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egulation. These switches are oxidized by endogenously produced H2O2 and reduced by thioredoxin-2 (Trx2) and mitochondrial GSH systems, and are central components of the mitochondrial redox proteome. These switches are important sites of vulnerability to environmental toxicants, including oxidants, electrophiles and heavy metals. New methods to map the redox dependence of specific mitochondrial proteins include redox-western blotting and mass spectrometry-based redox proteomics. Studies of Trx2 show that the protein is modified by reactive electrophiles and sensitive to oxidation by trace metals, mitochondrial respiratory inhibitors and deficiency in mitochondrial respiratory substrates. Mice overexpressing Trx2 are protected against age-related oxidative stress as indicated by a number of systemic biomarkers. Redox proteomic analyses show that as many as 10% of all mitochondrial protein thiols are partially oxidized or readily oxidized by low rates of H2O2 generation by glucose oxidase. Many of these proteins are more reduced in Trx2 transgenic mice, which also have lower mitochondrial H2O2 production than wt littermates, suggesting that a fraction of mitochondrial protein thiols is dynamically regulated. The emerging data from studies of the mitochondrial proteome show that environmental exposures, age, diet and availability of metabolic fuels, interact to determine the oxidation of Trx2. Kinetic limitation of electron flow from Trx2 to peroxiredoxin-3 indicates that these factors changing Trx2 redox state affect a diverse subset of mitochondrial proteins which includes key sites of susceptibility to chronic toxicity. 1424 IRON, LYSOSOMAL FRAGILITY, AND MITOCHONDRIAL DYSFUNCTION. J. J. Lemasters. Center for Cell Death, Injury and Regeneration, Departments of Pharmaceutical & Biomedical Sciences and Biochemistry & Molecular Biology, Medical University of South Carolina, Charleston, SC. Iron exacerbates many toxicities and disease processes in liver and other organs and is a catalyst for hydroxyl radical formation from superoxide and hydrogen peroxide. Lysosomes are a cellular repository of chelatable iron. Various injuries and stresses lead to lysosomal breakdown and release of chelatable iron, which is taken up into mitochondria by the mitochondrial calcium uniporter to promote intramitochondrial generation of hydroxyl radicals and other reactive oxygen species (ROS). ROS formation promotes onset of the mitochondrial permeability transition and both apoptotic and necrotic cell death. Desferal, an iron chelator, and inhibitors of the calcium uniporter prevent mitochondrial iron uptake, ROS formation and consequent cell death in oxidative stress and hypoxia/ischemia. This pathway of intracellular iron translocation is a potential therapeutic target against oxidative stress–mediated toxicity. The common occurrence of iron imbalance in aging and the complex interactions of toxic metals, oxidative stress and mitochondria-mediated toxicity make this a critical subject for future human toxicology research. 1425 MITOCHONDRIAL OXIDATIVE STRESS: IMPLICATIONS FOR CELL DEATH. S. Orrenius, E. Norberg, V. Gogvadze and B. Zhivotovsky. Institute of Environmental Medicine, Division of Toxicology, Karolinska Institutet, Stockholm, Sweden. In addition to the long established role of the mitochondria in energy metabolism, regulation of cell death has emerged as a second major function of these organelles. This, in turn, seems to be intimately linked to their role as the major intracellular source of reactive oxygen species (ROS), which are mainly generated at Complex I and III of the respiratory chain. Excessive ROS production can lead to the oxidation of macromolecules and has been implicated in mtDNA mutations, ageing, and cell death. Although mitochondrial dysfunction per se can result in ATP depletion and necrosis, these organelles are also involved in the regulation of apoptotic cell death by mechanisms that have been conserved through evolution. Hence, many toxic agents target the mitochondria and cause the release into the cytosol of cytochrome c and other pro-apoptotic proteins, which can trigger caspase activation and other key events in apoptosis. Cytochrome c release occurs by a two-step process that is initiated by the dissociation of the hemoprotein from its binding to cardiolipin in the inner mitochondrial membrane (IMM). Similarly, Apoptosis Inducing Factor (AIF) must also be detached from the IMM, before it can be exported from the mitochondria into the nucleus. This occurs by proteolytic cleavage of the peptide chain that anchors it to the IMM. AIF cleavage is catalyzed by mitochondrial calpain and preceded by carbonylation of AIF triggered by mitochondrial ROS production. Subsequent release of cytochrome c and AIF into the cytosol occurs via pores in the outer mitochondrial membrane formed by pro-apoptotic Bcl- 2 family proteins, or by Ca2+/ROS-induced mitochondrial permeability transition, although the latter mechanism might be more closely associated with necrotic cell death. Hence, it is apparent that mitochondrial ROS generation is critically involved in the control of both apoptotic and necrotic cell death and an important mediator of mitochondrial toxicity. 1426 METHODS TO DETECT MITOCHONDRIAL TOXICITY CAUSED BY ANTI-RETROVIRAL AND ANTIBACTERIAL THERAPY. S. Nadanaciva. Pfizer R&D, Groton, CT. Sponsor: B. Zhivotovsky. Nucleoside reverse transcriptase inhibitors (NRTIs) given in the treatment of HIV infection cause mitochondrial toxicity since DNA polymerase gamma, the enzyme responsible for replicating mtDNA, is highly sensitive to certain NRTIs. Many of these drugs have received Black Box warnings by the Food and Drug Administration. Another class of drugs, antibacterials which are bacterial protein synthesis inhibitors, can also cause mitochondrial toxicity since there is a structural similarity between bacterial ribosomes and the host’s mitochondrial ribosomes. Both classes of compounds have the overall effect of reducing the level of proteins encoded by mtDNA. In order to reduce compound attrition caused by these compounds, methods to detect changes in mtDNA-encoded protein levels have been developed. This talk will focus on two of these methods. One of these is a high content imaging assay and the other is a lateral-flow immunoassay. The levels of a mtDNA-encoded protein made on mitochondrial ribosomes and a nuclear DNAencoded protein level made on cytosolic ribosomes are measured in both assays. The results from these assays show that (1) the anti-retrovirals impair mtDNA-encoded protein levels with rank order of potency: 2’-3’-dideoxycytidine > 2’-3’- dideoxyinosine > Stavudine > Lamivudine, Abacavir; (2) some of the antibacterials which inhibit either bacterial protein synthesis (e.g. the oxazolidinones) or bacterial DNA synthesis (e.g. the fluoroquinolones) impair mtDNA-encoded protein levels; in contrast, antibacterials which inhibit bacterial cell wall synthesis or disrupt the bacterial lipid membrane do not reduce mtDNA-encoded protein levels. The utility of (a) the high content imaging assay as part of a suite of screens positioned early in the drug discovery process for identifying mitochondrial toxicity and (b) the lateral-flow immunoassay for analyzing clinical samples of patients on anti-retroviral therapy will be discussed. 1427 THE FETAL BASIS OF ADULT DISEASE. D. A. Delker 2 and E. J. Tokar 1 . 1 NCI at NIEHS, Research Triangle Park, NC and 2 University of Utah School of Medicine, Salt Lake City, UT. Recent studies provide convincing evidence for the fetal basis of adult disease. Gestation is a period of high sensitivity to toxicants, with a variety of maternal exposures leading to consequent diseases such as cancer, atherosclerosis, hypertension, obesity, and diabetes in the offspring often much later in adulthood. There is strong suspicion that embryonic/fetal stem cells (SCs) are key targets in the transplacental chemical attack that is the etiological basis of these diseases, in part because of their relative abundance and their role in organogenesis and differentiation. The long latency period between in utero exposure and development of adulthood diseases is consistent with lesions in conditionally immortal SC populations with their limitless capacity for self-renewal. Beginning with the theory of the fetal basis of adult disease (the Barker Hypothesis) and how it relates to alterations in SCs and SC numbers, the symposium will then describe the impact of transplacental arsenic exposure on skin SC dynamics, illustrating how early life arsenic exposure plays a role in skin cancer much later in life. The transplacental arsenic-induced changes in liver programming associated with accelerated atherosclerosis in adulthood, and the effects of maternal lead (Pb) exposure on the hypothalamic-pituitary-adrenal axis and development of Pb-associated adult diseases will then be covered. Next, in vitro SC model systems demonstrating arsenic transforms SCs into a pluripotent cancer SC (CSC) phenotype and how this phenomenon may be specific to arsenic as opposed to other carcinogenic metals (e.g. cadmium) are described. Concluding this session, our panel of experts will discuss genomic profiling of SC signaling pathways in adult animals following environmental chemical exposure and how the activation of these pathways in vivo may predict tumor outcome. This session will be of interest to those researching developmental exposure to metals and other toxicants, metal toxicology, molecular mechanisms involved the regulation of SCs, and the initiation of CSCs, as well as those interested in the fetal basis of adult disease. 1428 MODULATION OF HUMAN STEM CELLS DURING IN UTERO EXPOSURES TO TOXICANTS: A MECHANISTIC EXPLANATION TO THE BARKER HYPOTHESIS. J. E. Trosko. Department Pediatrics/Human Development, Michigan State University, East Lansing, MI. In principal, chemicals might affect cells by mutagensis, cell killing or alteration of gene expression (epigenetic toxicity). It is assumed that chemical toxins/ toxicants are not mutagenic to genomic DNA of the stem cells; however at non-cytotoxic lev- 302 SOT 2010 ANNUAL MEETING
els, they disrupt homeostatic control of proliferation, differentiation, senescence and apoptosis by triggering oxidative stress-induced intra-cellular signaling in adult stem cells, progenitor and differentiated cells, in and between tissues, to modulate gene expression and gap junctional intercellular communication (GJIC). Because adult stem cells and GJIC exist in all organs, disruption of the quality and quantity of stem cells and gene expression, especially during embryogenesis and fetal development, can lead to both (a) immediate birth defects and ( b) chronic diseases, such as cancer, atherosclerosis, diabetes, immunotoxicity, reproductive- and neurological- disorders later in life. The Barker hypothesis might be explained by pre-natal exposures that lead to altered stem cell numbers, thereby increasing or decreasing the risk to diseases, dependent on stem cells, later in life. Non-mutagenic chemicals, which can induce differentiation and GJIC of stem cells, can be either beneficial or detrimental. 1429 FETAL ARSENIC EXPOSURE ENHANCES SKIN CANCER IN ADULTHOOD WITH CONTEMPORANEOUS DISTORTION OF TUMOR STEM CELL DYNAMICS. M. P. Waalkes. NCI at NIEHS, Research Triangle Park, NC. Arsenic is a carcinogen with transplacental activity that appears to impact human skin stem cell population dynamics in vitro. Keratinocyte stem cells (KSCs) are thought to be an important target in skin carcinogenesis. Thus, we tested the effects of in utero arsenic exposure on skin cancer in Tg.AC transgenic mice, a strain sensitive to skin carcinogenesis via activation of the v-Ha-ras transgene likely in KSCs. After in utero arsenic exposure, offspring received topical 12-O-tetradecanoyl phorbol-13-acetate (TPA) through adulthood. Arsenic alone had no effect, while TPA alone induced papillomas and squamous cell carcinomas (SCC). With in utero arsenic exposure before TPA mice developed well over twice as many SCC than with TPA only. Tumor levels of v-Ha-ras transcript were three times higher with arsenic plus TPA than with TPA alone, and v-Ha-ras was over expressed as an early event in arsenic treated fetal skin. Tumor transcript levels of CD34, a KSC marker, and Rac1, a key gene in KSC self renewal, were greatly increased with arsenic plus TPA versus TPA alone, and were similarly elevated in arsenic treated fetal skin. Over expression of Rac1 protein and greatly increased CD34 positive putative KSCs were observed in tumors induced by arsenic plus TPA. Thus, in utero arsenic exposure, though alone oncogenically inactive, stimulates skin cancer in association with distorted skin stem cell signaling and population dynamics, implicating stem cells in the fetal basis of cancer in adulthood. 1430 TRANSPLACENTAL ARSENIC EXPOSURE INDUCED CHANGES IN LIVER PROGRAMMING ASSOCIATED WITH ACCELERATED ATHEROSCLEROSIS. J. C. States 1 , A. Singh 2 ,T. Knudsen 2 , E. Rouchka 3 ,M.S.Ko 5 , Y. Piao 5 ,N.O. Ngalame 1 , J. Arteel 1 , G. Arteel 1 and S. Srivastava 4 . 1 Pharmacology & Toxicology, University of Louisville, Louisville, KY, 2 Molecular, Cellular & Craniofacial Biology, University of Louisville, Louisville, KY, 3 Computer Engineering & Computer Science, University of Louisville, Louisville, KY, 4 Medicine, University of Louisville, Louisville, KY and 5 Laboratory of Genetics, National Institute on Aging, Baltimore, MD. In utero exposure to toxicants can predispose to development of chronic adult diseases. Cardiovascular disease is elevated in areas of endemic exposure to arsenic in drinking water. The role that in utero arsenic exposure plays in development of atherosclerosis underlying the cardiovascular disease is unknown. We showed that in utero arsenic exposure accelerates atherosclerosis in the ApoE-knockout mouse. Liver dysfunction plays a central role in development of the inter-related chronic diseases metabolic syndrome, diabetes and atherosclerosis. Using a genomics approach, we investigated effects of in utero arsenic exposure on liver developmental programming. Pregnant dams were provided drinking water with or without 85 mg/L NaAsO2 from gestational day 8 – 20. Abundances of both mRNAs and miRNAs were evaluated by microarray analyses of total RNA from livers of exposed and unexposed progeny on the day of birth (PND1) and at age 10 weeks (PND70). Plasma biomarkers of liver injury were elevated in 10 week old mice exposed to arsenic in utero. These results along with analyses of the microarray data are consistent with epigenetic changes altering liver development and hepatic inflammatory responses that may contribute to the acceleration of atherogenesis caused by prenatal arsenic exposure in ApoE-knockout mice. Supported by PHS grants R21ES015812, R01ES011314 & P30ES014443, UofL Center for Genetics and Molecular Medicine pilot grant, UofL Collaborative Planning and Development Grant and Intramural Research Program of NIA/NIH 1431 PERMANENT EFFECTS OF MATERNAL LEAD (PB) EXPOSURE ON THE HPA AXIS: A BIOLOGICAL UNIFYING MECHANISM FOR PB-ASSOCIATED ADULT DISEASES. D. A. Cory-Slechta. Department of Environmental Medicine, University of Rochester School of Medicine, Rochester, NY. A major hypothesis underlying early life permanent physiological programming involves fetal exposure to excess glucocorticoids, leading to increased risk of cardiovascular (hypertension), metabolic (obesity), neuroendocrine (type 2 diabetes) and various behavioral and psychiatric disorders (schizophrenia, attention deficit disorder). Our studies demonstrate that maternal only Pb exposure may produce similar permanent physiological changes through effects on the hypothalamic-pituitary-adrenal (HPA) axis. Specifically, developmental only exposures to low levels of Pb in rats initiated 2 mos prior to breeding of dams and continuing until offspring were weaned and associated with blood Pb values of approximately 10-35 ug/dl, produce permanent HPA axis dysfunction in offspring of both genders. These changes were reflected in dynamic alterations in corticosterone levels throughout adulthood, altered behavioral and corticosterone responses to stress challenges, and reductions in the ability of dexamethasone to suppress corticosterone. The latter suggest alterations in delayed glucocorticoid negative feedback, and resulted in a hypercortisolism which was more prominent at the lower than higher blood Pb levels. Collectively, these findings may provide a plausible biological unifying mechanism for the diverse diseases and disorders that have now been associated with environmental Pb exposure, including obesity, hypertension, diabetes, anxiety, schizophrenia and depression, all of which have been related to HPA axis dysfunction. In addition, elevated glucocorticoids lead to hippocampal neuronal death and have been postulated to play a role in Alzheimer’s disease, which has also recently been linked to environmental Pb exposure. Studies are needed to define the lowest Pb exposure levels associated with such effects and their possible epigenetic basis. Moreover, because these effects are induced by maternal Pb exposure, they underscore the need for blood Pb testing in pregnant women at risk of elevated Pb exposure. 1432 ARSENIC-INDUCED STEM CELL INITIATION PRODUCES A CANCER STEM CELL PHENOTYPE DURING MALIGNANT TRANSFORMATION. E. J. Tokar. NCI at NIEHS, Research Triangle Park, NC. Emerging evidence indicates that cancer stem cells are the true malignant cells within tumors and are carcinogenically initiated from normal stem cells or their close, partially differentiated progeny. Recent reports show that arsenic has transplacental carcinogenic activity in mice and probably humans. In mice, fetal arsenic exposure causes tumors and oncogenic lesions throughout the urogenital system much later in life. This greatly delayed response suggests that arsenic targets a stem cell population, possibly producing quiescent cancer stem cells that then induce cancer upon stimulation much later in life. This presentation will first discuss arsenic-induced transformation of human and rodent stem/progenitor cells, followed by a description of primary events and genetic alterations involved in this initiation of cancer stem cells. These alterations include an early loss of stem cell selfrenewal gene expression (p63, ABCG2, BMI-1, SHH, OCT-4, NOTCH-1) that is subsequently reversed as the tumor suppressor gene PTEN is progressively suppressed and cancer stem cell phenotype acquired. This phenotype appears to be associated with aberrant expression of at least some imprinted genes. This indicates that arsenic, a ubiquitous environmental contaminant and known human carcinogen, can directly transform stem/progenitor cells into a pluripotent cancer stem cell phenotype. A comparison of acquired cancer stem cell characteristics in isogenic arsenic-, cadmium, and N-methyl-N-nitrosourea-transformed cell lines indicates that arsenic is much more prone to modifying stem cell populations and precipitating cancer stem cell formation. Thus, arsenic-induced carcinogenic initiation appears to be at the stem cell level. 1433 EPIGENETIC SIGNALING AS A TARGET FOR CHEMICAL TOXICITY AND CARCINOGENESIS. D. A. Delker 1 and W. O. Ward 2 . 1 University of Utah School of Medicine, Salt Lake City, UT and 2 U.S. Environmental Protection Agency, Research Triangle Park, NC. Epigenetic regulation of cell differentiation and organ development is a natural process targeted in disease and chemical toxicity. Stem cells and their progenitors are essential for the development and maintenance of normal tissue function. These cells are characterized by specific gene methylation patterns and RNA profiles including microRNAs and alternative RNA splicing not observed in differentiated cells. Recent studies suggest that the disruption of epigenetic signaling occurs very early in the cancer process and that epigenetic abnormalities are more widespread SOT 2010 ANNUAL MEETING 303
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The Toxicologist Supplement to Toxi
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The Toxicologist Supplement to Toxi
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1 BIOLOGICAL PATHWAY ANALYSIS: AN I
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11 ICH INITIATIVES FOR CONDUCTING P
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models. Experimental approaches and
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30 SILICA AND ASBESTOS IMMUNOTOXICI
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40 NONCANCER TOXICITY POTENTIAL AT
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ased products for patient administr
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nase regulates Hsp27-induced reorga
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exposure resulted in splenomegaly.
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We investigated the effect of imati
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well plate prevented free cell move
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98 DERIVING SIGNATURES OF IN VIVO T
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sulfate, cinnamic aldehyde, 2,4-din
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The final product will be a system
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mercially available STP brands by m
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for six weeks, with 10 mg/kg azoxym
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eceived RES post-TCDD exposure when
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morigenesis. Knocking down of JARID
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163 MICROPET IMAGING OF [18F]-DFNSH
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These results are comparable to tha
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activity as assessed by lever press
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for measured physico-chemical param
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199 DEVELOPMENT OF A MULTIPARAMETER
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To cause PLD, a drug needs to enter
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In contrast to the parent PBDEs and
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transiently transfected HEK 293 cel
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TCDD exposure, 24 h prior to a 20 %
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244 NON-ADDITIVE EFFECTS OF PCB153
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253 COMPARISON OF MIXTURE TOXICITY
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two cerium oxide nanoparticles of v
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271 SIZE-DEPENDENT EFFECTS OF TUNGS
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adigms such as Tox 21 and Toxcast,
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QDs with emission maximum at 800nm
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Cleveland, while others were found
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without the need of animal testing.
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Conclusions: These results are cons
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ing oxime reactivation and organoph
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335 A NON-OXIME IMPROVES SURVIVAL I
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alties suffer from permanent lung i
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ies have established inflammatory b
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363 GENETIC VARIATION IN ISOGENIC M
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372 EVALUATING THE BIOLOGICAL INTER
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dose of 1/20 LD50 (400 mg/kg.bwt) f
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median CR-adjusted isoflavone conce
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data indicate that AhR deletion pro
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February 2006). The rabbit is one o
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tal neurotoxicity (DNT) test (OECD
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of selected microorganisms that are
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BVI. Histopathological analysis was
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446 MOLECULAR CLONING AND CHARACTER
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portant in predicting risk. CYPs 1A
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ats, which involves metabolic activ
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473 BOVINE CORNEAL OPACITY AND PERM
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482 TYPE III DEIODINASE (D3) IS PRO
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tancy evaluation and ranking of bat
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501 CHARACTERIZATION OF ESTERASE, G
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510 REDOX CYCLING BY ENDOGENOUS 2-
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prostate cancer cells. All 8 BEL de
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metallic nickel nanoparticles. Acti
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variety of more or less reactive ch
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550 QUALIFICATION STRATEGIES-GENOTO
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ferentiation, and 3) how mixtures o
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572 LOW-CHRONIC ARSENIC EXPOSURE: E
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582 IDENTIFICATION OF SENSITIVE URI
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duced by the genetic outcross of fe
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fects of new compounds are equally
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acterize the current state of the s
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620 CHARACTERIZATION OF POTENTIAL I
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ways. Moreover, both MAP kinase and
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641 POPS IN THE U.S. POPULATION AND
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studies such as the NCS, consider h
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the beginning of the academic caree
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trophil infiltration, a significant
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tactic response and optokinetic res
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usually high spontaneous PIG-A MFs.
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699 PROMUTAGEN ACTIVATION AND P450
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oxodG in bone marrow, spleen, kidne
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718 GENOTOXICITY OF ORGANIC EXTRACT
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ment were 18.0 and 4.5 nM for BEAS-
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strongest activation of nuclear fac
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746 MACROPHAGE INHIBITORY CYTOKINE-
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screening of cell migration. High-c
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dase inhibition). In contrast, inhi
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mice; the decrease was more pronoun
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Markers of oxidative damage reached
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793 PULMONARY RESPONSE, OXIDATIVE S
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cilitate clinical and industrial ap
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sion of p-p38, p-p53, p21 and cycli
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821 KIDNEY INJURY MOLECULE-2 GENE D
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commercial applications, and have b
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developmental effects. The residual
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strand breaks in an in vitro model
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etate (immunotoxicity). 2,4-D was t
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867 MELATONIN AMELIORATES CYCLOPHOS
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pharmacokinetic (PBPK) models. Ten
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of radiolabeled Mn (carrier-free 54
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893 UNVEILING ASSOCIATIONS BETWEEN
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using area under the concentration
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912 COMMERCIAL FISH DIETS INDUCE VI
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922 A STUDY OF PHOTOTOXICITY FOLLOW
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from 0.1 to 2.9 g/L (saturated vapo
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vasive method for assessing several
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950 ARSENITE DOWN-REGULATES THE CAR
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inflammatory signaling is altered b
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treated wood. Seventy-five of 132 w
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ergy homeostasis and raising levels
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treated with mercury and then with
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997 IN VIVO CORRELATES OF THE MANGA
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of the panel. The panel was compris
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sponse, location, and severity scor
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tant source of n-3 fatty acids such
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old for serious, irreversible or es
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1045 SUBCHRONIC TOXICITY EVALUATION
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sites collected 3 days after inject
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1063 MOLECULAR MECHANISM OF OLANZAP
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esponses, and can be available for
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hence more physiologically relevant
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thesized apoproteins, so we tested
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vate CYP3A5 but could be released b
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1108 STYRENE-INDUCED TOXIC EFFECTS
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1118 THE PRESENCE OF DIETHYL FUMARA
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zebrafish cells were first exposed
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utene-1,4-dial, which has been show
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groups, largely due to lower non-HD
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Exposure to gluten in individuals w
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contrast to VGSC activators such as
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Page 263 and 264: permeability (calcein), mitochondri
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Page 313 and 314: the level in urine was 25% of the m
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Page 329 and 330: numbers of IFN-γ producing cells w
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Page 349 and 350: Expression of the β6 integrin (Itg
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oxetine (30 mg/kg reduced to 15 mg/
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eleased from necrotic cells where i
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plants, they are present in surface
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ferentiation (quantitative in-cell
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control for macrophage activation).
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to 0.5μg/ml. Minimal inhibitory co
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lines tested. Given that dex and AT
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tion in the absence of an immune re
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treated rats had lower calcium load
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1740 PROFILING COMPOUNDS WITH CARDI
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dothelial cells confirmed caveolin-
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1758 GINKGO BILOBA EXTRACT INDUCES
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arin-induced suppression of MDR1 ex
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1780 ANTIANDROGENIC AND ANTIPROLIFE
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included in the evaluation, most of
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1799 GUIDANCE ON THE APPLICATION OF
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However, substances with EC3 values
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1816 CD-INDUCED EGFR TRANSACTIVATIO
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1826 KERATIN 7 EXPRESSION IN INDEPE
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centa were collected at the time of
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1845 SYSTEMATIC SCREENING OF YEAST
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underlying the development of co-mo
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eing measured in experimental roden
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ufactured in the US for more than 3
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nine (N7-THB-Gua) and N7-hydroxyphe
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1892 EFFECT OF LAMBDA-CYHALOTHRIN O
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22 in Phase I. Antimicrobial pestic
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kinetic and dynamic differences, an
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iphenyl, saccharin and melamine was
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1930 DEVELOPMENT OF A RELATIVE SOUR
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1939 MODE OF ACTION FOR THE CANCER
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human was about 1.5-fold lower (60
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Disruption of BDEC integrity in alp
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1968 A HUMAN HEPG2 LUCIFERASE ASSAY
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in the offspring during tumor devel
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een developed to investigate perfus
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to 131.73 μg/mL for KLH-specific I
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cell lines (ATCC) were cultured in
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flammation and xenobiotic metabolis
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vide many contributions: with its g
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to-metal joint replacement. For exa
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to be addressed or negotiated. Deci
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especially with anti-TNF therapies.
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genic line Tg(are:eGFP) was created
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2074 COMPUTATIONAL ASSESSMENT OF TH
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2084 INHIBITION OF 11β-HSD1 DECREA
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(T) and express several enzymes inv
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2101 GENISTEIN MODULATION OF BLOOD
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males per group were dosed orally o
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ate the feasibility of assessing re
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changed. Hepatic protein carbonyl l
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sought to examine alterations in he
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2147 A SINGLE AMINO ACID CONTROLS T
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Gstm7) was independent of both CAR
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ility of tungsten trioxide (WO3), t
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ured by real-time PCR array and rel
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glucose, and creatinine levels, and
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Several studies have reported suppr
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exposure between TCDD-exposed labor
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Furthermore, with increasing number
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Society of Toxicology 2010 Author I
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Society of Toxicology 2010 Abstract
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49 th Annual Meeting and ToxExpo A
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The Official Journal of the Society
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The Toxicologist - Society of Toxicology

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