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examine its effects on the development of autoimmunity. Results: 4 out of 8 rats treated with penicillamine developed autoimmunity. The percentage of CD4+IL- 17+ cell population was found significantly increased in the animals that developed autoimmunity (1.65±0.46%), compared with control and non-sick groups (0.27±0.08% and 0.29±0.09%, respectively). Surprisingly, all the animals that had been treated with RA and penicillamine developed autoimmunity and it was more severe. Conclusions: Our data provided additional evidence in support of Th17 cell involvement in penicillamine-induced autoimmunity. However, further studies should be carried out to reveal the effects of RA on the in vivo development of Th17 cells and penicillamine-induced autoimmunity. This work was supported by Canadian Institutes of Health Research. 1507 INDOLES MITIGATE THE DEVELOPMENT OF EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS BY ACTIVATION AHR AND ER, RECIPROCAL INDUCTION OF REGULATORY T CELLS AND TH17 CELLS, AND INDUCTION OF APOPTOSIS. M. Rouse, M. Nagarkatti and P. Nagarkatti. University of South Carolina, Columbia, SC. Indigo is one of the oldest dyes known to mankind and produced by fermentation of certain plants. More importantly, indigo has been used in traditional Chinese medicine. Diindolylmethane (DIM) and its precursor, Indole-3-carbinol (I3C), for example, are two cruciferous indoles that are used as dietary supplements. Both DIM and I3C have been shown to act as AhR ligands similar to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). In the current study, we hypothesized that DIM and I3C may regulate the immune response through the activation of the AhR and ER, similar to another dietary supplement, resveratrol. We induced experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis (MS) by injecting MOG peptide into C57BL/6 mice along with complete Freund’s adjuvant and pertussis toxin. The results demonstrated that use of DIM and I3C in EAE mice was effective in not only delaying the clinical symptoms of paralysis, but also curtailed the overall severity. We observed that treatment with DIM and I3C caused reciprocal regulation of Tregs and Th17 cells. In addition, DIM and I3C treated EAE mice revealed a dramatic decrease in CD4+ T-cells in the brain, while preserving resident microglial cells. In a H3-incorporation assay, DIM and I3C demonstrated a pronounced ability to inhibit ConA activated T-cell proliferation. Cell cycle analysis further suggested that treatment of these indoles can lead to increased apoptosis and G0/G1 arrest. Together, these studies demonstrate that indoles act through multiple pathways to suppress EAE development.(Supported in part by NIH grants R01ES09098, P01AT003961, R01ES019313). 1508 TNF RECEPTOR 2 (TNFR2)-DEFICIENT MYELIN OLIGODENDROCYTE GLYCOPROTEIN (MOG)- SPECIFIC T CELL RECEPTOR (TCR) TRANSGENIC MICE DEVELOP SPONTANEOUS AUTOIMMUNITY. P. G. Miller 3 , E. N. Sellers 3 , R. S. Schondelmeyer 3 , M.B.Bonn 4 , J.K.Dey 4 ,J. A. Cascio 2 , C. Franklin 2 , H. Braley-Mullen 2 , N. H. Ruddle 5 and S. C. McKarns 1, 2 . 1 Surgery, University of Missouri, Columbia, MO, 2 Molecular Microbiology & Immunology, University of Missouri, Columbia, MO, 3 Biochemistry, University of Missouri, Columbia, MO, 4 Biological Sciences, University of Missouri, Columbia, MO and 5 Biological & Biomedical Sciences, Yale University, New Haven, CT. Multiple sclerosis (MS) is an autoimmune disease characterized by inflammatory infiltration and demyelination in the central nervous system (CNS). There is no cure. Genetic and environmental factors have been implicated in a loss of self-tolerance in genetically susceptible individuals. Tumor necrosis factor-alpha (TNF) has dual pro-inflammatory and immunoregulatory properties with key physiological and pathological regulatory roles. TNF antagonists treat several autoimmune diseases including rheumatoid arthritis and Crohn’s disease. Yet, despite clinical evidence implicating that TNF contributes to MS, anti-TNF therapies unexpectedly worsen MS. Given the “double-edge sword” potential of TNF to differentially regulate both neuro-protective and destructive responses, the inability of TNF antagonists to treat MS may represent variable TNF signaling. We have shown that TNFR2, but not TNFR1,-deficiency increases susceptibility to MOG-induced EAE. The objective of this research is to define the role of TNFR2 signaling on cytokine production and neuronal protection in CNS autoimmunity. Here, we report a high incidence of lethal spontaneous neurodegenerative autoimmunity in female C57BL/6 TNFR2-deficient, but not TNF-deficient, mice bred onto the MOGspecific TCR transgenic (2D2) background. We correlate disease incidence in TNFR2.KO mice with infiltration of MOG-specific CD4+ T effector cells into the CNS and decreased suppression of cytokines by FoxP3+ CD4+ T regulatory cells. Our data demonstrate that TNFR2 is essential for the function of T regulatory cells and that CNS autoimmune disease varies with TNF signaling. These results identify selective activation of TNFR2 as a potential effective drug target for MS. 324 SOT 2011 ANNUAL MEETING 1509 ANTI-MESOTHELIAL CELL AUTOANTIBODIES ASSOCIATED WITH ASBESTOS EXPOSURE AND PLEURAL DISEASE. L. S. Marchand2 , J. C. Pfau1 , S. Sophie1 and E. A. Putnam3 . 1Biological Sciences, Idaho State University, Pocatello, ID, 2School of Medicine, University of Washington, Seattle, WA and 3Biomedical & Pharmaceutical Sciences, University of Montana, Missoula, MT. Despite data linking asbestos exposure with production of autoantibodies, questions remain about the role of the autoantibodies in subsequent disease. Residents of Libby, Montana have experienced significant exposure to amphibole asbestos due to the mining of asbestos-contaminated vermiculite near the community over several decades. This population predominantly exhibits pleural disease, and an autoimmune-like disorder that has yet to be well defined. This study investigated the relationship between autoimmunity and asbestos related disease (ARD). Serum samples of subjects from Libby were evaluated for anti-nuclear antibodies (ANA), and for anti-mesothelial antibody (AMA) using cell based ELISA testing. In accord with previous studies, 62% of the Libby samples were ANA positive, a frequency much higher than expected for a typical healthy population. The odds of having pulmonary disease was nearly four times greater for individuals positive for ANA compared with individuals negative for ANA. The Libby population also exhibited a significantly higher frequency of AMA than the control group. A total of 23 Libby subjects had significantly high AMA levels and were established as AMA positive. Of these subjects nearly 75% (17 subjects) had pleural disease. Therefore, the odds of having pleural disease was 4.72 times greater for individuals with positive AMA compared to subjects without positive AMA. In contrast there was no significant relationship between AMA positivity and interstitial disease. This raises the possibility that AMAs are contributing to the ARD in these patients. Additional research is needed to further establish the relationship, but an association between AMA and clinical disease progression might lead to an excellent target for therapeutic intervention, or mechanisms to better define and monitor disease in this patient population. 1510 INVOLVEMENT OF OXIDATIVE STRESS IN TRICHLOROETHENE-MEDIATED AUTOIMMUNITY: DOSE- AND TIME-RESPONSE STUDY. G. Wang, J. Wang, X. Fan and M. Khan. Pathology, University of Texas Medical Branch, Galveston, TX. Trichloroethene (TCE), a common environmental contaminant, is known to induce autoimmunity. Previous studies in our laboratory showed increased oxidative stress in TCE-mediated autoimmunity. To further establish the role of oxidative stress and to investigate the mechanisms of TCE-mediated autoimmunity, doseand time- response studies were conducted in female MRL+/+ mice by treating them with TCE via drinking water at doses of 0.5, 1.0 or 2.0 mg/ml for 12, 24 or 36 weeks. TCE exposure led to dose-dependent increases in anti-malondialdehyde (MDA)- and anti-4-hydroxynonenal (HNE)-protein adduct antibodies in the sera at 24 and 36 weeks, but the increases were greater at 36 weeks. However, no changes in these antibodies were observed at 12 weeks. The increases in these antibodies were associated with significant elevation in serum anti-nuclear- and antissDNA-antibodies at 24 weeks and, to a greater extent, at 36 weeks, suggesting an association between TCE-induced lipid peroxidation and induction of autoimmunity. Moreover, splenocytes from mice treated with TCE for 24 weeks secreted significantly higher levels of IL-17 and IL-21 than did splenocytes from controls following 72 h stimulation with MDA-mouse serum albumin (MDA-MSA) or HNE-MSA adducts, and the increased release of cytokines showed a dose-dependent response. Interestingly, the cytokine release was even greater in mice treated with TCE for 36 weeks. This study not only provides an evidence for the existence of a dose-and time-dependent association among TCE exposure, oxidative stress and induction of autoimmunity, but also suggests that MDA- and/or HNE-modified proteins act as an immunologic trigger and activate Th17 cells, thus contributing to an autoimmune response. Supported by NIH ES016302. 1511 EFFECTS OF LIBBY AMPHIBOLE ASBESTOS EXPOSURE ON TWO RAT MODELS OF RHEUMATOID ARTHRITIS. K. D. Salazar, C. B. Copeland and R. W. Luebke. Cardiopulmonary and Immunotoxicology Branch, Environmental Public Health Division, NHEERL, ORD, U.S. EPA, Research Triangle Park, NC. Epidemiological data suggest that occupational exposure to the amphibole-containing vermiculite in Libby, MT was associated with increased risk for developing autoimmune diseases and had an odds ratio of 3.23 for developing rheumatoid arthritis (RA). Our goal was to determine whether exposure to Libby amphibole (LA) modulates the disease course of RA. We utilized the collagen-induced arthritis
(CIA) and the Streptococcal cell wall (SCW) models of RA. The SCW arthritis model induces a local inflammatory reaction in one hind ankle that mimics the physiological milieu associated with RA in humans. The CIA model is a systemic model that produces paw inflammation in all 4 limbs and autoantibodies similar to human patients with RA. To determine if LA affects the onset and progression of RA, female Lewis rats were equally divided into 6 asbestos dose groups and 1 vehicle control group. Rats were intratracheally instilled biweekly for 13-weeks with total doses of 0.15, 0.5, 1.5, 5.0 mg LA or 0.5 or 1.5 mg amosite asbestos (positive control). Following the final instillation, joint inflammation was induced with either the SCW or CIA model. Swelling was quantified with a digital caliper and serum was analyzed for autoantibodies via ELISA and indirect immunofluorescence. Preliminary results from 2 experiments suggest that amosite, but not LA, exposure enhanced the magnitude of ankle swelling in the SCW model. However, neither LA nor amosite exposure affects the kinetics of the join inflammation in the CIA model. Both amosite and LA exposure increased the number of rats with circulating anti-nuclear antibodies (ANA). The majority of ANA-positive animals presented a similar ANA staining pattern which indicates the upregulation of autoantibodies with similar specificity. Future studies will identify the specificity of the upregulated ANA and characterize the effect of amphibole exposure on RA-associated antibodies. This abstract does not reflect EPA policy. 1512 ESR SPIN-TRAPPING INVESTIGATION OF LUNG FREE RADICALS IN AN ANIMAL MODEL OF INTERSTITIAL PNEUMONIA ASSOCIATED WITH AUTOIMMUNE DISEASE. M. B. Kadiiska, H. Miyakawa, J. Jiang and R. Mason. NIEHS/NIH, Research Triangle Park, NC. The lung is frequently involved in autoimmune disease and complications involving the lung include mostly interstitial pneumonia (IP). However, the pathogenesis and mechanisms underlying the development of IP associated with autoimmune disease remain unknown. In this investigation, we studied the free radical generation involved in the development of IP in autoimmune disease murine model by using in vivo spin-trapping methodology. We observed an electron spin resonance (ESR) spectrum of the spin trap α-(4-pyridyl-1-oxide)-N-tert-butylnitrone (POBN) radical adducts detected in the lipid extract of lungs in autoimmuneprone mice after intratracheal instillation of staphylococcal enterotoxin B (SEB). The POBN adducts detected by ESR were assigned as lipid-derived. Their presence was paralleled by infiltration of macrophages and neutrophils in the bronchoalveolar lavage fluid. To further investigate the mechanism of free radical generation, mice were pretreated with the macrophage toxicant gadolinium chloride (GdCl3), which significantly suppressed the free radical generation. Free radical generation was also decreased by pretreatment with the xanthine oxidase inhibitor allopurinol, the iron chelator Desferal, and the inducible nitric oxide synthase (iNOS) inhibitor 1400W. Histopathologically, these drugs significantly reduced both the cell infiltration to alveolar septal walls and the synthesis of pulmonary collagen fibers. Experiments with NADPH oxidase knockout mice showed that NADPH oxidase did not contribute to lipid radical generation. These results suggest that lipid-derived free radical production is essential in the manifestation of IP and that a macrophage toxicant, an XO inhibitor, an iron chelator, and an iNOS inhibitor protect against both radical generation and the manifestation of IP. Therefore macrophage toxicants, XO inhibitors, iron chelators or iNOS inhibitors may be potential therapeutic agents against alveolitis and fibrosis in treating IP. 1513 B1A CELL ACTIVATION BY GLUTAMATE. R. Marcum and J. C. Pfau. Biological Sciences, Idaho State University, Pocatello, ID. Asbestos exposure has been implicated in an increased risk of autoimmunity. Direct exposure to asbestos has not been shown to activate B cells; however asbestos exposure does cause an increase of reactive oxygen species in macrophages. One mechanism by which macrophages may reduce the effects of these reactive oxygen species involves the xCT transporter, which is upregulated on macrophages after asbestos exposure. xCT is an amino acid transporter which imports cystine and exports glutamate. While the role of the imported cystine is likely for synthesis of cysteinebased antioxidants, the function of the exported glutamate in the immune system is not clear. We hypothesize that this exportation of glutamate is involved in the activation of B cells. In this study the presence of glutamate receptors on CH12.LX, a B1a cell line, was investigated by flow cytometry. The glutamate receptors mGluR5 and NMDA receptor were shown to be expressed on the cells. Additional work was done to investigate the effects on CH12.LX cells exposed to asbestos treated macrophage media as well as the effects of glutamate receptor agonist and antagonists. RAW 264.7 macrophages were exposed to asbestos for various time points, and the media was collected. The CH12.LX cells were then treated with media from untreated or asbestos exposed macrophages. Effects from the asbestos treated macrophage media, containing approximately 100μM glutamate, as measured by AmplexRed assay, on CD12.LX cells include a decrease in proliferation and increased production of IL-10. These effects were decreased by treatment with mGluR5 and NMDA receptor antagonists. These results suggest that glutamate is involved in the activation of B1a cells, making the xCT transporter a possible mechanism leading to autoimmune responses following asbestos exposure. 1514 SEX HORMONES DETERMINE WHETHER IL-33 PROTECTS OR EXACERBATES AUTOIMMUNE HEART DISEASE. M. Coronado, D. Bedja, A. Bucek, K. Gabrielson and D. Fairweather. Johns Hopkins University, Baltimore, MD. Autoimmune myocarditis is an inflammatory heart disease that progresses to dilated cardiomyopathy (DCM) and heart failure and occurs at a higher incidence in men than women. In order to determine why disease is worse in men, we inoculated male and female BALB/c mice with 103 PFU of coxsackievirus B3 (CVB3) and cardiac myosin ip to induce autoimmunity. During acute myocarditis (day 10 post infection, pi), males developed more severe myocarditis than females that progressed to DCM by day 35pi. We showed previously that increased CVB3 myocarditis in males is associated with increased numbers of mast cells (MCs) and macrophages that express TLR4 and IL-1b. Interleukin-33 (IL-33) is a Th2 cytokine found to be cardioprotective in a mouse model of cardiac overload, where it reduced hypertrophy and improved survival. ST2 is the receptor for IL-33 that is expressed on MCs, macrophages and cardiac myocytes. Increased levels of soluble ST2 (sST2) in sera correlate with impaired LV function and heart failure. In contrast, administration of recombinant (r)IL-33 in mice increases inflammation in autoimmune models. Here, we found that IL-33 and ST2 levels in the heart were significantly lower in males compared to females at day 10. Gonadectomy (GDX) of males reduced inflammation while increasing IL-33 in the heart. This was reversed with testosterone (TE) replacement in GDX males. GDX males appeared immunologically like females, with reduced TLR4+IL-1b+ macrophages and increased IL-4 and regulatory T cells. Thus, we show that TE reduces cardioprotective IL-33 levels in the heart of males during acute myocarditis. However, when we inoculated male BALB/c mice with rIL-33 we found that males developed significantly increased acute myocarditis and sera sST2 levels compared to PBS controls, similar to results observed in other autoimmune models. We hypothesize that high IL-33 activates TLR4+IL-1b+ MCs and macrophages that express the ST2 receptor resulting in exacerbated disease in males. Thus, sex hormones determine whether IL-33 is protective or damaging to the heart following CVB3 infection. 1515 EFFECT OF TISSUE TRANSGLUTAMINASE ANTIBODIES ON CELIAC DISEASE. R. N. Ndeto and B. Fraij. Biology, Chemistry, Environmental Health Science, Benedict College, Columbia, SC. Sponsor: B. Cummings. Celiac disease comprises intolerance against dietary gluten present in wheat, rye, and barley, and one of to the most common food related life long disorders. Now a day’s celiac disease is conceived as an autoimmune mediated systemic disorder commonly presenting as enterophathy in genetically susceptible individuals. The most obvious features distinguishing celiac disease from other small intestinal enteropathies is the presence of auto antibodies against trans glutamines (TGC or TG2) during gluten containing diet. TGC is known to crosslink gliadin peptides to itself enabling the progression of celiac disease. The celiac disease-specific anti-TGC antibodies can modulate epithelial and neuronal cell as well as vascular biology. We studied if antibodies to tissue transglutaminase (TGC) might increase or decrease the enzymatic activities to TGC and there by enhance its cross linking function. It was reported that the conversion of TGC (80 kDa) to a smaller TG form (55 kDa) increases transglutaminase cross-linking activity. Incubation of lysates from RBC or MDA cells with celiac serum resulted in the conversion of the TGC to TG and increases in cross-linking activity when compared to normal serum, therefore, TGC antibodies might be the causative factor in the development of the extraintestinal symptoms occurring in celiac disease. Normal serum also resulted in the conversion of the TGC to TG and increases in cross-linking activity when compared to control with no serum, a condition that may be comparable to injury or wounds that lead to rapid enzymatic transamidation activation. 1516 THE USE OF DMELS IN REACH RISK CHARACTERIZATION. R. Roy, L. Milchak, N. Pechacek, J. Walton and R. Skoglund. Medical Department, 3M Company, St. Paul, MN. Under the European Union’s Registration, Evaluation, Authorization, and restriction of CHemicals (REACH) regulation, risk characterization (RC) for human health endpoints is done by comparing the ratio (called the Risk Characterization SOT 2011 ANNUAL MEETING 325
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The Toxicologist Supplement to Toxi
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The Toxicologist Supplement to Toxi
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1 BIODEGRADABLE MATERIALS FOR TISSU
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that genetic toxicology data are ge
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well-orchestrated lung inflammation
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scribed in the literature. We have
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years ago). We will illustrate how
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involved in the biodegradation proc
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stem cells but rather a treatment i
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additional compound showed agreemen
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82 COMPARISON OF 3H-THYMIDINE INCOR
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irritants. While in practice these
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alleles are especially vulnerable t
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109 CD4+ T CELL INTRINSIC TNF RECEP
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118 TO STUDY THE SIGNAL TRANSDUCTIO
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PAHs, such as dioxins, are prevalen
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containing substituents and/or hydr
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146 COMPUTATIONAL MODELING FOR QT P
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suggest that the combination of too
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164 TRANSLOCATOR PROTEIN (18 KDA) (
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function as a metal binding protein
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laboratory has demonstrated that NR
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known. The aim of this study was to
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from 5 to 28 days in duration) in e
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positive cells, caspase-3 activatio
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creased level in the 46 kDa preproe
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invasiveness at concentrations repr
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thracene (DMBA,50 μg in acetone, a
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247 CO-CARCINOGENESIS OF N, N- DIET
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sponds to the endosomal dsRNA that
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ODD in both WT (maximum 177% of con
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Lastly, using p53siRNA cells, p53 w
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its receptor Mpl to exert its funct
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294 LOW LEVEL OF LEAD CAN INDUCE PH
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lunar surface presented potential h
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lar about cellular export mechanism
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DNA in the kidney medulla, grandula
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5.00 and 7.50 mg/kg/day by oral gav
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events and carcinogenesis. Here we
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tinization of cells of the hair fol
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358 CHARACTERIZATION OF GENOME-WIDE
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RNAi were also performed to identif
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376 A FUNCTIONAL CROSSTALK BETWEEN
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UGT1A gene induction, while this re
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tivity, specifically peroxisome pro
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and cytotoxic effects; however, its
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histone deacetylase that is necessa
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ment. Paradoxically, buthionine sul
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drug leflunomide and its major (A77
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442 GENE EXPRESSION AND MORPHOLOGIC
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451 INHIBITION OF THE MITOCHONDRIAL
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460 SULFORAPHANE PREVENTS ACETAMINO
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drophilic/lipophilic balance. Other
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pharmacokinetic and toxicological p
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489 USE OF ‘OMICS DATA TO IMPROVE
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498 APPLICATION OF AGE-SPECIFIC ADJ
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507 A DOSE VOLUME TOLERABILITY STUD
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involved the use of an acute inflam
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sorption in the gastrointestinal (G
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(ABC) transporters actively transpo
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545 BEHAVIORAL EFFECTS OF REPIN IN
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a blood pressure phenotype that res
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and inhalation exposure system that
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and lethality associated with these
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position, on vascular reactivity an
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therefore more accurate and reprodu
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commercial chrysotile product that
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elative to their controls. ST-depre
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ats. The majority of the studies fo
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in the China Jintan Child Cohort St
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corneum thickness, cellular epiderm
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645 EVALUATION OF THE IN VITRO EPIS
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654 TCDD ADSORBED ONTO NATURAL AND
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tion revealed no test article-relat
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671 INFLAMMATION AND TISSUE DAMAGE
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model, ethanol was found to inhibit
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689 ENHANCED SUPPRESSIVE FUNCTION O
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NAC + LPS yielded different levels
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707 LIFE-STAGE PBPK MODELS FOR MULT
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downstream of the apical endpoint o
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726 UPDATED ALUMINUM PHARMACOKINETI
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global parameter sensitivity analys
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and renal inflammation induced by 2
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754 PLASMA, URINE, AND TISSUE CONCE
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cently characterized transporter OA
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exposure system was developed from
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lood cell mass and decrease in urin
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practical alternatives to MC in non
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imals dosed with 167 mg/kg THU alon
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and organ weights, clinical signs a
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yet is induced in most bladder and
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830 RISK ASSESSMENT OF THE SPILL: C
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knowledgebase creation. Results are
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852 UNDERSTANDING STRUCTURAL AND PH
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for integrating epidemiology and an
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motor activity, including age of th
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y partial purification of urine (fr
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pacity for self-renewal and may dif
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sue. The depth of our analysis led
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910 IMPLEMENTING CALIFORNIA’S GRE
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concentrations in six tissues and b
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934 THE FDA’S LIVER TOXICITY KNOW
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943 GENOME-WIDE DNA METHYLATION DIF
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membrane localization and subsequen
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trols, respectively. Subtoxic and t
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survival using both smoking regimes
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as non-, weak, moderate, or strong
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988 NNK-INDUCED CYTOKINE ALTERATION
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group (one-way ANOVA, p90 % viabili
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ered as an organ involved in xenobi
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Transport of CPZ across the Caco-2
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estrous cycle and sexual behavior d
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mRNA expression levels. Collectivel
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1043 THE EFFECTS OF ENDOCRINE DISRU
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1052 MONO-2-ETHYLHEXYL PHTHALATE IN
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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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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
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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