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currents have shown that SCBIs have no apparent effect on Na+ channels at hyperpolarized membrane potentials at which channels occupy resting conformations. However, prolonged depolarizations to potentials that promote non-conducting slow-inactivated states increase the affinity for SCBIs, resulting in a slow reduction (“block”) of peak Na+ current amplitude that typically develops over a period of several minutes. These results imply that SCBIs act by selectively stabilizing Na+ channels in slow-inactivated conformations. The state-dependent action of SCBIs is functionally analogous to that of local anesthetic, class I anticonvulsant and class I antiarrhythmic drugs, which preferentially block open and fast-inactivated Na+ channels. These drugs bind to the local anesthetic (LA) receptor, which is formed by residues in the S6 transmembrane segments of at least three of the four Na+ channel homology domains that form the inner ion pore. Several lines of evidence suggest that SCBIs and therapeutic Na+ channel blockers may share a common site of action. In particular, mutagenesis experiments show that residues in Na+ channel DIV-S6 identified previously as elements of the LA receptor, also are important determinants of SCBI binding and action. However, the larger molecular size of SCBIs compared to therapeutic drugs acting at the LA receptor suggests that SCBI binding determinants exist outside the LA receptor and still have yettobedetermined. Supported by NIH grant R01-ES014591. 1354 GABA A RECEPTOR ANTAGONISTS INCREASE FIRING, BURSTING, AND SYNCHRONY OF SPONTANEOUS ACTIVITY IN NEURONAL NETWORKS GROWN ON MICROELECTRODE ARRAYS (MEAS): A STEP TOWARDS CHEMICAL “FINGERPRINTING”. A. M. Johnstone 1 , J. Turner 1 , C. Mack 1 , L. Burgoon 2 and T. J. Shafer 1 . 1 Integrated Systems Toxicology, U.S. EPA, Research Triangle Park, NC and 2 Research Cores Unit, U.S. EPA, Research Triangle Park, NC. Assessment of effects on spontaneous network activity in neurons grown on MEAs is a proposed method to screen chemicals for potential neurotoxicity. In addition, differential effects on network activity (chemical “fingerprints”) could be used to classify chemical modes of action. To test this, we examined effects of 4 GABA A antagonists (bicuculline (BIC), lindane, picrotoxin (PTX), RDX) on network activity in neocortical neurons and compared them to verapamil (VER; Ca 2+ channel antagonist), fluoxetine (FLU; 5HT 3 reuptake inhibitor) and muscimol (MUS; GABA A agonist). Concentration-response relationships for effects on network spike rates were determined using MEAs, followed by analysis of bursting patterns and firing synchrony using Neuroexplorer and custom written software, respectively. GABA A receptor antagonists increased network activity (EC 50 (μM): BIC, 0.41; lindane, 1.9; PTX, 15.2; RDX, 12.3), while the other compounds decreased it (IC 50 (μM): VER 6.9; FLU, 5.4; MUS, 0.4). GABA A receptor antagonists, but not other compounds, also altered #bursts/min, burst duration, and %spikes in bursts. GABA A receptor antagonists increased synchrony of firing (EC 50 (μM): PTX 0.045; RDX, 8; lindane, 0.15). By contrast, MUS (IC 50 = 7.7 nM), VER (IC 50 = 1.0 uM), FLU (IC 50 =1.5 uM) decreased synchrony. While additional chemical classes need to be evaluated, these data confirm that MEAs are useful to screen chemicals for neuroactivity and indicate that analysis of chemical effects on spike rates, burst parameters and synchrony may be useful to develop chemical fingerprints. This approach will improve the predictive nature of MEA data from uncharacterized chemicals by providing mode of action information. This abstract does not reflect Agency policy 1355 EFFECTS OF FIPRONIL ON THE EEG OF LONG- EVANS RATS. D. F. Lyke, K. L. McDaniel, V. C. Moser and D. W. Herr. NB/TAD/NHEERL/ORD, U.S. EPA, Research Triangle Park, NC . We have reported that the non-stimulus driven EEG is differentially altered by deltamethrin or permethrin (Lyke and Herr, Toxicologist, 114(S-1):265, 2010). In the current study, we examined the ability to detect changes in EEG activity produced by fipronil, a phenylpyrazole pesticide that inhibits GABA receptors. Adult male Long-Evans rats were dosed with fipronil (po). Range-finding studies (40 or 50 mg/kg, n=5/dose) were conducted using observations of neurological signs, grip strength, and landing foot splay. The data suggested increased handling reactivity, mild tremors and gait changes, circling, decreased hindlimb grip strength, and increased foot splay. Maximal effects were evident about 5 to 8 hours after dosing. Additional rats were implanted with epidural screw electrodes. After about 1 week recovery, non-restrained animals were gavaged with corn oil and tested for 2 days to 290 SOT 2011 ANNUAL MEETING allow acclimation. On day 3, the rats were dosed with 1 ml/kg vehicle (corn oil), 25 mg/kg fipronil, or 50 mg/kg fipronil and tested 6 h later. EEG was recorded as 30 segments of 2 s durations, transformed using a FFT, and the spectra averaged. Treatment with 25 and 50 mg/kg fipronil decreased the area (17-25% decrease) associated with Gamma activity when recorded between the visual cortex and frontal cortex. The peak amplitude of this Gamma activity was decreased (20% decrease) by 50 mg/kg fipronil. These results differ from the previously reported increases in Gamma activity following treatment with permethrin (11-25% increase in amplitude-area), and lack of changes after dosing with deltamethrin. The data show that fipronil can alter CNS activity as measured by EEG, and the alterations may differ from some other pesticides. This is an abstract of a proposed presentation and does not necessarily reflect EPA policy. 1356 TREATMENT OF CAENORHABDITIS ELEGANS WITH GLYPHOSATE OR MANCOZEB SUGGESTS SELECTIVE NEURONAL DEGENERATION. R. Negga, M. Machen, J. Salva and V. A. Fitsanakis. Biology, King College, Bristol, TN. Previous studies demonstrate a positive correlation between high levels of pesticide usage and Parkinson’s disease (PD), a disease that preferentially targets dopaminergic (DAergic) neurons. In order to better characterize the potential relationship between two common pesticides and specific neurodegeneration, we chronically (24 hours) or acutely (30 min) exposed two different Caenorhabditis elegans (C. elegans) strains to varying concentrations (LC 25 , LC 50 or LC 75 ) of TouchDown (TD: glyphosate) or Manzate (MZ: manganese/zinc ethylene-bis-dithiocarbamate). To further model environmental exposure, additional populations of worms were exposed first to TD for 30 min, followed by a 30-min incubation with varying MZ concentrations. Initially, studies were carried out in NW1229 worms (pan-neuronal::green fluorescent protein [GFP] construct). Pixel counts from fluorescence photomicrographs of worms treated with individual pesticides indicated statistically significant decreases (p < 0.05)in the number of green pixels in the nerve ring (primarily DAergic), ventral nerve cord (primarily GABAergic or chonlinergic) or both regions. This was in contrast to data from the dual treatment, where a statistically significant decrease (p < 0.05) in pixel number was only observed at 20% MZ. In order to further examine the specificity of neurodegeneration following treatment with these agrochemicals, we used EG1285 worms (GABAergic neurons::GFP construct) to verify GABAergic neurodegeneration. Results indicated a statistically significant decrease in number of green pixels associated with GABAergic neurons in both chronic treatment (p < 0.01) paradigms, and in the acute MZ treatment only at 30% (p < 0.001). Visual inspection of photomicrographs suggested that the decrease in pixel number was due to morphological changes in ventral nerve cord GABAergic neurons. Taken together, our data suggest that exposure to TD or MZ promotes neurodegeneration, including that of GABAergic neurons, in the model organism, C. elegans. 1357 EFFECTS OF ATRAZINE AND ITS METABOLITE DIAMINOCHLOROTRIAZINE ON UNDIFFERENTIATED AND DIFFERENTIATING N27 DOPAMINERGIC CELLS. Z. Lin, C. A. Dodd, I. I. Georgieva and N. M. Filipov. Physiology and Pharmacology, University of Georgia, Athens, GA. Multiple in vitro and in vivo studies have shown that excessive exposure to the herbicide atrazine (ATR) results in dopaminergic neurotoxicity, suggesting that ATR targets the dopaminergic circuitry preferentially. However, effects of ATR or of its major mammalian metabolite diaminochlorotriazine (DACT) on dopaminergic cell differentiation are unknown. Hence, we sought to determine the impact of ATR and DACT on undifferentiated and differentiating dopaminergic cells. Immortalized dopaminergic cells (N27) were exposed for 24 or 48 h to a concentration range of ATR or DACT with and without the presence of a differentiating agent (dbcAMP) in the exposure medium. Exposure to 300 μM ATR or DACT caused time-dependent cytotoxicity and decreased ATP production in undifferentiated N27 cells. On the other hand, 48, but not 24 h, exposure to 300 μM ATR or DACT increased the ADP: ATP ratio in both undifferentiated and differentiated N27 cell, indicating that longer exposure to ATR or DACT in these cells may be apoptotic. Morphological examination indicated that exposure to ATR (≥ 60 μM) during differentiation decreased soma size as early as 24 h. In contrast, DACT disrupted N27 cell differentiation by decreasing thin neurite formation at concentrations as low as 12 μM, but only after 48 h incubation. These data demonstrate that
exposure to both ATR and DACT has adverse impact on dopaminergic cells, including a disruption of the normal differentiation process. Moreover, it appears that ATR and DACT affect the dopaminergic cell differentiation process differently. 1358 EFFECT OF HEXACHLOROBENZENE(HCB)ON THE NEURONAL DIFFERENTIATION OF MOUSE EMBRYONIC STEM CELLS. C. Addae and E. Martinez-Ceballos. Environmental Toxicology, Southern University and A&M College, Baton Rouge, LA. Sponsor: R. Uppu. Embryonic stem (ES) cells are pluripotent cells that can differentiate into all three main germ layers: endoderm, mesoderm, and ectoderm. A number of methods have been developed to differentiate ES cells into specific cell types in culture. In preliminary studies, we have found that encapsulation of ES cells in alginate-based hydrogels increases the efficiency of ES cell neuronal differentiation. Now we have made use of this model system to examine the effect that environmental pollutants have on ES differentiation. One of such pollutants, hexachlorobenzene (HCB), is a synthetic industrial chemical that is bioaccumulative, persistent, and a toxic pollutant in the environment. Exposure to this substance is a public health concern because of its association with a wide range of adverse health effects. It is believed that HCB can interfere with brain development and cause mental disorders such as autism. Thus the goal of this research is to investigate the effect of HCB on neuronal differentiation of mouse ES cells. To achieve this goal, ES cells were grown in suspension in ES medium and treated with 10nM HCB for 24, 48, and 72 hours. Fresh medium was added at the end of the treatments and the resulting embryoid bodies (EBs) were harvested on day 8 of culture. Immunofluorescence analysis was performed to examine the effect of HCB on neuronal differentiation. Results showed that HCB has an inhibitory effect on the neuronal differentiation of the mouse ES cells. Because cell death was prominent in HCB-treated ES cells as compared to controls, the dose-dependent effect of HCB on ES neuronal differentiation was also examined. Our studies suggest that low doses of persistent pollutants may affect the differentiating capabilities of ES cells. The relationship of our findings to neurological disorders such as autism is discussed in this work. 1359 INCREASED FREQUENCIES OF MICRONUCLEATED RETICULOCYTES RELATED TO ALDH2 POLYMORPHISMS IN NON-SMOKING AND NON- DRINKING WORKERS EXPOSED TO STYRENE. Z. Weng 1 , D. Guan 2 , X. Zhang 4 , P. Zhao 3 , Y. Zheng 4 and R. Wang 1 . 1 Japan National Institute of Occupational Safety and Health, Kawasaki, Japan, 2 Beijing Fengtai Health Inspection Institute, Beijing, China, 3 Beijing Guoji Zhongyi Hospital, Beijing, China and 4 National Institute of Occupational Health and Poison Control, China, Beijing, China. Sponsor: N. Mei. To determine the effect of occupational exposure to styrene on frequencies of micronucleated reticulocytes (MN-RETs), we recruited 115 reinforced plastic workers and 90 unexposed healthy individuals (both exposure group and control group were non-smoking and non-drinking). In addition, considering genetic polymorphisms can have an effect on styrene-induced toxicity, we evaluated the associations between aldehyde dehydrogenase 2 (ALDH2) polymorphisms and styrene-induced frequencies of MN-RETs. Results showed that frequencies of MN-RETs were significantly increased in styrene-exposed workers than unexposed individuals. In styrene-exposed workers, variant allele ALDH2 *2 was significantly associated with increased frequencies of MN-RETs. However, no effect was observed of ALDH2 polymorphisms on frequencies of MN-RETs in unexposed individuals. Our data indicated that styrene exposure seems to be associated with genotoxicity, and this toxicity may be modulated by ALDH2 polymorphisms. 1360 MODULATION OF DNA REPAIR CAPACITY BY XPC HAPLOTYPES. C. M. Rondelli 1 , J. K. Wickliffe 2 and S. Z. Abdel-Rahman 1 . 1 NCB & ObGyn, University of Texas Medical Branch, Galveston, TX and 2 Environmental Health Sciences, Tulane University, New Orleans, LA. Xeroderma pigmentosum complementation group C protein, encoded by the XPC gene, plays a key role in DNA nucleotide excision repair (NER). XPC is highly polymorphic, with over 90 single nucleotide polymorphisms (SNPs). These SNPs could alter the levels, structure and function of the encoded XPC protein, thus altering DNA repair capacity (DRC). A comprehensive evaluation of all common XPC SNPs on DNA damage-response and DRC has not been performed. We constructed a haplotype map encompassing all XPC SNPs with a minor allele frequency ≥0.05, and identified 21 haplotypes that segregated into 6 phylogenetic groups (PGHs A-F). We evaluated the relationship between these groups of haplotypes and DNA damage associated with smoking, using chromosome aberrations (CA) as a biomarker. We found a significant interaction between one group, PGH- C, and smoking for baseline CA (P=0.046). Using mutagen-sensitivity as an intermediate biomarker of cancer risk, we observed significant interactions between smoking and two groups, PGH-D (P=0.023) and -F (P=0.007). To provide mechanistic explanations to our findings, we exposed human lymphoblastoid cells with different XPC haplotypes to UV radiation, to generate cyclobutane pyrimidine dimers (CPD) and 6-4 photoproducts (6-4PP). Using ELISA, we evaluated the effect of different XPC haplotypes on the repair of CPD and 6-4PP. We hypothesized that if certain XPC haplotypes have functional effects, there would be a correlation between these haplotypes and rate of repair of UV-induced genetic damage. Our preliminary results suggest a preference for the repair of 6-4PP over CPD, and show a significant difference in DRC between different XPC haplotypes. The data provides initial mechanistic explanations of the effects of XPC haplotypes observed earlier in smokers and support the reported associations between XPC SNPs and cancer risk. 1361 DRUG METABOLIZING ENZYME POLYMORPHISMS, RESPONSE TO CHEMOTHERAPY AND SURVIVAL IN LUNG CANCER PATIENTS. A. O. Ada 1 , S. C. Kunak 2 , F. Hancer 1 , S. Bilgen 1 , T. G. Ada 1 , V. Karacaoglan 1 , S. Suzen 1 , S. Alpar 3 , M. Gulhan 3 , B. Kurt 3 and M. Iscan 1 . 1 Toxicology, Ankara University, Faculty of Pharmacy, Ankara, Turkey, 2 Pharmacology, Giresun University, Medical Faculty, Giresun, Turkey and 3 Pulmonary Diseases Clinic, Ataturk Pulmonary Diseases and Thoracic Surgery Hospital, Ankara, Turkey. Lung cancer is an increasing worldwide public health problem particularly in men. In recent years, several polymorphisms in cytochrome P-450s (CYP)s and glutathione S-transferases (GST)s have been reported to be associated with survival rates of patients with non-small cell lung cancer (NSCLC) but the studies in this regard are scarce and the results are contradictory. Moreover, almost no information is available with respect to the relationship between these polymorphisms and response to chemotherapy in NSCLC patients. In this study, CYP1A1, CYP1B1, CYP2E1*5B, GSTM1, GSTO1, GSTP1 exon 5, GSTP1 exon 6 and GSTT1 polymorphisms were determined in 138 NSCLC patients to evaluate their role in survival and response to first-line platinum based chemotherapy. The polymorphisms did not significantly influence the responses to platinum based chemotherapy. Of the studied polymorphisms only GSTP1 exon 6 variant significantly altered (improved) the survival compared to wild type (p=0.036) with median survival of 22.2 months and 16.1 months, respectively. Multivariate analysis also revealed a significant altered (reduced) adjusted hazard ratio of death associated only with the GSTP1 exon 6 variant genotype of 0.45 (95% confidence interval (95% CI), 0.23- 0.89, p=0.022). These results show that a) the studied CYP and GST polymorphisms are not functioning as a predictor of response to first-line platinum based chemotherapy, and b) the GSTP1 exon 6 variant genotype is associated with improved survival in the patients with advanced NSCLC. (Supported by the grants from Research Fund of Ankara University Nos: 2006-08-03-002 HPD, 2007-08- 03-005 HPD, 2008-08-03-006 HPD and 10A3336002) 1362 CYP AND GST GENE POLYMORPHISMS IN A TURKISH POPULATION. M. Iscan 1 , V. Karacaoglan 1 , S. H. Kunak 2 , E. Soydas 1 , T. G. Ada 1 and A. O. Ada 1 . 1 Department of Toxicology, Ankara University, Faculty of Pharmacy, Ankara, Turkey and 2 Department of Pharmacology, Giresun University, Faculty of Medicine, Giresun, Turkey. It is well known that cytochrome P-450 (CYP) enzymes are able to metabolize many xenobiotics including drugs, polycyclic aromatic hydrocarbons and aromatic amines to reactive metabolites which could be very toxic and/or carcinogenic. The glutathione S-transferases (GST)s are a family of cytosolic enzymes generally involved in the inactivation of drugs and toxic, electrophilic, xenobiotics. Thus, genetic polymorphisms of these enzymes can have great impact on the interindividual susceptibility to toxicities of xenobiotics. In this study, CYP2E1, GSTM1, GSTO1, GSTP1 and GSTT1 gene polymorphisms were determined in 302 healthy individuals. On the basis of an improved polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP) methodology, the frequency of CYP2E1*5B (RsaI), GSTO1 (Ala140Asp), GSTP1 codon 105 and GSTP1 codon 114 polymorphisms were determined. The frequencies of c1/c1 (wild type), c1/c2 (heterozygous variant) and c2/c2 (homozygous variant) CYP2E1 genotypes were 94.7 %, 5.3 % and 0 %, respectively. The GSTO1 genotype frequencies were Ala140/Ala140 48.6 SOT 2011 ANNUAL MEETING 291
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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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Page 255 and 256: have now compared the IC50 values b
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gene expression post-transcriptiona
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1595 GENE EXPRESSION PROFILE OF RAT
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to confirm a hepatotoxic property o
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1613 AN INVESTIGATION OF THE CLEARA
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its nuclear translocation was reduc
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were collected from TK animals at d
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egulated targets were selected for
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U/L after tetracycline. Minocycline
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peri-pubertal FasL-/- mice show a d
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showed similar levels of apoptosis
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1676 TWO BIOMARKERS FOR EVALUATION
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motifs selected. This system was ap
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1693 VOC SERUM LEVELS IN THE GENERA
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1702 DOES THE CLOCK MAKE THE POISON
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those with high nickel content are
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isk assessment. However, unique cha
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model of APAP metabolism and glutat
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logically & morphologically similar
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posure, blood chemistry was analyze
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elated to oxidative stress by measu
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ostasis), but work is needed to tra
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tokine products during carcinogenes
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ways as chemical stressors and, the
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toxicity of nanomaterials relates s
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1815 MEASURING COMPOUND SELECTIVITY
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1825 EFFECTS OF METABOLISM BY INTES
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cyanoacetic acid increased 2-3 fold
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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