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ane. Our goal is to determine whether a nitrogen mustard injury heals more slowly than an equivalent UVB injury. To accomplish this, corneal organ cultures were exposed to different levels of UVB to determine conditions that would produce a 24 hr post-UVB phenotype equivalent to the 24 hr post-exposure phenotype of a 60 min exposure to 100 nmol NM. Corneal organ cultures were irradiated 14 cm from the light source for various times to produce different intensities of UVB: 5 min resulted in 100 mJ/cm2, 20 min, 400 mJ/cm2; 40 min, 800 mJ/cm2; 60 min, 1200 mJ/cm2; 80 min, 1600 mJ/cm2; and 100 min resulted in a 2000 mJ/cm2 exposure. To compare these organ cultures to those exposed for 60 min to 100 nmol NM, corneas were embedded in O.C.T. medium, frozen, then sectioned for H&E staining. Micrographs of sections were overlapped to make composites covering the entire diameter of the cornea. From the composites, the length of denuded cornea was calculated as a percentage of the entire width. Our results demonstrated that a 60 min exposure to 100 nmol NM resulted in the epithelium separating from the stroma across 58.3% of the corneal diameter. A nearly equivalent phenotype (producing a 61.7% separation between the cell layers) resulted from the 2000 mJ/cm2 UVB exposure. The time for the recovering epithelium to completely migrate over the stroma was determined, and was shown to take 4 days after NM exposure. In contrast, the equivalent damage from UVB exposure recovered in only 3 days. Supported by RO1 EY009056, U54 AR055073 and P30 ES005022. 2034 SIGNALING MECHANISMS THAT CAN CONTRIBUTE TO THE NEUROPROTECTION AFFORDED BY GALANTAMINE IN GUINEA PIGS EXPOSED TO THE NERVE AGENT SOMAN. G. Kulkarni 1 , M. Akkerman 1 , Y. Aracava 1 , E. X. Albuquerque 2, 1 and E. R. Pereira 1, 2 . 1 Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD and 2 Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore, MD. Treatment of guinea pigs with galantamine, a drug used to treat Alzheimer’s disease, prevents the neurodegeneration induced by organophosphorus nerve agents, including soman [PNAS 103:13220, 2006]. This study was designed to identify mechanisms that may contribute to the effectiveness of galantamine. Male guinea pigs (30-32 days old) were treated with: (i) saline (0.5 ml/kg, im), (ii) galantamine (8 mg/kg, im), (iii) soman (28 μg/kg, sc), (iv) galantamine followed 30 min by soman, or (v) soman followed 15 min by galantamine. All animals, except those challenged with soman alone, survived. Only 50% of the soman-challenged, untreated guinea pigs survived; about 75% of them had mild or no signs of intoxication whereas the remaining 25% presented severe signs of acute toxicity. At various times after each treatment, animals were euthanized, and their brains removed for subsequent protein analysis. At 2 h after treatment with galantamine, levels of heat shock protein 25 (Hsp-25), and ratios of phospho-Akt to total Akt and phospho (ser-136) Bad to total Bad were higher than those measured in brain extracts from saline-injected animals. Both Hsp-25 and phospho (ser-136) Bad are known to promote cell survival. Levels of Hsp-25 were also found to be elevated in brain extracts obtained at 2 h after the soman challenge of guinea pigs that survived with only mild or no signs of acute toxicity. This may represent a compensatory mechanism triggered by the stress induced by soman. Brain levels of Bcl-2 progressively decreased from 2 to 24 h after the soman challenge. Treatment of the guinea pigs with galantamine prevented soman-induced loss of Bcl-2. The results presented herein provide a mechanistic basis for the neuroprotection afforded by galantamine in animals exposed to soman. (Support: NIH Grant UO1NS059344) 2035 GALANTAMINE COUNTERACTS COGNITIVE DEFICITS IN GUINEA PIGS CHALLENGED WITH THE NERVE AGENT SARIN. J. Mamczarz 1 , Y. Aracava 1 , E. R. Pereira 1, 2 and E. X. Albuquerque 2, 1 . 1 Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD and 2 Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore, MD. Epidemiological studies have reported chronic memory decline among victims and first responders of the 1995 Tokyo terrorist attack with the nerve agent sarin (Environ Health Perspect 109:A542, 2001; Environ Health Perspect 109:1169, 2001). This study was designed to test the hypothesis that a single exposure of guinea pigs to a low dose (0.6xLD50) of sarin induces delayed cognitive impairments that are counteracted by treatment with galantamine, a drug that protects 436 SOT 2011 ANNUAL MEETING guinea pigs against the acute toxicity of nerve agents (PNAS 103:13220, 2006). Prepubertal male guinea pigs received: (i) saline (0.5 ml/kg, im), (ii) sarin (25.5 μg/kg, sc), or (iii) sarin followed 1 h later by galantamine (8 mg/kg, im). Three months after the injections, the cognitive performance of the guinea pigs was first tested in the Morris water maze (MWM). Animal received training to a fixed platform position. Training consisted of four consecutive trials a day over 6 consecutive days followed by the probe test on day 7. Compared to saline-injected animals, sarin-challenged guinea pigs showed slower acquisition of the MWM task; only on the 6th day of training did sarin-challenged animals perform as well as control animals. There was also no significant difference in the probe test between sarin- and saline-injected guinea pigs. In the 8-arm radial water maze, the performance of sarin- and saline-injected animals was comparable. Thus, the cognitive impairment developed by sarin-challenged animals is related to the procedural component of learning. Sarin-challenged guinea pigs that were treated with galantamine presented no cognitive impairment in any test. It is, therefore, concluded that: (i) a single exposure to a low dose of sarin triggers the development of cognitive deficits, and (ii) galantamine is an effective antidote to counteract the delayed neurotoxic effects of sarin. (Support: NIH Grant UO1NS059344) 2036 ANALYSIS OF MAP KINASE SIGNALING IN SULFUR MUSTARD TOXICITY USING PHARMACOLOGIC INHIBITORS AND GENE EXPRESSION PROFILING. C. C. Rothwell, C. M. Crum, P. A. Everley and J. F. Dillman. Cell and Molecular Biology, USAMRICD, Aberdeen Proving Ground, MD. Sulfur mustard (SM) is a potent alkylating agent and vesicant. SM exposure activates numerous signaling cascades such as the mitogen-activated protein kinase (MAPK) cascades. These include the ERK, p38, and JNK pathways, which are involved in cell growth, inflammation, and stress signaling. The precise roles of these pathways in SM toxicity have not been elucidated. We used Western blotting along with pharmacological inhibitors and microarray analysis to examine the activation and role of each pathway after SM exposure in primary human keratinocytes. Western blotting revealed increased phosphorylation of p38 and JNK after SM exposure; however phosphorylation of ERK was equivocal, suggesting that growth conditions may impact ERK activation by SM. We used pharmacologic inhibitors to target each MAPK and then compared gene expression profiles to identify SMinduced genes regulated by each MAPK. Cells were pretreated with SB203580 (p38 inhibitor), PD98059 (ERK inhibitor), or SP600125 (JNK inhibitor) before SM exposure. Cells were harvested at 1, 4, and 8h post-exposure, and RNA was extracted for gene expression profiling. Analysis of variance identified genes significantly modulated due to pharmacologic inhibition in SM-exposed cells. Pathway mapping confirmed alterations in SM-induced MAPK signaling due to pharmacologic inhibition. SM-induced expression of IL-6, IL-8, and TNF-alpha inflammatory cytokines was decreased by p38 MAPK inhibition, but not by inhibition of other MAPKs. Based on the number of significant pathways mapped to each MAPK in the presence and absence of inhibitors, the p38 pathway appeared to be the MAPK cascade most responsive to SM. Interestingly, pathway mapping of the microarray data identified potential cross-talk between MAPK pathways and other pathways involved in SM-induced signaling. Mining of these results will increase our understanding of the role of MAPK cascades in SM-induced signaling and may identify additional therapeutic targets for the development of SM medical countermeasures. 2037 THE NEUROPROTECTANT EFFECTS OF DIAZEPAM ALONE AND COMBINATION WITH HISTONES DEACETILASES INHIBITORS IN A RAT MODEL OF STATUS EPILEPTICUS INDUCED BY ORGANOPHOSPHORUS EXPOSURE. F. Rossetti 1 , M. Furtado 1 , M. Addis 1 , B. Robertson 1 , M. Moffet 2 , L. Lumley 2 and D. Yourick 1 . 1 Walter Reed Army Institute of Research, Silver Spring, MD and 2 U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD. The occurrence of status epilepticus (SE) is considered the main cause of brain lesions and morphological alterations that could result in chronic epilepsy. SE caused by nerve agents such as soman (organophosphorus family of chemicals) begins rapidly, continues for hours, and contributes to prolonged physical incapacitation and neuropathology in both rodent and non-human primate species. Identification of neuroprotectants with efficacy against nerve agent-induced brain injury is the subject of the present study. Male Sprague-Dawley (n=69) had SE-induced by LD50 of soman (110 μg/kg, s.c.) and neuropathological effects analyzed 72 hours after.
Diazepam injections and its combination with the histone deacetylase (HDCA) inhibitors, suberoylanilide hydroxamic acid (SAHA) and valproic acid (VPA) were administered and analyzed. Neuropathology was assessed via FluoroJade B staining. The extent of brain damage induced by SE is dependent upon maximum seizure score attained in the period directly after soman exposure; Diazepam treatment, with or without HDAC inhibitors, was not protective of neuronal loss in piriform nuclei; The combination diazepam/SAHA (25 mg/Kg) was more neuroprotective in hippocampus than just diazepam alone; Both SAHA 50 mg/Kg and VPA 25 mg/kg injections increased neuronal loss in thalamus and cortex; Diazepam also prevented some neuronal loss in the Substantia Nigra Pars Reticulata (SNPr). Soman-induced SE caused brain structure-specific injury 72 hours after SE onset. The damage appears in all nuclei of the hippocampus, amygdala, thalamus, piriform and other cortical regions and is not restricted to limbic areas. Soman-induced brain damage is widespread and complex, is differentially affected by combinations of diazepam and HDAC inhibitors, and detailed studies are needed to identify mechanisms and potential. 2038 ACUTE CL2 INHALATION CAUSES NEUTROPHIL RECRUITMENT AND SURFACTANT INACTIVATION IN MICE. C. B. Massa, C. J. Guo, P. Scott and A. J. Gow. Toxicology, Rutgers University, Piscataway, NJ. Chlorine gas has been identified as a potential threat to both civilian and military populations. Acute exposure to high levels of Cl2 gas can cause respiratory dysfunction, which often progresses to severe respiratory distress and death. Much of the available literature describes chronic, low-dose exposure to volatile chlorinated compounds other than authentic Cl2 gas; however the pathology of acute exposure is less well known. We proposed that acute Cl2 exposure leads to direct modification of the components of the lung lining fluid, resulting in surfactant dysfunction and inflammation as initiating events in acute respiratory distress. C57/BL6 mice were exposed to 300 ppm Cl2 for 1 hour. Measures of lung function, surfactant inactivation and inflammation were compared to naive controls at 3, 24 and 48 hrs post injury. Forced oscillation measurements showed increases in lung elastance and altered lung recruitment, with the 24 hr time point being most effected. Contrary to data chronic exposure, there was no evidence of airway constriction. Capillary surfactometry on the Bronchoalveolar lavage (BAL) fluid demonstrated an increase in opening pressure post Cl2, indicating reduced surface-active function. Examination of surfactant protein expression by western blot showed an increase in SP-D with a concomitant loss of SP-B. These changes may mediate the loss of surface activity in the BAL. As well as increased SP-D levels increased cell number within the BAL following exposure indicates the induction of inflammatory processes. BAL cell infiltrate demonstrated a profound neutrophillic component in addition to an increase in macrophage number. BAL protein was not increased, suggesting intact epithelial barrier function. RT-PCR on BAL cells showed increased expression of the Arg1, CCL2, FIZZ1, IL-1b, and PTGS2 genes, with peak change in all genes at 24 hrs. Neither BAL iNOS mRNA or protein were increased, nor were NO3- or NO2-. Whether a common mechanism underlies surfactant inactivation and the inflammatory response is under investigation. NIH HL-086621, ES-005022, ES-007148. 2039 DURATION OF STATUS EPILEPTICUS DOES NOT AFFECT LEVEL OF BRAIN DAMAGE IN SOMAN EXPOSED RATS. K. Bailey 1 ,L.Wierenga 1 ,L.Yang 1 , L. West 1 , C. Wheeling 1 ,M. Furtado 1 ,D. Yourick 1 and L. Lumley 2 . 1 Walter Reed Army Institute of Research, Silver Spring, MD and 2 U.S. Army Medical Research Institute of Chemical Defense, Edgewood, MD. Soman is an organophosphate nerve toxin that inhibits the breakdown of the excitatory neurotransmitter acetylcholine by inhibiting acetylcholinesterase. In rats, exposure to the LD50 (100 μg/kg in 1 ml) of soman can induce status epilepticus (SE), resulting in varying levels of brain damage. Cortical electroencephalographic (EEG) readings and qualitative assessments of regional brain damage can be used to evaluate seizure activity and severity of injury as a result of soman exposure. With the aid of custom MATLAB software that identifies frequency and duration of EEG seizures, comparisons were made between seizure activity and neuropathology measured by computer-aided analysis of silver stained coronal brain sections. We find that there is no significant correlation between duration of EEG seizures during status epilepticus and qualitative measurements of the hippocampus (R2 = 0.19), thalamus (R2 = 0.26), amygdala (R2 = 0.003), piriform cortex (R2 = 0.02), or cortex (R2 = 0.21) in rats euthanized three days after exposure to soman. The lack of significant correlation between the duration of SE and severity of brain damage in rats exposed to soman suggests that antiseizure treatments are not sufficient for minimizing the brain damage suffered from an organophosphate nerve toxin insult. 2040 TWO-HIT MODEL OF CEES SKIN INJURY INVOLVING DNA DAMAGE AND INDUCTION OF INFLAMMATORY MEDIATORS, IN PART VIA OXIDATIVE STRESS, IN SKH-1 HAIRLESS MOUSE SKIN. A. K. Jain 1 , N. Tewari-Singh 1 , M. Gu 1 , S. Inturi 1 , C. W. White 2 and R. Agarwal 1 . 1 Pharmaceutical Sciences, University of Colorado Denver, Aurora, CO and 2 Pediatrics, National Jewish Health, Denver, CO. Sulfur mustard (SM), a bifunctional alkyalating agent, causes severe cutaneous injury characterized by inflammation and delayed blistering. Our recent studies have found that 2-chloroethyl sulfide (CEES), an analog of SM, causes microblisters, inflammation and histopathological alterations similar to SM in SKH-1 hairless male and female mouse skin models. We have also shown that CEES-induced oxidative stress is the major cause of skin inflammatory response, which is via the activation of Akt/MAP kinase and AP1/NF-κB pathways. To further define the mechanisms of CEES-caused skin injury and to establish a link of CEES-induced signaling pathways with its inflammatory responses, here we performed detailed molecular analysis of SKH-1 hairless mouse skin samples exposed to 2 or 4 mg CEES dose topically. Immunoblot analysis showed strong increase in the expression of COX2 (6.5 fold), iNOS (4.1 fold), MMP-9 (5.2 fold) in CEES-treated skin samples compared to controls indicating their involvement in CEES-caused inflammatory responses. A strong phosphorylation of H2A.X at ser139 (3.4 fold) was also observed showing the involvement of DNA damage in CEES-caused skin injury, which could be in part due to CEES-caused oxidative stress reported recently by us in this mouse model. To confirm the role of CEES-caused oxidative stress in the observed DNA damage and induction of inflammatory molecules, mice were given glutathione (GSH) by oral gavage 1 h before CEES exposure. GSH treatment significantly reduced increase in both CEES-caused H2A.X phosphorylation (60%) as well as expression of COX2 (70%), iNOS (52%) and MMP-9 (54%), which possibly led to the observed attenuation in CEES-caused inflammatory responses by GSH reported by us recently. Collectively, our results clearly show a two-hit model of CEES-caused skin injury involving DNA damage and induction of inflammatory mediators, at least in part via oxidative stress, in SKH-1 hairless mouse skin. 2041 EFFICACY OF ENDOTRACHEAL AEROSOLIZATION OF SCOPOLAMINE FOLLOWING MICROINSTILLATION INHALATION EXPOSURE TO SOMAN IN GUINEA PIGS. M. W. Perkins 1 , Z. Pierre 1 , P. Rezk 1 , P. Sabnekar 1 , J. Song 2 , S. Oguntayo 2 , A. Sciuto 1 , B. Doctor 2 and M. P. Nambiar 2 . 1 Analytical Toxicology, U.S. AMRICD, Aberdeen, MD and 2 Closed Head Injury Branch, Walter Reed Army Institute of Research, Silver Spring, MD. Soman (GD) is one of the most toxic chemical warfare nerve agents (CWNA), because it inactivates acetylcholinesterase (AChE) and the complexe ‘ages’ within minutes making it difficult to reactivation by oximes. There are limited studies investigating respiratory toxicity following inhalation exposure to GD, a most predicted route of exposure, if the agent is used in war or terrorism. We are studying respiratory toxicity following endotracheal microinstillation inhalation exposure to GD and evaluating post exposure therapeutics for protection. Here we report the efficacy of post-exposure treatment with aerosolized scopolamine, a muscarinic antagonist that is more effective than atropine against GD exposure. An endotracheal microinstillation inhalation exposure technique was used to aerosolize GD 841 mg/m3 (1.3 LCt50) or saline to anesthetized male guinea pigs and the animals were treated with scopolamine (0.25 mg/kg) 1 min post-exposure. Treatment with scopolamine prevented the reduction in pulse rate and blood O2 saturation and significantly increased the survival in animals exposed to GD. Increased body weight loss returned to controls level in treated animals. Increased bronchoalveolar lavage protein and cell death was returned to normal the AChE and BChE activity remained higher in scopolamine treated animals compared to controls. Post-exposure treatment with nasal scopolamine reduced the changes in various respiratory parameters including bronchoconstriction (Pause) and lung resistance (Penh), at 4 h and persisted 24 h post GD exposure. These results suggests that post-exposure treatment by endotracheal aerosolization of scopolamine protects against lethal dose GD exposure. SOT 2011 ANNUAL MEETING 437
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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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enzoquinone generate ROS and arylat
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teins (e.g. C3, 4, and 5, APOB, VDB
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1293 TRANSFORMING GROWTH FACTOR BET
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mation was decreased to the same le
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1312 EVALUATION OF THE SENSITIVITY
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luted OFR and CRL. Culture media ex
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urinary TCPy levels, blood and brai
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activity. The dose-response curves
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mice, each with 4 dose groups. One
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exposure to both ATR and DACT has a
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third tetratricopeptide repeats (TP
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7d. 28d after TMT injury there was
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subunits. Each cell type was treate
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1394 COMPARATIVE EFFECTS OF METHYLM
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1403 GENOTOXICITY AND PRE-NEOPLASTI
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vated only in high-dose-treated ani
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1421 DOSE-RESPONSE OF NAPHTHALENE-I
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cisplatin; 1.2-, 1.9- and 2.9-fold
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Day 11 and started to recover on Da
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1448 DEVELOPMENT OF A METHOD FOR QU
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1457 GLOBAL GENE PROFILING REVEALS
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cluding mouse and human macrophage,
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model of lung inflammation and host
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1484 NANOTOXICOLOGY AND NANOHEALTH
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throughput in vitro approach was us
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1502 IMMUNOLOGICAL ASPECTS OF AN AN
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(CIA) and the Streptococcal cell wa
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sitizers were 100% concordant among
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1530 MINIMAL RISK LEVELS FOR STYREN
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ical groups in the field of regulat
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vitro with this potentially insect-
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their performance on toxicological
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need for a better understanding of
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1577 AN IN VITRO MODEL SYSTEM FOR A
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gene expression post-transcriptiona
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1595 GENE EXPRESSION PROFILE OF RAT
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to confirm a hepatotoxic property o
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1613 AN INVESTIGATION OF THE CLEARA
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its nuclear translocation was reduc
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were collected from TK animals at d
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egulated targets were selected for
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U/L after tetracycline. Minocycline
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peri-pubertal FasL-/- mice show a d
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showed similar levels of apoptosis
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1676 TWO BIOMARKERS FOR EVALUATION
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motifs selected. This system was ap
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1693 VOC SERUM LEVELS IN THE GENERA
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1702 DOES THE CLOCK MAKE THE POISON
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those with high nickel content are
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isk assessment. However, unique cha
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model of APAP metabolism and glutat
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logically & morphologically similar
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posure, blood chemistry was analyze
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elated to oxidative stress by measu
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ostasis), but work is needed to tra
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tokine products during carcinogenes
Page 389 and 390: ways as chemical stressors and, the
Page 391 and 392: toxicity of nanomaterials relates s
Page 393 and 394: 1815 MEASURING COMPOUND SELECTIVITY
Page 395 and 396: 1825 EFFECTS OF METABOLISM BY INTES
Page 397 and 398: cyanoacetic acid increased 2-3 fold
Page 399 and 400: 1845 IS THE PROMISCUITY OF THE ARYL
Page 401 and 402: crorarray analysis. RT-PCR results
Page 403 and 404: are a family of phase-II biotransfo
Page 405 and 406: ous labs. As a result of positive s
Page 407 and 408: down the doses may produce more tox
Page 409 and 410: spectively. Below 100 mg/l of gemfi
Page 411 and 412: 1900 GENERATION OF PRECISION CUT LI
Page 413 and 414: iomarkers or observation of lesions
Page 415 and 416: creased reticulocytes and lymphocyt
Page 417 and 418: statistically significant interacti
Page 419 and 420: monize sample preparation and analy
Page 421 and 422: NPC and sinonasal cancer in neighbo
Page 423 and 424: showed incidences of lung and nasal
Page 425 and 426: utylbenzenes, exhibited most simila
Page 427 and 428: 1975 DIFFERENTIAL MODULATION OF CYP
Page 429 and 430: organic As to MMA(V) and a lower ca
Page 431 and 432: ole in invasion and metastasis of c
Page 433 and 434: 3T3-L1 cells to low-levels of arsen
Page 435 and 436: 2011 IDENTIFICATION OF A NOVEL VX M
Page 437 and 438: This work was supported by Cooperat
Page 439: 2029 EFFICACY OF ENDOTRACHEAL ADMIN
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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The Toxicologist - Society of Toxicology

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