Hirose 1 , N. Iwamoto 1 , Y. Shinkai 1 , A. K. Cho 3 and Y. Kumagai 1, 3 . 1 Doctoral Programs in Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan, 2 Master’s Program in Environmental Sciences, Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan and 3 Southern California Particle Center, University of California Los Angeles, Los Angeles, CA. Sponsor: A. Naganuma. Many cellular proteins with reactive thiols form covalent bonds with electrophiles that result in modification of structures and activities. Here we report that a glycolytic protein is able to recover from such covalent modification involving the electrophilic quinone, 1,2-naphthoquinone (1,2-NQ). We have found proteins that block the electrophilic attack by 1,2-NQ in the presence of NADH. Two dimensional SDS-PAGE and subsequent LC-MS/MS analysis revealed that a 37 kDa protein, identified as glyceraldehyde-3-phosphate dehydrogenase (GAPDH), was among them. This glycolytic enzyme readily underwent chemical modification by 1,2-NQ at a low concentration (0.2 μM) in a cell-free system, but exhibited minimal binding upon exposure to 1,2-NQ, even at 20 μM in human epithelial A549 cells while numerous other cellular proteins were extensively modified. In subsequent studies with purified human GAPDH, this enzyme was found to catalyze the reduction of 1,2-NQ to the non-electrophilic 1,2-dihydroxynaphthalene with NAD(P)H. Under these conditions, an NADH-dependent suppression of chemical modification of GAPDH by 1,2-NQ was observed. Although the adduct did form at high concentrations of 1,2-NQ, it underwent S-transalkylation with glutathione (GSH) to produce a GSH adduct of 1,2-NQ, which was associated with partial recovery of lost GAPDH activity. While GAPDH is well recognized to be a multifunctional protein, our results show that GAPDH also has a unique ability to repress its electrophilic modification by 1,2-NQ through 1) NAD(P)H-dependent two-electron reduction and 2) GSH-dependent S-transalkylation. 1306 METABOLISM DEPENDENT MODULATION OF 3, 4- (±)-METHYLENEDIOXYMETHAMPHETAMINE- INDUCED NEUROTOXICITY: POTENTIAL ROLE OF THIOETHER METABOLITES IN THE NEUROINFLAMMATORY RESPONSE. J. M. Herndon, A. B. Cholanians, G. V. Erives, X. Li, S. S. Lau and T. J. Monks. Pharmacology/Toxicology, University of Arizona - College of Pharmacy, Tucson, AZ. 3,4-(±)-Methylenedioxymethamphetamine (MDMA) abuse is a significant problem in the United States and around the world. Despite the widespread use of MDMA, relatively little is known about the underlying mechanisms of MDMA-induced neurotoxicity. We now describe studies on the role of metabolism in MDMA-induced neurotoxicity, as well as the potential role of thioether metabolites of MDMA in the neuroinflammatory response. Cytochrome P450 family member 2D6 (CYP2D6) and catechol-O-methyl transferase (COMT) participate in the metabolism of MDMA. These enzymes were inhibited in either pharmacological or genetic models to assess the effects of this inhibition on MDMA-induced neurotoxicity. Animals were administered a neurotoxic dose of MDMA (20 mg/kg sc - rats, 30 mg/kg sc x 3 at 3 hour intervals - mice) and neurotransmitter levels were determined by HPLC coupled to Electrochemical Detection, as a marker of neurotoxicity. For inflammatory studies, microglial activation was used as an indirect measure of inflammatory status in the CNS. Both IHC and a functional fluorescence assay were used to determine microglial activation. Inhibition of CYP 2D6 caused a marked attenuation of MDMA-induced neurotoxicity, whereas inhibition of COMT resulted in a potentiation of MDMA-induced neurotoxicity. Preliminary data indicates that peripheral administration of MDMA or direct intracranial injection of thioether metabolites of MDMA causes an increase in microglial activation 72 hours following administration. Perturbations in the enzymes that participate in the metabolism of MDMA result in a change in the neurotoxic profile presumably due to a change in the amount of thioether metabolites formed. When thioether metabolites are injected directly into the brain, an increase in microglial activation is observed, which could contribute to an inflammatory cascade in the CNS which exacerbates MDMA-induced neurotoxicity. SOT 2011 ANNUAL MEETING 279
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The Toxicologist Supplement to Toxi
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The Toxicologist Supplement to Toxi
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1 BIODEGRADABLE MATERIALS FOR TISSU
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that genetic toxicology data are ge
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well-orchestrated lung inflammation
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scribed in the literature. We have
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years ago). We will illustrate how
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involved in the biodegradation proc
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stem cells but rather a treatment i
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additional compound showed agreemen
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82 COMPARISON OF 3H-THYMIDINE INCOR
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irritants. While in practice these
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alleles are especially vulnerable t
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109 CD4+ T CELL INTRINSIC TNF RECEP
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118 TO STUDY THE SIGNAL TRANSDUCTIO
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PAHs, such as dioxins, are prevalen
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containing substituents and/or hydr
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146 COMPUTATIONAL MODELING FOR QT P
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suggest that the combination of too
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164 TRANSLOCATOR PROTEIN (18 KDA) (
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function as a metal binding protein
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laboratory has demonstrated that NR
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known. The aim of this study was to
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from 5 to 28 days in duration) in e
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positive cells, caspase-3 activatio
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creased level in the 46 kDa preproe
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invasiveness at concentrations repr
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thracene (DMBA,50 μg in acetone, a
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247 CO-CARCINOGENESIS OF N, N- DIET
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sponds to the endosomal dsRNA that
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ODD in both WT (maximum 177% of con
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Lastly, using p53siRNA cells, p53 w
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its receptor Mpl to exert its funct
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294 LOW LEVEL OF LEAD CAN INDUCE PH
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lunar surface presented potential h
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lar about cellular export mechanism
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DNA in the kidney medulla, grandula
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5.00 and 7.50 mg/kg/day by oral gav
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events and carcinogenesis. Here we
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tinization of cells of the hair fol
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358 CHARACTERIZATION OF GENOME-WIDE
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RNAi were also performed to identif
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376 A FUNCTIONAL CROSSTALK BETWEEN
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UGT1A gene induction, while this re
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tivity, specifically peroxisome pro
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and cytotoxic effects; however, its
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histone deacetylase that is necessa
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ment. Paradoxically, buthionine sul
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drug leflunomide and its major (A77
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442 GENE EXPRESSION AND MORPHOLOGIC
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451 INHIBITION OF THE MITOCHONDRIAL
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460 SULFORAPHANE PREVENTS ACETAMINO
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drophilic/lipophilic balance. Other
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pharmacokinetic and toxicological p
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489 USE OF ‘OMICS DATA TO IMPROVE
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498 APPLICATION OF AGE-SPECIFIC ADJ
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507 A DOSE VOLUME TOLERABILITY STUD
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involved the use of an acute inflam
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sorption in the gastrointestinal (G
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(ABC) transporters actively transpo
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545 BEHAVIORAL EFFECTS OF REPIN IN
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a blood pressure phenotype that res
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and inhalation exposure system that
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and lethality associated with these
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position, on vascular reactivity an
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therefore more accurate and reprodu
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commercial chrysotile product that
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elative to their controls. ST-depre
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ats. The majority of the studies fo
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in the China Jintan Child Cohort St
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corneum thickness, cellular epiderm
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645 EVALUATION OF THE IN VITRO EPIS
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654 TCDD ADSORBED ONTO NATURAL AND
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tion revealed no test article-relat
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671 INFLAMMATION AND TISSUE DAMAGE
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model, ethanol was found to inhibit
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689 ENHANCED SUPPRESSIVE FUNCTION O
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NAC + LPS yielded different levels
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707 LIFE-STAGE PBPK MODELS FOR MULT
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downstream of the apical endpoint o
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726 UPDATED ALUMINUM PHARMACOKINETI
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global parameter sensitivity analys
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and renal inflammation induced by 2
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754 PLASMA, URINE, AND TISSUE CONCE
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cently characterized transporter OA
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exposure system was developed from
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lood cell mass and decrease in urin
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practical alternatives to MC in non
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imals dosed with 167 mg/kg THU alon
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and organ weights, clinical signs a
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yet is induced in most bladder and
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830 RISK ASSESSMENT OF THE SPILL: C
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knowledgebase creation. Results are
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852 UNDERSTANDING STRUCTURAL AND PH
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for integrating epidemiology and an
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motor activity, including age of th
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y partial purification of urine (fr
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pacity for self-renewal and may dif
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sue. The depth of our analysis led
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910 IMPLEMENTING CALIFORNIA’S GRE
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concentrations in six tissues and b
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934 THE FDA’S LIVER TOXICITY KNOW
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943 GENOME-WIDE DNA METHYLATION DIF
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membrane localization and subsequen
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trols, respectively. Subtoxic and t
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survival using both smoking regimes
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as non-, weak, moderate, or strong
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988 NNK-INDUCED CYTOKINE ALTERATION
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group (one-way ANOVA, p90 % viabili
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ered as an organ involved in xenobi
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Transport of CPZ across the Caco-2
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estrous cycle and sexual behavior d
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mRNA expression levels. Collectivel
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1043 THE EFFECTS OF ENDOCRINE DISRU
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1052 MONO-2-ETHYLHEXYL PHTHALATE IN
Page 231 and 232: Results: MC was variable within and
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Page 239 and 240: events in the liver. AZD9056 was ev
Page 241 and 242: The peppermint oil caused a concent
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Page 245 and 246: 1126 PERSISTENT DEVELOPMENTAL ARYLH
Page 247 and 248: 1135 BACH2 BINDING TO Prdm1 AS A ME
Page 249 and 250: The purpose of this project was to
Page 251 and 252: one marrow. Since Chk1 is an attrac
Page 253 and 254: 1163 THE MRNA AND MIRNA PROFILE OF
Page 255 and 256: have now compared the IC50 values b
Page 257 and 258: 1181 ELUCIDATION OF FACTORS DETERMI
Page 259 and 260: enced by pre-exposure to cigarette
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Page 263 and 264: weight (P=0.016) and small for gest
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Page 267 and 268: posure groups. However, the differe
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Page 271 and 272: 1245 SEASONAL CHARACTERIZATION OF H
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Page 291 and 292: activity. The dose-response curves
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Page 299 and 300: 7d. 28d after TMT injury there was
Page 301 and 302: subunits. Each cell type was treate
Page 303 and 304: 1394 COMPARATIVE EFFECTS OF METHYLM
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Page 307 and 308: vated only in high-dose-treated ani
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Page 317 and 318: 1457 GLOBAL GENE PROFILING REVEALS
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1530 MINIMAL RISK LEVELS FOR STYREN
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ical groups in the field of regulat
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vitro with this potentially insect-
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their performance on toxicological
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need for a better understanding of
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1577 AN IN VITRO MODEL SYSTEM FOR A
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gene expression post-transcriptiona
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1595 GENE EXPRESSION PROFILE OF RAT
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to confirm a hepatotoxic property o
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1613 AN INVESTIGATION OF THE CLEARA
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its nuclear translocation was reduc
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were collected from TK animals at d
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egulated targets were selected for
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U/L after tetracycline. Minocycline
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peri-pubertal FasL-/- mice show a d
Page 363 and 364:
showed similar levels of apoptosis
Page 365 and 366:
1676 TWO BIOMARKERS FOR EVALUATION
Page 367 and 368:
motifs selected. This system was ap
Page 369 and 370:
1693 VOC SERUM LEVELS IN THE GENERA
Page 371 and 372:
1702 DOES THE CLOCK MAKE THE POISON
Page 373 and 374:
those with high nickel content are
Page 375 and 376:
isk assessment. However, unique cha
Page 377 and 378:
model of APAP metabolism and glutat
Page 379 and 380:
logically & morphologically similar
Page 381 and 382:
posure, blood chemistry was analyze
Page 383 and 384:
elated to oxidative stress by measu
Page 385 and 386:
ostasis), but work is needed to tra
Page 387 and 388:
tokine products during carcinogenes
Page 389 and 390:
ways as chemical stressors and, the
Page 391 and 392:
toxicity of nanomaterials relates s
Page 393 and 394:
1815 MEASURING COMPOUND SELECTIVITY
Page 395 and 396:
1825 EFFECTS OF METABOLISM BY INTES
Page 397 and 398:
cyanoacetic acid increased 2-3 fold
Page 399 and 400:
1845 IS THE PROMISCUITY OF THE ARYL
Page 401 and 402:
crorarray analysis. RT-PCR results
Page 403 and 404:
are a family of phase-II biotransfo
Page 405 and 406:
ous labs. As a result of positive s
Page 407 and 408:
down the doses may produce more tox
Page 409 and 410:
spectively. Below 100 mg/l of gemfi
Page 411 and 412:
1900 GENERATION OF PRECISION CUT LI
Page 413 and 414:
iomarkers or observation of lesions
Page 415 and 416:
creased reticulocytes and lymphocyt
Page 417 and 418:
statistically significant interacti
Page 419 and 420:
monize sample preparation and analy
Page 421 and 422:
NPC and sinonasal cancer in neighbo
Page 423 and 424:
showed incidences of lung and nasal
Page 425 and 426:
utylbenzenes, exhibited most simila
Page 427 and 428:
1975 DIFFERENTIAL MODULATION OF CYP
Page 429 and 430:
organic As to MMA(V) and a lower ca
Page 431 and 432:
ole in invasion and metastasis of c
Page 433 and 434:
3T3-L1 cells to low-levels of arsen
Page 435 and 436:
2011 IDENTIFICATION OF A NOVEL VX M
Page 437 and 438:
This work was supported by Cooperat
Page 439 and 440:
2029 EFFICACY OF ENDOTRACHEAL ADMIN
Page 441 and 442:
Diazepam injections and its combina
Page 443 and 444:
2047 ESTERASE ACTIVITIES AND HEMOST
Page 445 and 446:
nanoparticle-induced toxicity progr
Page 447 and 448:
house, were iv infused into rats ov
Page 449 and 450:
een explored. This study investigat
Page 451 and 452:
croscopic analysis revealed that on
Page 453 and 454:
egg yolk collected from turtles inh
Page 455 and 456:
consistency of results in both expe
Page 457 and 458:
2111 CYTOCHROME P450 3A5 GENOTYPE I
Page 459 and 460:
esidues of organophosphates or thei
Page 461 and 462:
manganism. Recent work from our lab
Page 463 and 464:
Aβ1-40 in CSF and hippocampus in P
Page 465 and 466:
2147 CATALASE MANIPULATIONS MODIFY
Page 467 and 468:
ation based on real-world exposure
Page 469 and 470:
NPs. Aggregation of citrate-stabili
Page 471 and 472:
2175 THE ROLE OF SURFACE CHEMISTRY
Page 473 and 474:
seen rapid uptake in biological ima
Page 475 and 476:
effect on uterine weight or vaginal
Page 477 and 478:
dicating widespread exposure. While
Page 479 and 480:
components into the liver parenchym
Page 481 and 482:
2223 ISOLATION AND DETECTION OF RIC
Page 483 and 484:
stored (-20 celsius degree). The co
Page 485 and 486:
2241 DDA, A BIOMARKER FOR ENVIRONME
Page 487 and 488:
2249 INTERACTION BETWEEN DIETARY SE
Page 489 and 490:
2258 PHARMACOKINETICS, EXCRETION BA
Page 491 and 492:
2267 SENSITIVE AND SPECIFIC FLUORES
Page 493 and 494:
2276 METABOLISM AND DISPOSITION OF
Page 495 and 496:
ment of hypertension in companion a
Page 497 and 498:
for the propyl series can be used f
Page 499 and 500:
2304 IN VITRO EXPOSURE AND EVALUATI
Page 501 and 502:
2313 THE SYNERGISTIC EFFECT OF SODI
Page 503 and 504:
genes that play a crucial role in M
Page 505 and 506:
2330 THE ROLE OF TRANSFORMING GROWT
Page 507 and 508:
ined following up to 96 h continuou
Page 509 and 510:
effect doses obtained with the rat
Page 511 and 512:
diated transcriptional response of
Page 513 and 514:
docrine disruptor activities of EDC
Page 515 and 516:
individuals. Week 6 results were qu
Page 517 and 518:
functionality of photosystem II and
Page 519 and 520:
wild mice (Mus musculus) from areas
Page 521 and 522:
2406 TOXICITY AND BIOACCUMULATION O
Page 523 and 524:
Isocitric acid is the acid in the h
Page 525 and 526:
2425 EFFECTS OF FUMONISINS IN ETHAN
Page 527 and 528:
centration(μg/g) were: 5.1-95.3; 2
Page 529 and 530:
2445 AUTOPHAGY IN DEVELOPMENT: A LI
Page 531 and 532:
sures to inhaled Mn in dust. Nevert
Page 533 and 534:
2466 CRITICAL EVALUATION OF ANIMAL
Page 535 and 536:
elationships predict that resting r
Page 537 and 538:
2489 COMPARATIVE TOXICITY OF BIODIE
Page 539 and 540:
2497 TRANSCRIPTIONAL REGULATION OF
Page 541 and 542:
2506 TOXICOLOGICAL CONSIDERATIONS O
Page 543 and 544:
launched with the aim of developing
Page 545 and 546:
forms mRNA expression levels were a
Page 547 and 548:
2534 CUTANEOUS WOUND HEALING IN THE
Page 549 and 550:
wells (0, 1, 5, 10, 25, 50, 100, an
Page 551 and 552:
2553 AN ORGANOTYPIC MICROLIVER PLAT
Page 553 and 554:
serum-free media. At 24 hrs, the gr
Page 555 and 556:
2572 INCREASED ARSENIC BIOACCESSIBI
Page 557 and 558:
nology to develop improved methods.
Page 559 and 560:
tuna, swordfish, or mako shark (3.5
Page 561 and 562:
nificantly reduce circulating thyro
Page 563 and 564:
grouped into 9 observation periods
Page 565 and 566:
histopathological or biochemical ev
Page 567 and 568:
exhibited a hyperactive phenotype,
Page 569 and 570:
the search of effective drugs for e
Page 571 and 572:
2644 COVALENT BINDING OF 14 C 2-MET
Page 573 and 574:
aries targeting all transcription f
Page 575 and 576:
(p 9 weeks) and CSC phenotype acqui
Page 577 and 578:
2673 IMMUNE-MEDIATED VASCULAR INJUR
Page 579 and 580:
for risk identification and charact
Page 581 and 582:
to control toxicant delivery in tob
Page 583 and 584:
Author Index (Continued) The numera
Page 585 and 586:
Page 587 and 588:
Page 589 and 590:
Page 591 and 592:
Page 593 and 594:
Page 595 and 596:
Page 597 and 598:
Page 599 and 600:
Page 601 and 602:
Page 603 and 604:
Page 605 and 606:
Page 607 and 608:
Page 609 and 610:
Page 611 and 612:
Keyword Index (Continued) Arsenite
Page 613 and 614:
Keyword Index (Continued) Covalent
Page 615 and 616:
Keyword Index (Continued) flow cyto
Page 617 and 618:
Keyword Index (Continued) innate im
Page 619 and 620:
Keyword Index (Continued) nanoparti
Page 621 and 622:
Keyword Index (Continued) preservat
Page 623 and 624:
Keyword Index (Continued) Thrombocy
Page 625 and 626:
Toxicological Sciences The Official
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