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cells with MeHg. N-acetylcysteine effectively reversed the MeHg-induced cell apoptosis-related signals. Taken together, our data suggest that MeHg-induced oxidative stress causes pancreatic β-cells apoptosis, and both mitochondrial-dependent and ER stress- mediated apoptotic signals involve in the MeHg-induced pancreatic β-cells death. 308 ROLES OF RIP1 AND YIL006W, MITOCHONDRIAL PROTEINS, IN METHYLMERCURY TOXICITY IN BUDDING YEAST. J. Lee, G. Hwang and A. Naganuma. Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan. Methylmercury (MeHg) is an environmental pollutant that causes severe damage in central nervous system. However, the molecular mechanism of MeHg toxicity is not fully understood. Several investigators have demonstrated that mitochondria are potentially involved in MeHg toxicity. In order to characterize functional relationship between MeHg toxicity and mitochondria, we searched for mitochondrial proteins involved in MeHg toxicity in budding yeast. Yeast is a genetically wellcharacterized eukaryotic organism that shares many genes common with mammals, including humans. We recently found that yeast cells deficient in Yil006w exhibited resistance to MeHg as compared to wild-type yeast. Yil006w is one of the transporter families existing in inner-membrane of mitochondria. Overexperssion of Yil006w conferred hypersensitivity to MeHg. Moreover, not only cellular protein level, but also mRNA level of Yil006w was increased by MeHg treatment. Mitochondrial level of Yil006w was also increased by treatment of MeHg. These results suggested that MeHg might increase the mitochondrial Yil006w level and strengthen its toxicity. We previously demonstrated that Rip1, a component of mitochondrial electron transfer chain complex III, was potentially involved in the production of reactive oxygen species (ROS) in response to MeHg. Therefore, we examined relationship between Rip1 and Yil006w in MeHg toxicity. We treated yeast cells, which lacked both Rip1 and Yil006w, with MeHg. The degree of resistance to MeHg was not increased by the deletion of both Rip1 and Yil006w as compared to each single-deletion mutants, suggesting that Rip1 and Yil006w strengthen MeHg toxicity through a mechanism involved in a common pathway. We also found that the increase of ROS level induced by MeHg was significantly attenuated in Yil006w-deficient yeast. Thus, Yil006w might have a major role in the mechanism of Rip1-enhanced ROS generation in response to MeHg. 309 MERCURY MODULATE THE CYTOCHROME P450 1A1 IN C57BL/6 MICE: IN VIVO AND IN VITRO STUDIES. I. Amara and A. El-kadi. Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB, Canada. Heavy metals, such as mercury (Hg2+), and aryl hydrocarbon receptor (AhR) ligands such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) are environmental cocontaminants and their molecular interaction may disrupt the coordinated regulation of the carcinogen-activating enzyme cytochrome P4501a1 (Cyp1a1). Therefore, in the current study we examined the effect of Hg2+ on the expression of Cyp1a1 in C57BL/6 mice livers and isolated mouse hepatocytes. For this purpose, C57BL/6 mice were injected intraperitoneally with Hg2+ (2.5 mg/kg) in the absence and presence of TCDD (15 μM/kg). After 6 and 24 h the tissue was harvested and the expression of Cyp1a1 mRNA, protein and catalytic activity levels were determined using real time-PCR, Western blot and 7-ethoxyresorufin Odeethylase (EROD) analyses, respectively. In vitro, isolated mouse hepatocytes were incubated with TCDD (1 nM) in the presence and absence of various concentrations of Hg2+ (2.5, 5 and 10 μM). Our results demonstrate that at in vivo level, Hg2+ significantly decreased the TCDD-mediated induction of Cyp1a1 mRNA at 6 h while potentiating its mRNA, protein, and catalytic activity levels at 24 h. At in vitro level, Hg2+ significantly inhibited the TCDD-mediated induction of Cyp1a1 at mRNA, protein and activity levels in a concentration-dependent manner. Investigating the effect of Hg2+ at transcriptional levels revealed that Hg2+ significantly inhibited the TCDD-mediated induction of AhR-dependent luciferase reporter gene expression. In conclusion, caution should be taken when extrapolating in vitro data to in vivo situation. Furthermore, our results indicate more complex regulation of Cyp1a1 at the in vivo level that warrants further investigation. Funded by NSERC Discovery Grant RGPIN 250139-07. 66 SOT 2011 ANNUAL MEETING 310 ASSESSING METAL LEVELS IN CHILDREN FROM THE MECHANISTIC INDICATORS OF CHILDHOOD ASTHMA (MICA) STUDY. A. Sanders 1 , J. Gallagher 2 , J. McGee 2 , S. Rhoney 2 , E. Hugens 2 , H. Özkaynak 3 and R. Fry 1 . 1 Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, 2 National Health Environmental Effects Research Laboratory, U.S. EPA, Research Triangle Park, NC and 3 National Exposure Research Laboratory, U.S. EPA, Research Triangle Park, NC. Toxic and essential metals levels can be used as health indicators. Here we quantitatively compare and contrast toxic and essential metals levels in vacuum dust, urine, and fingernail samples of 109 children in Detroit, Michigan as part of The Mechanistic Indicators of Childhood Asthma (MICA) study – a study aimed at examining relationships between exposure and biomarkers of exposure effects and susceptibility in children ages 9-13. Comparison of the Detroit children’s urinary levels with the CDC’s Fourth National Report on Human Exposure to Environmental Chemicals showed that urinary metal levels for As, Cd and Pb, were similar to nationally reported levels. Creatinine-adjusted urinary metal concentrations were in the order: Zn >> Se > Cu > As > Ni > Pb > Cd > Cr > V > Mn. We find no statistical differences in essential metals levels between children with varied vitamin use status. Our results indicate that levels of toxic metals indeed covary with each other as well as with essential metals (e.g. arsenic and selenium) in the biological matrices. Furthermore, among all possible pairwise comparisons of metals and media types, metals levels in the matrices representing chronic exposure (nails and dust) were more closely associated relative to the short term exposure indicator (urine). This study underscores the importance for the consideration of both individual and multiple metals in health effect studies. This abstract is the text of a proposed presentation and does not represent EPA policy. 311 BRIDGING THE MISSING LINK IN PRINCIPLE THEORY – SELENIUM TRANSPORT IN ENTEROCYTES AND HEPATOCYTES. S. Misra 1 , R. W.M. Kwong 2 and S. Niyogi 1 . 1 Biology, University of Saskatchewan, Saskatoon, Saskatchwean, Canada and 2 Toxicology Centre, University of Saskatchewan, Saskatoon, Saskatchwean, Canada. Selenium (Se) is a unique trace element with diverse physiological functionality. In contrast, it exhibits very low margin between essentiality and toxicity. Recent research reveals potential applications of Se in cancer prevention and treatment. Nevertheless, a simple, yet basic research question remains to be understood in depth – how Se is transported in higher eukaryotic cells? To address this, the present study was designed to evaluate Se transport kinetics at physiological concentrations using isolated rainbow trout hepatocytes and enterocytes as model systems. Selenite transport was linear in both cell types at the concentration range tested. However, pre-incubation of selenite with glutathione (GSH) resulted in increased Se uptake with saturable uptake kinetics in enterocytes but not in hepatocytes during early uptake phase. L-cysteine, another thiol-group containing agent, increased Se uptake in both cell types by ∼10-folds when pre-incubated with selenite. Inhibitory effects of anionic transporter blocker, DIDS and analogous chemical compounds (sulfite) suggested specific carrier mediated uptake of both forms. However, DCCD and orthovanadate couldn’t block Se uptake, indicating an energy-independent process. We then tested the hypothesis whether mercury can block both forms of Se uptake or not. Mercury exerted uptake inhibition in both cell types except reduced form (selenite + GSH) of Se in enterocytes. These observations indicate the possibility of at least two different pathways of inorganic Se uptake in enterocytes. However, when both cell types were pre-exposed in combination with mercury and DIDS, the inhibitory effect was higher than DIDS but was comparable with mercury alone. Absence of any synergistic effects in combining exposure raises the possibility of inhibition of anionic transporter by mercury. Overall, our data suggests a passive carrier mediated uptake of inorganic Se in both cell types. 312 THE IRON TRANSPORTER FERROPORTIN CAN ALSO FUNCTION AS A MANGANESE EXPORTER. M. S. Madejczyk and N. Ballatori. Environmental Medicine, University of Rochester School of Medicine, Rochester, NY. Manganese (Mn) is an essential trace element that is utilized in a number of important cellular processes; however, excess Mn can also be quite toxic. Chronic exposure to high levels of Mn leads to neurological damage with psychiatric symptoms as well as disruptions in motor function. The mechanisms by which Mn is transported across cell membranes to reach its target sites are now beginning to be elucidated, although much remains to be learned about these processes, and in particu-
lar about cellular export mechanisms. The present study examined the hypothesis that the iron exporter ferroportin (FPN1) mediates cellular Mn export, using Xenopus laevis oocytes expressing human FPN1. When compared to oocytes expressing only the divalent metal transporter-1 (DMT1), 54 Mn accumulation was lower in oocytes also expressing FPN1. FPN1 expressing oocytes were able to significantly export 54 Mn when compared to control oocytes when injected with 16 μM Mn (27% vs 7.5% respectively, over 4 h at pH 7.4). Export was concentrationdependent and could be partially cis-inhibited by 100 μM Fe, Co, and Ni, but not Rb. In addition, transport ability was lost at pH 5.5, but not at pH 8.5. Incubation in high K media was also able to partially inhibit Mn efflux in FPN1 expressing oocytes. These results indicate that Mn is a substrate for FPN1, and the driving force is both pH and membrane potential-sensitive. 313 CHARACTERIZATION OF ZIP8 AND ZIP14 ZINC/BICARBONATE SYMPORTERS IN XENOPUS OOCYTES: CADMIUM AND ZINC UPTAKE AND INHIBITION BY VARIOUS METALS. M. Gálvez-Peralta, E. B. Hay, H. Li, M. Soleimani, E. Johansson, L. He, B. Wang and D. W. Nebert. University Cincinnati Medical Center, Cincinnati, OH. Cadmium (Cd) is a non-essential metal. Because of increases in cigarette smoking and the industrialization growth, Cd exposure in our environment is increasing dramatically. Chronic exposure to low doses of Cd can cause renal disease and osteomalacia. Cd is classified by IARC as a Category I human lung carcinogen. Cd uptake by mammalian cells uses Ca 2+ channels and SLC11A2 (DMT1). Previous studies from this lab have shown that bicarbonate-dependent Cd uptake is facilitated by SLC39A8 (ZIP8) and SLC39A14 (ZIP14) in mammalian cells. ZIP14 and ZIP8 are divalent cation/HCO3 – symporters, whose endogenous function is primarily zinc uptake. ZIP14A and ZIP14B are distinctly different splice variants of exon 4. In addition to Cd––Hg, Pb, Pt and U are known to cause human renal Fanconi syndrome (renal proximal tubular acidosis). In this work, we inserted mouse ZIP8, ZIP14A and ZIP14B cDNA coding regions into the Xenopus vector pXFRM and performed transcription; capped RNA (cRNA) was microinjected into Xenopus oocytes. Km and Vmax values for Zn and Cd uptake were determined; competitive inhibition of Zn and Cd uptake by the three ZIP symporters was studied for Zn 2+ , Cd 2+ , Hg 2+ , Pb 2+ , Pt 2+ , U 2+ , Co 2+ , Cu 2+ , Ni 2+ , Cs 1+ , Mn 2+ and Fe 2+ . We found that Pt, U, Mn, Fe, Ni and Cs are significant inhibitors of Cd uptake by ZIP8; only high concentrations of Zn, Pt, Co, Mn and Cs inhibited Cd uptake by ZIP14A and ZIP14B. Differences in response were also observed for Zn uptake by the three ZIPs. Little is known about how ZIP14A and ZIP14B organspecific expression is regulated and why the two forms persist evolutionarily, but this study shows they differ in Cd and Zn uptake and competition against different metals. This study also suggests strongly that ZIP8 might play a major role in metal-induced renal Fanconi syndrome.-Supported by NIH grants R01 ES010416, P30 ES06096 (D.W.N.), T32 ES016646 (M.G.-P.), & R01 DK062809 (M.S.) 314 ZIP8 AND ZIP14 ZINC/BICARBONATE SYMPORTERS: THEIR POSSIBLE ROLES DURING INFLAMMATION. Z. Wang 1 , M. Gálvez-Peralta 1 , C. M. Williams 1 , M. Liu 2 , D. L. Knoell 2 and D. W. Nebert 1 . 1 Environmental Health, University of Cincinnati Medical Center, Cincinnati, OH and 2 David Heart and Lung Research Institute, Ohio State University, Columbus, OH. SLC39A8 (ZIP8) and SLC39A14 (ZIP14) are divalent cation/HCO3 – symporters, primarily used for Zn uptake in vertebrate cells. Cd and other nonessential metals enter vertebrate cells by displacing Zn. SLC39A14 has two exons 4, giving celltype-specific expression of ZIP14A and ZIP14B as alternatively-spliced products, whereas SLC39A8 encodes a single product. Because Zn is involved in the host response to inflammatory stress, and inflammation induces hypozincemia, the objective of this project is to determine whether different inflammatory agents are able to induce changes in the expression of these transporters, and if this is organ-specific. C57BL/6J male mice were treated i.p. with TNF (5 μg/kg), IL6 (100 μg/kg) or LPS (5 mg/kg) and 12 tissues were collected at different times for qRT-PCR and Western blot. Because metallothionein and SLC11A2 (DMT1) have been associated with inflammation, their mRNA levels were also measured. To correlate changes in ZIP8, ZIP14A and ZIP14B with inflammation, we also measured TNF, IL6, and IL1B mRNA levels. We found significant differences in the response of each organ, and ZIP mRNAs were induced at different times and patterns: heart showed the most highly TNF-induced ZIP8, ZIP14B mRNA levels; whereas ZIP8 and ZIP14A mRNA reached their highest levels at 8 h, the peak of ZIP14B expression occurred when the levels of ZIP8 and ZIP14A were decreasing (16 h). There was a double peak for interleukins in liver, heart and brain (1st peak at 2-4 h; 2nd peak at 16 h), suggesting an early vs late response; this pattern was also seen for ZIP14B mRNA. ZIP8 and ZIP14A mRNA levels were unchanged in liver or testis. Kidney ZIP8 and ZIP14A mRNA levels were significantly diminished. These observations will help us understand how hypozincemia is regulated in various tissues, following an inflammatory response.-Supported, in part, by NIH grants R01 ES010416 and P30 ES06096 (D.W.N.), T32 ES016646 (M.G.-P.) & R01 HL08698 (D.L.K.) 315 EVALUATION OF MUTAGENICITY, CHROMOSOME BREAKAGE, AND DNA DAMAGE BY PIG-A, MICRONUCLEUS AND COMET ASSAYS IN 28-DAY REPEATED DOSE TOXICITY STUDIES. J. Shi 1 , M. Paranjpe 1 , S. W. Bruce 1 , T. Kelley 1 , S. Springer 1 , J. Sly 1 , M. Klug 1 , M. Arevaro 1 , S. Atta-Safoh 1 , F. Debelie 1 , L. Krsmanovic 1 , P. Sareen 1 and S. Dertinger 2 . 1 BioReliance Corporation, Rockville, MD and 2 Litron Laboratories, Rochester, NY. Integration of multiple in vivo genotoxicity endpoints into repeat dose general toxicity studies not only allows evaluating genotoxic potential of the test compounds with several endpoints which detect different genotoxic mode of action (MOA) in different organs, but also has the potential to reduce animal use. Here, we evaluated two genotoxic compounds, 7,12-dimethylbenz(a)anthracene (DMBA) and diethylnitrosamine (DEN) for Pig-a gene mutation and chromosomal damage in peripheral blood, and primary DNA damage in liver and blood cells in Sprague Dawley rats treated daily for 28 days. An additional treatment was performed 3 hours prior to necropsy on Study Day 29 for DNA damage evaluation. Peripheral blood samples obtained on Study Days -1, 15 and 29 were analyzed by flow cytometry to determine the frequencies of CD59-negative erythrocytes and reticulocytes (indicative of Pig-a gene mutation). Frequencies of micronucleated reticulocytes (%MN-RETs) were determined in peripheral blood obtained on Study Days 4 and 29 by flow cytometry. As a result, DMBA induced dose-dependent increases of CD59-negative erythrocytes/reticulocytes and MN-RETs, but no significant increase in DNA damage in liver cells when tested up to 10 mg/kg/day, which appears to be below the maximum tolerated dose. When tested up to 200 mg/kg/day in a follow up acute study, DMBA was determined positive in the liver Comet assay. On the other hand, DEN produced negative results in both the Pig-a mutation assay and the MN assay, and evaluation of Comet slides are still in progress. The different responses observed in the three genotoxicity endpoints induced by DMBA or DEN provided a characterization of the genotoxic MOA, target organs and a comparison of assay sensitivity under the experimental conditions. 316 A NOVEL HIGH-THROUGHPUT IN VITRO MNT PROFILING ASSAY FOR SUSPENSION CELLS. S. Kirchner, M. Prummer, S. Marget-Müller, J. Muller, C. McGinnis, K. Kolaja, R. Werder, K. Christensen, S. Zoffmann, T. Enderle, R. Rietmann, D. Vögelin, P. Iaiza, C. Fattinger and T. Weiser. F. Hoffmann-La Roche Ltd., CH- 4070 Basel, Switzerland. The in vitro micronucleus assay is well established as an early tool to evaluate the aneugenic and/or clastogenic activity of potentially new drug candidates. The recent acceptance of OECD TG487 by regulatory agencies positions the in vitro MNT as an alternative for both the GLP in vitro chromosomal aberration assay and the L5178Y Mouse Lymphoma assay. This allows for the first time to use the same assay and cell system throughout the different stages of testing in the drug development process with its specific needs. So far standard suspension cell lines used for in vitro micronucleus evaluation such as L5178Y and TK6 were only accessible to true high throughput applications by means of flow cytometry not allowing for analysis on a single cell level. We are presenting here a novel and universal approach to prepare arrays of non-adherent cells from 96-well plates for automated microscopy and micronucleus evaluation to fill this gap. For image segmentation and object classification we co-developed an adaptive and iterative algorithm for L5178Y cells using Definiens Cognition Network Technology and non-parametric statistical methods were applied to classify the micronucleation potential. To validate the assay protocol we compared the results obtained between the high throughput 96-well plate method and a regulatory like in vitro micronucleus screening assay for selected reference and 224 in house compounds using L5178Y cells. Based on these experiences, this high throughput in vitro MNT approach will be compared and contrasted within the context of supporting the early development of drug candidates. In summary, these developments open up new possibilities for aligning the clastogenicity/aneugenicity assessment throughout the drug development process from HT approaches to regulatory like screening and regulatory testing when using suspension cells. In addition this development might also have the potential to make human primary lymphocytes more accessible to higher throughput applications. SOT 2011 ANNUAL MEETING 67
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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
Page 19 and 20: additional compound showed agreemen
Page 21 and 22: 82 COMPARISON OF 3H-THYMIDINE INCOR
Page 23 and 24: irritants. While in practice these
Page 25 and 26: alleles are especially vulnerable t
Page 27 and 28: 109 CD4+ T CELL INTRINSIC TNF RECEP
Page 29 and 30: 118 TO STUDY THE SIGNAL TRANSDUCTIO
Page 31 and 32: PAHs, such as dioxins, are prevalen
Page 33 and 34: containing substituents and/or hydr
Page 35 and 36: 146 COMPUTATIONAL MODELING FOR QT P
Page 37 and 38: suggest that the combination of too
Page 39 and 40: 164 TRANSLOCATOR PROTEIN (18 KDA) (
Page 41 and 42: function as a metal binding protein
Page 43 and 44: laboratory has demonstrated that NR
Page 45 and 46: known. The aim of this study was to
Page 47 and 48: from 5 to 28 days in duration) in e
Page 49 and 50: positive cells, caspase-3 activatio
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Page 57 and 58: 247 CO-CARCINOGENESIS OF N, N- DIET
Page 59 and 60: sponds to the endosomal dsRNA that
Page 61 and 62: ODD in both WT (maximum 177% of con
Page 63 and 64: Lastly, using p53siRNA cells, p53 w
Page 65 and 66: its receptor Mpl to exert its funct
Page 67 and 68: 294 LOW LEVEL OF LEAD CAN INDUCE PH
Page 69: lunar surface presented potential h
Page 73 and 74: DNA in the kidney medulla, grandula
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Page 81 and 82: 358 CHARACTERIZATION OF GENOME-WIDE
Page 83 and 84: RNAi were also performed to identif
Page 85 and 86: 376 A FUNCTIONAL CROSSTALK BETWEEN
Page 87 and 88: UGT1A gene induction, while this re
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Page 91 and 92: and cytotoxic effects; however, its
Page 93 and 94: histone deacetylase that is necessa
Page 95 and 96: ment. Paradoxically, buthionine sul
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Page 99 and 100: 442 GENE EXPRESSION AND MORPHOLOGIC
Page 101 and 102: 451 INHIBITION OF THE MITOCHONDRIAL
Page 103 and 104: 460 SULFORAPHANE PREVENTS ACETAMINO
Page 105 and 106: drophilic/lipophilic balance. Other
Page 107 and 108: pharmacokinetic and toxicological p
Page 109 and 110: 489 USE OF ‘OMICS DATA TO IMPROVE
Page 111 and 112: 498 APPLICATION OF AGE-SPECIFIC ADJ
Page 113 and 114: 507 A DOSE VOLUME TOLERABILITY STUD
Page 115 and 116: involved the use of an acute inflam
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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
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Results: MC was variable within and
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UtSMCs. Phosphorylation of FoxO1 wa
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nonpregnant and pregnant diabetic m
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1089 PFOA-INDUCED LIVER EFFECTS IN
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events in the liver. AZD9056 was ev
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The peppermint oil caused a concent
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OA did not affect food consumption.
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1126 PERSISTENT DEVELOPMENTAL ARYLH
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1135 BACH2 BINDING TO Prdm1 AS A ME
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The purpose of this project was to
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one marrow. Since Chk1 is an attrac
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1163 THE MRNA AND MIRNA PROFILE OF
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have now compared the IC50 values b
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1181 ELUCIDATION OF FACTORS DETERMI
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enced by pre-exposure to cigarette
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if abnormal PF was associated with
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weight (P=0.016) and small for gest
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portant cause of death, compared to
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posure groups. However, the differe
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Naphthalene is routinely analyzed i
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1245 SEASONAL CHARACTERIZATION OF H
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1255 URINARY T, T MUCONIC ACID LEVE
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modating a reliable data evaluation
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enzoquinone generate ROS and arylat
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teins (e.g. C3, 4, and 5, APOB, VDB
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1293 TRANSFORMING GROWTH FACTOR BET
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mation was decreased to the same le
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1312 EVALUATION OF THE SENSITIVITY
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luted OFR and CRL. Culture media ex
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urinary TCPy levels, blood and brai
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activity. The dose-response curves
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mice, each with 4 dose groups. One
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exposure to both ATR and DACT has a
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third tetratricopeptide repeats (TP
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7d. 28d after TMT injury there was
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subunits. Each cell type was treate
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1394 COMPARATIVE EFFECTS OF METHYLM
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1403 GENOTOXICITY AND PRE-NEOPLASTI
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vated only in high-dose-treated ani
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1421 DOSE-RESPONSE OF NAPHTHALENE-I
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cisplatin; 1.2-, 1.9- and 2.9-fold
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Day 11 and started to recover on Da
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1448 DEVELOPMENT OF A METHOD FOR QU
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1457 GLOBAL GENE PROFILING REVEALS
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cluding mouse and human macrophage,
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model of lung inflammation and host
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1484 NANOTOXICOLOGY AND NANOHEALTH
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throughput in vitro approach was us
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1502 IMMUNOLOGICAL ASPECTS OF AN AN
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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
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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