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cortactin and Hsp90. HDAC6 interacts with Ras-GTPase-activating protein SH3 domain-binding protein 1 (G3BP) under stress conditions, facilitating protein locomotion and stress granule formation. To address whether HDAC6 mediates cellular response to Arsenite stress, we used HaCat keratinocytes for treatment with Sodium Arsenite. Sodium Arsenite induced a morphological change characteristic of cellular condensing. Immunocytochemistry experiments revealed HDAC6 relocalized to the perinuclear space during Sodium Arsenite-induced stress within 30 minutes. There was no difference in the overall level of HDAC6 protein with various doses of Sodium Arsenite by Western blot analyses. Perinuclear localization of HDAC6 correlates with a dose dependent increase of association with polysomes. These results suggest HDAC6 interacts with ribosomal proteins. Several ribosomal proteins were examined by immunocytochemistry to determine co-localization with HDAC6. We found that Sodium Arsenite caused HDAC6 to co-localize with L36a ribosomal proteins. Immunoprecipitation experiments indicate physical interaction of HDAC6 with ribosomal protein L36a. This study demonstrated that HDAC6 is recruited to the polysomes during stress and interacts specifically with ribosomal protein L36a. This finding may provide a better understanding of ribosomal regulation during stress through post-translation modifications of specific ribosomal subunits. 1280 POST-TRANSLATIONAL MODIFICATION AND REGULATION OF GLUTAMATE CYSTEINE LIGASE BY THE α, β-UNSATURATED ALDEHYDES ACROLEIN AND 4-HYDROXYNONENAL. D. S. Backos 1 , K. S. Fritz 1 , J. R. Roede 2 , D. R. Petersen 1 and C. C. Franklin 1 . 1 Department of Pharmaceutical Sciences, University of Colorado Denver, Denver, CO and 2 Department of Medicine, Pulmonary Division, Emory University, Atlanta, GA. Acrolein and 4-hydroxynonenal (4-HNE) are cytotoxic α,β-unsaturated aldehydes produced via lipid peroxidation. These reactive aldehydes can alter protein function by direct covalent modification of nucleophilic amino acid residues (Cys, His, Lys, (Arg)). Mammalian cells possess a number of antioxidant defense mechanisms to counteract the deleterious effects of oxidative stress and reactive aldehydes. The glutathione (GSH) antioxidant defense system plays a critical role in maintaining cellular redox homeostasis and detoxification of reactive aldehydes via GSH conjugation. The first and rate-limiting step in GSH biosynthesis is catalyzed by glutamate cysteine ligase (GCL), a heterodimeric holoenzyme composed of a catalytic (GCLC) and modulatory (GCLM) subunit. In this study, purified recombinant proteins were utilized to demonstrate that GCLC and GCLM are targets for posttranslational modification by acrolein and 4-HNE. While both aldehydes inhibited GCL holoenzyme formation and activity, they differentially affected monomeric GCLC activity. 4-HNE activated GCLC, while acrolein had a biphasic effect on GCLC enzymatic activity. Residue masking studies indicated that Cys and Lys residues were the primary targets of adduction on both GCL subunits. Furthermore, mass spectrometry analysis identified several residues that were differentially modified by acrolein and 4-HNE, and may be functionally relevant based on in silico molecular modeling. In aggregate, these findings demonstrate that acrolein and 4-HNE can alter GCLC activity and GCL holoenzyme formation and activity via direct post-translational modification of the GCL subunits in vitro. Within a cellular context, this novel post-translational regulation of GCL activity could significantly affect cellular redox homeostasis and GSH-dependent detoxification during periods of oxidative stress. 1281 IDENTIFICATION OF HYDROIMIDAZOLONE AND ARGPYRIMIDINE ADDUCTS AS GLYCOOXIDATIVE BIOMARKERS IN TYPE 2 DIABETIC SUBJECTS. O. Kinsky 1 , M. J. Kimzey 1 , H. N. Yassine 2 , C. S. Stump 2 , G. Tsaiprailis 1 , T. J. Monks 1 and S. S. Lau 1 . 1 Southwest Environmental Health Sciences Center, Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson, AZ and 2 College of Medicine, University of Arizona, Tucson, AZ. Oxidative stress and advanced glycation (glyco-oxidation) produce reactive dicarbonyls such as methylglyoxal (MG), 3-deoxyglucosone and glucosone. Dicarbonyls primarily react with arginine residues, resulting in irreversibly modified proteins as a consequence of the net loss of positive charge via hydroimidazolone and, to a lesser extent, argpyrimidine ring formation. These dicarbonyl adducts on human serum albumin (HSA) may be useful as candidate biomarkers for oxidative stressrelated diseases. We employed multiple-reaction monitoring (MRM) on 12 synthetic HSA peptides, with three dicarbonyl modifications each, to generate a transition list to quantitate relative modification at each site. In addition to MRM, we determined whether MG-modified HSA was detectable in the urine of type II diabetes patients (T2D) with macroalbuminuria. Digests of the dicarbonyl modified HSA revealed R410 as the dominant hotspot in vitro for MG, 3-deoxyglucosone, and glucosone. In addition to R410, both R257 and R186 were found to be 274 SOT 2011 ANNUAL MEETING hotspots as well, with R186 being the least reactive of the three sites. Western blot analyses using anti-MG antibody on urine from T2D patients with macroalbuminuria indicated detectable levels of MG-related modifications on several proteins, primarily albumin. From the MRM data, we have determined that quantitation of glyco-oxidation from reactive dicarbonyls is suitable using tandem LC-MS/MS analysis. In summary, using two complementary approaches we have identified MG-modified HSA by MRM in plasma and western blot analysis in urine from T2D patients with macroalbuminuria. MG-protein modifications of plasma and/or urinary proteins may serve as markers of diabetic complications. (P30ES006694, R24DK083948, T32 ES016652, ABRC 10-100). 1282 IDENTIFICATION AND CHARACTERIZATION OF 4- HNE MODIFIED LIVER FATTY ACID BINDING PROTEIN IN A RODENT MODEL OF EARLY ALCOHOLIC LIVER DISEASE. R. L. Smathers, K. S. Fritz, J. J. Galligan, C. T. Shearn and D. R. Petersen. Pharmaceutical Sciences, University of Colorado Denver, Aurora, CO. Chronic ethanol consumption is a prominent cause of liver disease and is responsible for significant morbidity and mortality throughout the Western world. Among the predictable and prominent histologic abnormalities resulting from ethanol ingestion is hepatosteatosis (fatty liver). The mechanisms behind the observed fluctuations in lipid homeostasis include, but are not limited to, increased hepatocellular synthesis and decreased β-oxidation of fatty acids, as well as impairment of cellular trafficking and secretion of hepatic lipids. Using a proteome-wide scan of cellular extracts prepared from livers of mice ingesting alcohol for 6 weeks, we identified liver fatty acid binding protein (L-FABP) as a target for modification by the aldehydic product of lipid peroxidation, 4-hydroxynonenal (4-HNE). Utilizing LC- MS/MS and MALDI-TOF/TOF mass spectrometry, residues susceptible to modification by 4-HNE were identified at H43, C69, K31 and K57 from purified recombinant mouse L-FABP (rL-FABP). Saturation isothermic analysis of 4-HNEtreated rL-FABP revealed significant reductions in maximal binding and markedly altered high- and low-affinity dissociation constants for the fluorescent probe, 1anilinonaphthalene-8-sulfonic acid (ANS). Stability of adducted protein was also analyzed via thermal denaturation, demonstrating the detrimental effects of 4- HNE modification to L-FABP. Significant changes in the compartmental expression of L-FABP, expression and activity of peroxisome proliferator activated receptor-alpha (PPAR-α), and ubiquitinated proteins were observed in ethanol-treated mice. Immunohistochemical evaluation of liver sections also revealed considerable changes in lobular expression and localization of L-FABP. Collectively, these data demonstrate in vivo and in vitro modification of L-FABP by 4-HNE; suggesting L- FABP as a potential target for study of the initiation and progression of alcoholic liver disease. (R37 NIH/AA009300; NIH/NIAAA 5F31 AA18898-02) 1283 EXTENSIVE OXIDATIVE PROTEIN MODIFICATIONS OBSERVED IN HUMAN PLASMA AND CANDIDATE BIOMARKERS OF SYSTEMIC CHRONIC INFLAMMATORY AND OXIDATIVE STRESS. X. Zhang, M. A. Gritsenko, B. Webb-Robertson, K. M. Waters, D. J. Bigelow, W. Qian, J. G. Pounds and J. M. Jacobs. Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA. Smoking and obesity are two of the most important, yet preventable risk factors for human morbidity and mortality. Chronic inflammation and oxidative stress appears to be the unifying mechanism underlying the interaction of these risk factors with the genome, resulting in a variety of chronic human diseases. We are identifying potential protein biomarkers of oxidative stress in human populations that accurately and quantitatively reflect an individual’s exposure/response to environmental stressors. A subset of plasma samples were analyzed from a cohort of 500 exposed to main-stream tobacco smoke or never-smoked with BMI above 35 or below 25. The four representative pooled groups included high BMI smoker and non-smokers, and low BMI smoker and non-smokers. Individual human plasma in each group was pooled, depleted, digested with trypsin, with the resulting peptides fractionated using SCX chromatography and subsequently analyzed via an LTQ- Orbitrap mass spectrometer for a total of 100 LC-MS/MS analyses. Data were searched using X!Tandem against the human International Protein Index database resulting in 9908 confident peptide identifications corresponding to 1306 proteins. Searches for 5 different oxidative modifications on tyrosine residues and 2 on cysteine residues resulted in >1500 unique modified peptides. Extensive oxidation of plasma proteins was observed, some with multiple modifications. Dopa-quinone and cysteine sulfonic modifications of AT and alpha-2M were of interest because oxidative modification of these proteins is known to contribute to disease risk and development. The differential abundance of modified peptides from several pro-
teins (e.g. C3, 4, and 5, APOB, VDBP, alpha-1 ACT, and ITIH1) were highly effective in classifying plasma samples to phenotype. These proteins should provide insights into systemic chronic inflammation, serve as biomarkers, or new drug targets for intervention. Supported by NIEHS U54016105 1284 EXTENSIVE OXIDATIVE PROTEIN MODIFICATIONS OBSERVED IN HUMAN PLASMA AND CANDIDATE BIOMARKERS OF SYSTEMIC CHRONIC INFLAMMATORY AND OXIDATIVE STRESS. B. Webb-Robertson, X. Zhang, K. M. Waters, W. Qian, J. M. Jacobs, D. J. Bigelow, R. Corley and J. G. Pounds. Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA. Smoking and obesity are two of the most important, yet preventable risk factors for human morbidity and mortality. Chronic inflammation and oxidative stress appears to be the unifying mechanism underlying the interaction of these risk factors with the genome, resulting in a variety of chronic human diseases. We are identifying potential protein biomarkers of oxidative stress in human populations that accurately and quantitatively reflect an individual’s exposure/response to environmental stressors. A subset of plasma samples were analyzed from a cohort of 500 exposed to main-stream tobacco smoke or never-smoked with BMI above 35 or below 25. Eight plasma samples per group representing high BMI smoker and nonsmokers, and low BMI smoker and non-smokers were Individual human plasma were depleted, digested with trypsin and analyzed via an LTQ-Orbitrap mass spectrometer in triplicate. Peptides were identified by accurate mass and time (AMT) tags. 4616 peptides passed quality control and were analyzied by ANOVA and Gtest for statistical significance to experimental groups. 133 proteins are significant for either smoking status or BMI. 94 of these proteins had at least one oxidatively modified proteins. Statistical and graphical analysis revealed that the abundance of unmodified peptides are typically similar across the four groups while the abundance of modified peptides is group specific. This trend is particularly noted for the proteins Complement factor D, Plasminogen-like B2, and Fibrinogen. The differential abundance of modified 0and unmodified peptides/proteins were highly effective in classifying plasma samples to phenotype. These proteins should provide insights into systemic chronic inflammation, serve as biomarkers, or new drug targets for intervention. Supported by NIEHS U54016105 1285 DEVELOPMENT OF MALDI-TOF METHODOLOGY FOR SELECTIVE MS-ANALYSIS AND IMAGING OF CARDIOLIPINS IN LIPID EXTRACTS AND TISSUES. L. J. Sparvero 1, 3 , A. Amoscato 1, 3 , B. R. Pitt 1, 3 , H. Bayir 2, 3 and V. E. Kagan 1, 3 . 1 Center for Free Radical and Antioxidant Health, Environmental and Occupational Health, Pittsburgh, PA, 2 Critical Care Medicine, Safar Center for Resuscitation Research, Pittsburgh, PA and 3 University of Pittsburgh, Pittsburgh, PA. Cardiolipin (CL) is an anionic phospholipid that plays a key role in mitochondrial electron transport but is also highly susceptible to oxidative stress. The molecular diversity of endogenous cardiolipins in some tissues and the low abundance of its individual species, particularly oxidized derivatives, makes in situ analysis and imaging by MALDI-Mass Spectrometry (MALDI-MS) challenging. The goal of this study was to develop a method to selectively analyze CL using existing CL probes in a novel way, to decrease CL mass spectral complexity. Nonyl Acridine Orange (NAO) is a commonly used fluorescent stain for cardiolipin. We have used NAO as a novel MALDI matrix, and have found that it allowed detection of anionic phospholipids, including cardiolipin in the negative ion mode. With careful laser tuning, NAO induced prompt decay of cardiolipin selectively - but not other phospholipids - at very high efficiencies. From these selective prompt decay products, much information about the structure of cardiolipin can be determined. Pseudo- MS 3 is possible on a MALDI-TOF instrument by doing MS/MS on these products of cardiolipin. We have also extended these findings to include oxidized species of CL’s and have determined that NAO also induced prompt decay of oxidized CL. Prompt fragments are seldom seen with dihydroxy-benzoic acid (DHB) which has been employed as a standard matrix for lipid analysis in the negative ion mode. Our results indicate that NAO can be utilized as a discerning matrix for the assessment of CL in lipid extracts from cells and the distribution of CL - particularly in tissues with a high diversity of CL molecular species and their oxidation products - by taking full advantage of the unique ability to induce prompt decay of this phospholipid with NAO. Supported by grants from NIH (NS061817, HL70755, U19 AIO68021, HD05758, HL094488); NIOSH (OH008282). 1286 PROTEOMIC IDENTIFICATION OF NITRATED PROTEINS IN THE SPLEEN OF ANILINE EXPOSED RATS. X. Fan 1 , J. Wang 1 , K. Soman 2 , G. Ansari 1, 2 and M. Khan 1 . 1 Pathology, University of Texas Medical Branch, Galveston, TX and 2 BMB, University of Texas Medical Branch, Galveston, TX. Aniline exposure is associated with toxicity to the spleen. However, mechanisms by which aniline elicits splenotoxic response are not well understood. Earlier we have shown that aniline exposure leads to increased nitration of proteins in the spleen. However, nitrated proteins remain to be identified and characterized. Identification of nitrated proteins is important because nitration of proteins could result in their inactivation, increased degradation and altered tyrosine phosphorylation, and thus, could contribute to splenic toxicity. Therefore, the current study, using proteomic approaches (2D Western blot, MALDI TOF/TOF MS/MS and Progenesis SameSpots, etc.), was focused on identifying and characterizing nitrated proteins in the spleen of aniline exposed rats (0.5 mmol/kg/day for 30 days via drinking water). Aniline exposure led to increased tyrosine nitration of proteins, as determined by 2D Western blotting with specific anti-3-nitrotyrosine antibody, compared to the controls. The nitrated proteins were found in the molecular weight range from 27.7 to 123.6 kDa. A total of 37 nitrated proteins were identified in the protein extracts of aniline-treated and control spleens. Among them, 25 were found only in anilinetreated rats, 11 were present in both aniline-treated and control rats, while one nitrated protein was found in controls only. The nitrated proteins identified mainly represent skeleton proteins, chaperones, ferric iron transporter, enzymes, nucleic acids binding protein, and signaling and protein synthesis pathways. The increased nitration of proteins not only supports our previous findings, but more importantly, provides a global map to further investigate alterations in their structural and functional properties, and thus, a better understanding of the role of the protein nitration in splenic toxicity. Supported by NIH ES006476. 1287 CIRCULATING LEVELS OF NITRATED PROTEINS ARE SUPPRESSED BY CIGARETTE SMOKING. R. Zangar 1 , H. Jin 1 , B. Webb-Robertson 1 , D. Bigelow 1 , M. Scholand 2 , J. Hoidal 2 and J. Pounds 1 . 1 Pacific Northwest National Laboratory, Richland, WA and 2 Health Sciences Center, University of Utah, Salt Lake City, UT. Nitric oxide (NO) is a physiological regulator of endothelial function and hemodynamics. Oxidized products of NO can form nitrotyrosine in proteins, a general marker of nitrative stress. Cigarette smoking decreases exhaled NO, and the underlying mechanism may be important in cardiovascular toxicity. Even so, it is unclear if this decrease in exhaled NO is due to lower NO production or increased NO degradation to nitrating species. Since these two processes should have opposing effects on nitrotyrosine levels, our goal was to examine nitration levels in circulating proteins in order to gain insight into which of these processes predominates in smokers. A custom antibody microarray platform was developed to analyze the levels of 3-nitrotyrosine modifications on 24 proteins in plasma. Plasma samples from 458 individuals including non-smokers, former smokers, and active smokers with or without chronic obstructive pulmonary disease (COPD) were analyzed. Levels of nitrated plasma proteins were consistently lower in current and former smokers than in plasma from non-smokers; protein nitrotyrosine levels in individuals at risk for environmental cigarette smoke exposure was intermediate between smokers and non-smokers. These results are consistent with evidence that soluble cigarettesmoke components suppress endothelial NO synthase activity, leading to endothelial dysfunction and cardiovascular disease. In contrast, we observe an increase in nitrotyrosine levels in individuals with COPD that likely reflects an increase in inflammation. This study provides the first evidence that smoking has irreversible effects on endothelial production of nitric oxide in humans, and provides insight into how smoking could induce endothelial dysfunction and a long-term increase in the risk of cardiovascular disease. Supported by NIEHS Exposure Biology Program, U54 ES106015. 1288 URINARY 8-OXO-DEOXYGUANOSINE IN SMOKERS: ASSOCIATIONS WITH RACE, SEX, AND MENTHOL SMOKING. M. Misra and D. Ergle. Lorillard Tobacco Company, Greensboro, NC. Several recent studies have found no significant differences in either biomarkers of exposure or biomarkers of potential harm in the blood and urine of menthol smokers compared to non-menthol smokers. Differential uptake or metabolism of cigarette smoke constituents can induce oxidative stress and lead to the oxidative modification of the guanine base of DNA. This modification results in the formation of SOT 2011 ANNUAL MEETING 275
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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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Page 229 and 230: 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
Page 261 and 262: if abnormal PF was associated with
Page 263 and 264: weight (P=0.016) and small for gest
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Page 287 and 288: luted OFR and CRL. Culture media ex
Page 289 and 290: urinary TCPy levels, blood and brai
Page 291 and 292: activity. The dose-response curves
Page 293 and 294: mice, each with 4 dose groups. One
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Page 297 and 298: third tetratricopeptide repeats (TP
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
Page 309 and 310: 1421 DOSE-RESPONSE OF NAPHTHALENE-I
Page 311 and 312: cisplatin; 1.2-, 1.9- and 2.9-fold
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Page 315 and 316: 1448 DEVELOPMENT OF A METHOD FOR QU
Page 317 and 318: 1457 GLOBAL GENE PROFILING REVEALS
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(CIA) and the Streptococcal cell wa
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sitizers were 100% concordant among
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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
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showed similar levels of apoptosis
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1676 TWO BIOMARKERS FOR EVALUATION
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motifs selected. This system was ap
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1693 VOC SERUM LEVELS IN THE GENERA
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1702 DOES THE CLOCK MAKE THE POISON
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those with high nickel content are
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isk assessment. However, unique cha
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model of APAP metabolism and glutat
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logically & morphologically similar
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posure, blood chemistry was analyze
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elated to oxidative stress by measu
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ostasis), but work is needed to tra
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tokine products during carcinogenes
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ways as chemical stressors and, the
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toxicity of nanomaterials relates s
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1815 MEASURING COMPOUND SELECTIVITY
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1825 EFFECTS OF METABOLISM BY INTES
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cyanoacetic acid increased 2-3 fold
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1845 IS THE PROMISCUITY OF THE ARYL
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crorarray analysis. RT-PCR results
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are a family of phase-II biotransfo
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ous labs. As a result of positive s
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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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