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684 1, 3-DIBROMOPROPANE UP-REGULATES INDUCIBLE NITRIC OXIDE SYNTHASE EXPRESSION VIA NF-KB ACTIVATION IN MACROPHAGES. J. Yang 1 , E. Han 1 , J. Im 1 , K. Lee 2 , T. Jeong 3 and H. Jeong 1 . 1 Pharmacy, Chungnam National University, Daejeon, Republic of Korea, 2 Pharmacy, Chonnam National University, Gwangju, Republic of Korea and 3 Pharmacy, Yeungnam University, Kyungsan, Republic of Korea. Bromopropane has been used in the workplace as an alternative to ozone-depleting solvents. In this study we investigated the effect of 1,3-dibromopropane (DBP) on nitric oxide (NO) and proinflammatory cytokines production in mouse macrophages. DBP induced the production of NO and proinflammatory cytokines such as IL-1, IL-6 and TNF- and expression levels of these genes in a dose-dependent manner. The NF-κB sites were identified in the promoter of the inducible NO synthases (iNOS) and proinflammatory cytokines genes. Transient transfection revealed that NF-kB mediated the DBP-induced increase in the iNOS and proinflammatory cytokines expression levels. This demonstrates that DBP stimulates macrophage activation via NF-kB transactivation. These results suggest that DBP has the potential to be inflammatory and that is has previously unrecognized immunomodulating activity. 685 SYNERGISM OF LEPTIN SIGNALING AND POST TRANSLATIONAL PROTEIN OXIDATION IN BROMODICHLOROMETHANE EXPOSURE IS KEY TO THE DEVELOPMENT OF STEATOHEPATITIS OF OBESITY. S. Chatterjee, J. Clark, M. Kadiiska and R. P. Mason. Laboratory of Toxicology and Pharmacology, NIEHS, Research Triangle Park, NC. Disinfection byproducts like bromodichloromethane (BDCM) at a dose of at least 5 mMoles/kg is known to be hepatotoxic with necroinflammatory lesions. Although direct exposure to high doses of BDCM is rare, low exposures from the environment are not uncommon. These doses are well tolerated by normal healthy individuals but can be potential risk factors for inflammatory liver injury like steatohepatitis in obese subjects. We tested the hypothesis that metabolic oxidative stress arising from such low exposures in obese subjects synergise with high leptin levels and lead to exacerbation of steatohepatitis through lipid peroxidation, protein oxidations and innate immunity. Results indicated that BDCM exposure ( 2mMoles/kg) caused significantly increased lipid peroxidation in hepatocytes of diet-induced obese (DIO) and leptin-k/o mice at 6h. There was also a significant increase in protein radical adducts and post-translational tyrosine nitration in sinusoidal cells including Kupffer cells at 24 hrs when compared to leptin-k/o or lean control mice at 24h. Confocal microscopy studies and liver histopathology from wild-type DIO obese mice showed perivenular aggregation of Kupffer cells and marked necroinflammation. The role of CYP2E1, one of the enzymes of the cytoctochrome P450 family in BDCM bioactivation, and NADPH oxidase were also confirmed using specific inhibitors for these enzymes. Results also showed that Kupffer cells from DIO mice exposed to BDCM had enhanced TNF-alpha release when compared to corresponding lean controls and leptin-knockout mice. Kupffer cells co-incubated either with 4-hydroxy Tempol, a superoxide dismutase mimetic, or higher concentrations of the spin trap DMPO (100mM) significantly reduced macrophage activation. Taken together, our data for the first time suggest that BDCM bioactivation from the environmental sources and leptin generates an inflammatory cascade and free radical damage in obese individuals. 686 EFFECT OF LEAD EXPOSURE ON THE MACROPHAGES ACTIVATION THROUGH TLR4. A. L. Luna 1, 2 , N. A. Torres-Aviles 1 , L. C. Acosta-Saavedra 1 , E. K. Silbergeld 3 and E. S. Calderon-Aranda 1 . 1 Department Toxicologia, Cinvestav, Mexico, Mexico, 2 Biomedicina Molecular, ENMH-IPN, Mexico, Mexico and 3 BSPH, Johns Hopkins University, Baltimore, MD. Lead is a metal that increases susceptibility to infection by pathogens such as Escherichia coli and Staphylococcus aureus. Macrophages recognized PAMP’s (patterns of molecules associated with pathogens) through TLR (Toll Like Receptors). The binding of PAMP’s by TLR induce macrophages activation, production of bactericidal species like nitric oxide (NO -), and the secretion of inflammatory cytokines. The aim was to study the effect of environmentally relevant non-cytotoxic lead concentrations, on the activation of macrophages through TLR4, using two lipopolysaccharides (LPS) which are derived from different pathogens to determine if the effect of Pb is dependent of the pathogen. Methods: murine macrophages J774A.1 were exposed to lead acetate (AcPb) (range from 0.005 to 250μg/dL) and activated with lipopolysaccharide (LPS) from Salmonella typhimurium or Escherichia coli under two schemes: a) Pre-exposure to AcPb and subsequent acti- 148 SOT 2011 ANNUAL MEETING vation, b) Co-exposure to AcPb and LPS. Viability was assessed by the MTT method, and macrophage activation by NO - production (Griess method), and secretion of IL-1β, IL-6 and TNF-α (ELISA). Results: 0.05 to 25μg/dL of AcPb do not affect viability and were to all assays. The pre-exposure to AcPb decreases NO - induced with E. coli but does not with Salmonella; in the co-exposure AcPb increases the NO - induced by E. coli but does not in the NO - induced with Salmonella. The pre-exposure to AcPb increases IL-1β induced with both LPS, decreases IL-6 induced with E. coli but does not IL-6 induced with Salmonella. AcPb decreases TNF-α induced with E. coli and increases this cytokine only at 5μg/dL of AcPb. In co-exposure scheme AcPb decreases IL-1β induced with both LPS, decreases IL-6 and TNF-α with both LPS. The results suggest that AcPb affect macrophage activation dependent of PAMP’s origin and probably alteration of TLR4 pathway at extracellular level. 687 CONTINUOUS AND LOW-DOSE EXPOSURE TO ASBESTOS ENHANCES TGF-β1 PRODUCTION IN A HUMAN ADULT T CELL LEUKEMIA VIRUS- IMMORTALIZED T CELL LINE, MT-2. T. Otsuki, M. Maeda, N. Kumagai, N. Miyahara, M. Katoh, S. Yamamoto, T. Hatayama and Y. Nishimura. Hygiene, Kawasaki Medical School, Kurashiki, Japan. Asbestos exposure not only causes pulmonary fibrosis, but also induces various tumors such as lung cancer and malignant mesothelioma. To elucidate the immunological alteration in asbestos-related tumors, an asbestos-induced apoptosis-resistant subline (MT-2Rst) was established from a human adult T cell leukemia virus-immortalized T cell line (MT-2Org) by long-term, low-level exposure to asbestos chrysotile-B (CB). The mechanisms of acquisition of resistance against the asbestos-induced apptosis are activation of Src-family kinases, overexpression and secretion of IL-10, phosphorylation of STAT3, and activation of Bcl-2. In this study, transforming growth factor-beta1 (TGF-β1) knockdown using lentiviral vector-mediated RNA interference showed that MT-2Rst cells secrete increased level of TGF-β1 as well as IL-10, and acquire resistance to TGF-β1-mediated growth inhibition via the deficiency in TGF-β1/SMAD signaling. However, Annexin V assay indicated that TGF-β1 resistance in MT-2Rst cells were not directly involved in the acquisition of resistance to apoptosis that is triggered by CB exposure. Alternatively, we showed that TGF-β1 production in MT-2Org cells is mediated through the activation of the mitogen-activated protein kinases (MAPKs), ERK1/2 and p38, by exposure to CB. Furthermore, TGF-β1-knockdown cells and treatment with MAPKs inhibitors revealed that MT-2Rst cells secrete high level of TGF-β1 via mainly phospholylation of p38. Taken together, long-term, low-level exposure to CB on MT-2Org cells induce regulatory T cells-like phenotype, suggesting that chronic exposure to asbestos lead to a state of immune suppression. 688 EFFECT OF VIBRIO VULNIFICUS LIPOPOLYSACCHARIDE (LPS) ON RAT BRAIN MICROGLIA: CYTOKINE AND CHEMOKINE EXPRESSION PROFILING BY ANTIBODY ARRAY TECHNOLOGY. L. D. Ottenhoff 1 , N. Patel 1 , M. L. Hall 1 , K. B. Glaser 2, 1 , P. B. Jacobson 2 , D. Rowley 3 , C. De Castro 4 , A. Molinaro 4 and A. M. Mayer 1 . 1 Pharmacology, Midwestern University, Downers Grove, IL, 2 Abbott Laboratories, Chicago, IL, 3 Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, RI and 4 Chimica Organica e Biochimica, Università di Napoli Federico II, Naples, Italy. We have reported that Vibrio vulnificus LPS (VvLPS)-stimulated rat neonatal brain microglia (BMG) release of TNF-α, TXB 2 , O 2 - and MMP-9 (The Faseb Journal 21(5): A 404, 2007), and interleukin-1 α (IL-1α), IL-6, and MIP-2/CXCL2 (The Toxicologist, 108 (S1): 12, 2009). The purpose of this investigation was to determine whether additional cytokines and chemokines were present in conditioned media of BMG cultures treated with VvLPS, using the RayBio® biotin label-based rat antibody array technology (RayBiotech, Inc., Norcross, GA). VvLPS was isolated from VvLPS strain MO6-24/O by hot phenol/water extraction. Neonatal rat BMG were treated in vitro with (1 x 10 3 ng/mL) VvLPS for 17 h. The study revealed the presence of several upregulated cytokines and chemokines in conditioned media (greater than two-fold increase vs. unstimulated BMG ), namely: IL- 6 (10), MCP-1/CCL2 (6.5), MIP-1α /CCL3 (5.6), BDNF(3.1), and Cinc-2α/β/CXCL3 (1.3); and one downregulated cytokine (greater than two-fold decrease vs. unstimulated BMG ): IL-1α ( -2.8 ). We conclude that the RayBio® protein array technology has enabled detection of additional cytokines and chemokines in conditioned media from 17 h in vitro VvLPS-treated BMG. Confirmation of RayBio® protein array results with chemokine and cytokine-specific ELISAs is currently ongoing in our laboratory. Our results provide further insight into proinflammatory mediators released by VvLPS–treated BMG that may contribute to self-injury and/or neuronal toxicity. Financial support by Midwestern University is acknowledged.
689 ENHANCED SUPPRESSIVE FUNCTION ON REGULATORY T CELL-LIKE CELL LINE, MT-2, BY CONTINUOUS EXPOSURE TO ASBESTOS. M. Maeda 1 , Y. Chen 1 , Y. Nishimura 1 , N. Kumagai 1 , H. Hayashi 1 , Y. Miura 2 and T. Otsuki 1 . 1 Hygiene, Kawasaki Medical School, Kurashiki, Okayama, Japan and 2 Molecular Genetics, Kyushu University, Fukuoka, Japan. [Introduction] Chronic exposure to asbestos occurs malignant mesothelioma. As this disease has a long incubation period, CD4 + CD25 + regulatory T (Treg) cellsmediated anti-tumor immune response may be impaired. To reveal whether Treg cells exposed to asbestos attenuate an anti-tumor immune function in malignant mesothelioma patients, six chrysotile-induced apoptosis-resistant sublines (MT- 2Rsts) were established by long-term (more than 8 months) and low-level (10 μg/ml) exposure to chrysotile-A or -B from the HTLV-1-immortalized human Tcell line MT-2 (MT-2Org) having a Treg-like suppressive function, and their suppressive functions were estimated by mixed lymphocyte reaction (MLR). [Methods] The regulatory function in an allogeneic MLR was determined using [ 3 H]-Thymidine incorporation. Expression of Treg markers (Foxp3, CTLA-4 and GITR) was analyzed by flow cytometry. The mechanisms of the suppressive function were clarified in MT-2Rst using a CFSE assay. Involvement of immunosuppressive cytokines IL-10 and TGF-β1 in suppressive function was investigated using an shRNA knockdown system. [Results and Discussions] Five MT-2Rst cell lines suppressed proliferation of CD4 + CD25 - responder T-cells (Tresp) upon stimulation with irradiated allogeneic PBMCs more strongly than MT-2Org. The results of flow cytometry showed that MT-2Org and MT-2Rsts cells expressed high levels of Foxp3 and GITR. When Tresp were stimulated with coated anti-CD3 antibody and autologous induced-dendritic cells, the proliferation was suppressed by MT-2Rst more strongly than MT-2Org. Furthermore, shRNA knockdown showed that IL-10 and TGF-β1 produced from MT-2Rst suppressed the proliferation of Tresp. In conclusion, these findings revealed that chronic exposure to asbestos enhanced the suppressive function through cell contact-dependent mechanisms and soluble factors in MT-2Rst, suggesting that asbestos exposure enhances Treg suppressive function and lead to a decrease in anti-tumor immune function. 690 HISTONE DEACETYLASES PLAY A CRITICAL ROLE IN REGULATING IFNα-MEDIATED ANTI-HCV GENE EXPRESSION. S. Mathews 1 , S. Joshi-Barve 1 , C. McClain 1, 2 and S. Barve 1 . 1 Department of Medicine/GI, University of Louisville, Louisville, KY and 2 Robley Rex Veterans Administration Medical Center, Louisville, KY. Hepatitis C virus (HCV) is a major cause of chronic liver disease and is a huge burden on the United States healthcare system. The FDA-approved standard of care is pegylated interferon-alpha (IFNα) in combination with ribavirin; however up to 50% of patients do not respond to this therapy. Understanding the regulatory mechanisms that play an essential role in the expression of IFNα anti-HCV genes may lead to the development of therapeutic options that increase the effectiveness of IFNα. The present work was carried out to examine the potential role of histone deacetylases (HDACs) in the regulation of IFNα-stimulated anti-HCV genes. Two class I HDAC inhibitors (HDACi), trichostatin A (TSA) and suberic bishydroxamate (SBHA) were used to treat human hepatoma cells (Huh7 and HCVR; Huh7 stably transfected with an HCV replicon) or primary human hepatocytes prior to stimulation with IFNα. HDACi pretreatment inhibited induction of several IFN-mediated antiviral genes, as analyzed by real-time PCR. Importantly, this inhibition corresponded to decreased activation of the interferon stimulated response element (ISRE) found in the promoters of IFNα antiviral genes. Additionally, HDACi led to retention of phospho-STAT1 in the cytoplasm, potentially due to altered acetylation of STAT1, and corresponded to impaired expression of antiviral proteins. Immunoprecipitation analysis using lysates from IFNα-stimulated cells identified HDAC1 binding to STAT1 in the nucleus and this interaction was inhibited by HDACi. Since HDACi block the actions of class I HDACs, siRNA was used to specifically identify HDAC1 and HDAC3 as critical regulators of IFNα antiviral signaling. Taken together, the data from these experiments reveal a unique requirement for HDACs 1 and 3 in regulating IFNα-mediated anti-HCV gene expression in hepatocytes. 691 ZIRAM INDUCES APOPTOSIS IN HUMAN IMMUNE CELLS. Q. Li, M. Kobayashi and T. Kawada. Nippon Medical School, Tokyo, Japan. Background: Ziram as a dithiocarbamate fungicide is widely used throughout the world in agriculture and as an accelerating agent is used in latex production. It has been reported that ziram shows immunotoxicity. Purpose: To explore the mechanism of ziram-induced immunotoxicity, we investigated ziram-induced apoptosis/necrosis and its underlying mechanism in human immune cells. Materials and Methods: U937, a human monocyte like cell line and NK-92MI, a human NK cell line, were treated with ziram at 0.0312-2 μM for 2-24 h at 37°C in a 5% CO2 incubator. Apoptosis/necrosis induced by ziram was determined by analysis of FITC-Annexin-V/PI staining and the intracellular level of active caspase-3 by flow cytometry and DNA fragmentation analysis (1-3). Mitochondrial cytochrome c release in U937 cells induced by ziram was also determined by flow cytometry (3). Results: We found that ziram induced apoptosis/necrosis in both U937 and NK- 92MI cells in a dose- and time-dependent manner, as shown by FITC-Annexin- V/PI staining. DNA fragmentation was detected when U937 cells were treated with 0.5, 1 or 2 μM ziram for 24 h. Ziram also induced an increase of intracellular active caspase-3 in U937 and NK-92MI cells in a dose-dependent manner, and a caspase- 3 inhibitor, Z-DEVD-FMK, significantly inhibited the ziram-induced apoptosis. Moreover, it was found that ziram induced mitochondrial cytochrome c release in U937 cells. Conclusions: These findings indicate that ziram can induce apoptosis/necrosis in both U937 and NK-92MI cells, and this effect is partially mediated by activation of intracellular caspase-3 and mitochondrial cytochrome c release. From this perspective, we speculate that ziram-induced immunotoxicity may be mediated by apoptosis in immune cells. Acknowledgements: This work was supported by a grant from the Ministry of Education, Culture, Sports, Science and Technology (No.22590554). References: 1. Li Q, et al. Toxicology 239:89-95, 2007. 2. Li Q, et al. Toxicology 255:53-57, 2009. 3. Li Q, et al. Arch Toxicol (in press) 692 ENHANCEMENT OF HUMORAL IMMUNITY BY THE ENDOCRINE DISRUPTER PROPANIL IS NOT ALTERED BY NEONATAL ANDROGEN TREATMENT. R. Schafer 1 , S. Hileman 2 , R. Goodman 2 and I. Holaskova 1 . 1 Microbiology, Immunology, and Cell Biology, West Virginia University, Morgantown, WV and 2 Physiology and Pharmacology, West Virginia University, Morgantown, WV. Studies in our laboratory demonstrated that the pesticide propanil enhances the immune response to a vaccine that is dependent on the gonads in females but is independent of the gonads in males. This effect was independent of estrogen, progesterone and testosterone. The dramatically different response of gonadectomized male and female mice to propanil raised the possibility that the immune response is sexually differentiated and accounts for the sexually-dimorphic effect of propanil in adults. We hypothesized that androgen treatment of neonatal female mice would normalize the enhanced antibody response after propanil exposure in ovariectomized (OVX) adult females. Neonatal C57Bl/6 pups were treated subcutaneously with testosterone propionate (TP, 400 μg in corn oil) or corn oil within 24 hours of birth. Efficacy of TP treatment in females was determined by vaginal smears and uterine weight. At 6 weeks of age female mice were OVX or sham OVX. Mice were vaccinated at 10 weeks of age with heat-killed Streptococcus pneumoniae and treated with propanil or vehicle. One week later the spleens were collected and the antibody response to the vaccine was determined by ELISPOT assay. Testosterone treatment resulted in abrogation of the estrous cycle. Propanil significantly increased IgM and IgG antibody producing cells in males treated with TP at birth. In females given TP at birth, propanil significantly increased IgM, IgG, and IgG3 responses. Ovariectomy abrogated the increase demonstrating that the enhanced immune response after propanil exposure is still dependent on the ovaries in TP treated females. Thus, neonatal androgen treatment produced the expected effects on the reproductive system but did not alter the normal immune response to S. pneumoniae vaccine in adults. This indicates that the immune system of females was not masculinized during the neonatal time period and ovarian function is crucial for the enhanced response. 693 ASBESTOS EXPOSURE CAUSES DECREASE IN PRODUCTION OF CYTOKINES RELATED TO NK CELL ACTIVATION. Y. Nishimura, N. Kumagai, M. Maeda, H. Hayashi and T. Otsuki. Hygiene, Kawasaki Medical School, Kurashiki, Japan. Recently, we reported that peripheral blood NK cells in patients with malignant mesothelioma (MM) showed low cytotoxicity with decrease in NKp46, one of receptors utilized to recognize targets and transduce activation signal, which also decreased in NK cells included in PBMCs cultured with chrysotile B (CB) asbestos. Additionally, purified NK cells showed an increase in NKp46 when co-cultured SOT 2011 ANNUAL MEETING 149
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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
Page 101 and 102: 451 INHIBITION OF THE MITOCHONDRIAL
Page 103 and 104: 460 SULFORAPHANE PREVENTS ACETAMINO
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Page 109 and 110: 489 USE OF ‘OMICS DATA TO IMPROVE
Page 111 and 112: 498 APPLICATION OF AGE-SPECIFIC ADJ
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Page 115 and 116: involved the use of an acute inflam
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Page 121 and 122: 545 BEHAVIORAL EFFECTS OF REPIN IN
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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
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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