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(RPTC) cell death, indicating that calpain 10 is required for viability. The goal of these experiments was to ascertain if mitochondrial calpain 10 levels decrease following toxicant exposure and determine the mechanism of mitochondrial calpain 10 degradation. Primary cultures of RPTC were treated with 0.4 mM tert-butylhydroperoxide (TBHP), 0.1 mM cisplatin, 5 μM A23187 or diluent. In addition, isolated mitochondria or matrix were pretreated with 10 μM MG132, 10 μM epoxomicin, 10 μM calpeptin, 10 μM CYGAbuK (calpain 10 inhibitor), Protease inhibitor cocktail (1:100 according to manufacturer’s instructions) or diluent and incubated for various times. Calpain 10 was measured by immunoblot analysis in mitochondria, matrix and cytosolic fractions. RPTC treated with the oxidant TBHP, resulted in a 52% decrease in mitochondrial calpain 10 protein levels at 45 min and remained decreased at 24 hr. In cisplatin-treated RPTC, mitochondrial calpain 10 levels decreased 35% only at 24 hr. A23187-treated cells showed no change in mitochondrial calpain 10 levels. In isolated mitochondria, calpain 10 protein levels decreased 60% and 70% at 30 and 120 min, respectively. Using various protease inhibitors, only MG132 blocked calpain 10 degradation in mitochondria and matrix. These results demonstrate that oxidant injury in RPTC causes a rapid degradation and prolonged reduction in mitochondrial calpain 10 levels. In contrast, cisplatin and A23187 did not elicit a robust oxidant injury and mitochondrial calpain 10 levels did not decrease extensively. The protease inhibitors provide evidence that calpain 10 is degraded in the matrix by Lon protease. The loss of mitochondrial calpain 10 following oxidant injury is consistent with reports that Lon protease degrades oxidized proteins in the matrix. Supported by NIH ES012239. 750 MITOCHONDRIAL HOMEOSTASIS AFTER ACUTE KIDNEY INJURY: SUSTAINED ALTERATIONS IN MITOCHONDRIAL PROTEINS, FUSION/FISSION, AND BIOGENESIS. J. A. Funk, B. E. Shaner and R. G. Schnellmann. Pharmaceutical and Biomedical Sciences, Medical University of South Carolina, Charleston, SC. Mitochondrial dysfunction is a pathological process that occurs after acute kidney injury (AKI), and at this time the state of mitochondrial homeostasis during the initiation and recovery phases of AKI remains unclear. Thus, we examined changes in mitochondrial respiratory proteins, fusion/fission processes, and biogenesis in a non-lethal, rat model of myoglobinuric AKI. AKI was induced by glycerol injection into the hind limbs of male SD rats. Rats had reduced kidney function as determined by a rise in SCr levels from 0.5 to 2 mg/dL 24h after injection. Recovery of kidney function initiated between 24 and 72h with SCr levels decreasing to 1.3 mg/dL at 72h, and continued to decrease to control levels at 144h. Cleaved caspase-3 was observed in glycerol-treated rats between 24 and 144h post-injury. Respiratory proteins NDUFB8, ATP synthase β (ATPβ), and cytochrome c oxidase subunit I (COXI) were decreased from 24 to 144h after injection, suggesting loss of mitochondria and function. Mitochondrial-encoded genes ND6 and COXI mRNA were decreased at 72h and 144h, whereas mRNA levels for the nuclear-encoded genes NDUFB8 and ATPβ either did not change (NDUFB8) or were elevated throughout the study (ATPβ). Expression of mitochondrial fission/fusion proteins, dynamin-related protein (Drp1) and mitofusin 2 (Mfn2), were elevated at 24h and throughout the course of the study. We observed increases in markers of mitochondrial biogenesis, including elevations in PGC-1α, PGC-1 related coactivator (PRC), and nuclear respiratory factor (NRF)-1 mRNA levels and elevations in PGC-1α, NRF-1, and (Tfam) protein levels at 72h and 144h. These findings reveal that following injury mitochondrial biogenesis and dynamic processes undergo sustained activation. However, there is a persistent loss of mitochondrial proteins and function after AKI that is associated with differential regulation of transcription within the nucleus and the mitochondria. Funding by NIH GM084147. 751 IDENTIFICATION AND CHARACTERIZATION OF MITOCHONDRIAL TOXICANTS. L. P. Wills, G. C. Beeson, R. Trager, C. Lindsey, Y. K. Peterson, C. C. Beeson and R. G. Schnellmann. Department of Pharmaceutical and Biomedical Sciences, Medical University of South Carolina, Charleston, SC. Many environmental, pharmaceutical, and industrial compounds negatively affect human health through deleterious effects on mitochondrial function. Mitochondrial toxicity is defined as a decrease in the function and /or number of mitochondria, leading to decreased respiration and energy production. Loss of mitochondrial function can result in organ damage due to cellular injury, apoptosis, or necrosis. Currently there is no database of chemicals that cause mitochondrial dysfunction and there are no reliable methods for predicting mitochondrial toxicity. We hypothesized that discrete toxicophores defined by distinct chemical entities can identify previously unknown and future mitochondrial toxicants. To examine this hypothesis we conducted a novel respirometric screen using primary cultures of 162 SOT 2011 ANNUAL MEETING rabbit renal proximal tubule cells (RPTC) and the Seahorse Biosciences XF analyzer. Primary cultures of RPTC are ideal for this assay because they exhibit mitochondrial function similar to that found in vivo. A total of 1760 compounds, 1280 chemicals from the Sigma Library of Pharmacologically Active Compounds (LOPAC) and a random 480 compound subset from the ChemBridge DIVERSet of 50,000 small molecules, were tested in the screen at a concentration of 5 μM. The screen identified 22 compounds that decrease uncoupled respiration, a stress test for mitochondrial function. The effects of the potential mitochondrial toxicants (0.5-5 μM) on cell viability were examined. Of the 22 compounds tested, six compounds decreased uncoupled respiration prior to cell death. One cluster of toxicants was aligned to identify a preliminary toxicophore of mitochondrial dysfunction. We postulate that this approach will enable the identification of mitochondrial toxicants and the prediction of mitochondrial toxicity for both drug discovery and risk assessment. Supported by T32 CA119945-04 and GM084147. 752 MITOCHONDRIAL GSH STATUS IN COMPENSATORY RENAL HYPERTROPHY DUE TO UNINEPHRECTOMY AND DIABETIC NEPHROPATHY. L. H. Lash, B. Benipal, D. A. Putt and Q. Zhong. Pharmacology, Wayne State University School of Medicine, Detroit, MI. Renal proximal tubular (PT) cells exhibit compensatory cellular hypertrophy after either reductions in functional renal mass or in diabetic nephropathy. We have used both the uninephrectomized (NPX) rat and streptozotocin (STZ)-treated diabetic rat to study the biochemistry and toxicology of compensatory renal hypertrophy. PT cells in both models exhibit increases in rates of mitochondrial respiration and activities of several enzymes (‘hypermetabolic’ state), which is associated with enhanced oxidative stress and results in greater susceptibility to many forms of chemically induced injury. In both models, concentrations of GSH are also elevated in both cytoplasm and mitochondria, suggesting a compensatory response. The mitochondrial GSH pool is determined by function of 2 inner membrane transporters (the dicarboxylate [DIC] and 2-oxoglutarate [OGC] carriers). These are electroneutral exchangers that transport dicarboxylates in exchange for inorganic phosphate or 2-oxoglutarate in exchange for other dicarboxylates, respectively. To determine the source of the elevated levels of mitochondrial GSH, mRNA and protein expression as well as transport activities were characterized. In both models, transport function was clearly increased for both carriers although no differences were found in mRNA expression. In remnant kidney from NPX rats, no differences were found in protein expression of either carrier. In renal mitochondria from diabetic rats, however, while no differences were observed in expression of the OGC, DIC protein levels were substantially higher (~ 2-fold) in samples from diabetic vs. control rats. Hence, although levels of GSH in kidneys are elevated in renal mitochondria from both NPX and diabetic rats, mechanisms underlying the increases differ. In NPX rats, the major mechanism appears to be an increase in mitochondrial dicarboxylate content due to the hypermetabolic state. In diabetes, in contrast, there is also an increase in DIC protein levels, not due to a change in transcription but due to increased protein stability or decreased turnover. 753 THE CYTOPROTECTIVE EFFECT OF N- ACETYLCYSTEINE AGAINST ROS-INDUCED CYTOTOXICITY IS INDEPENDENT OF ITS ABILITY TO ENHANCE GLUTATHIONE SYNTHESIS. F. Zhang, S. S. Lau and T. J. Monks. Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson, AZ. 2,3,5-tris(Glutathion-S-yl)-hydroquinone (TGHQ), a metabolite of hydroquinone (HQ), is toxic to renal proximal tubule epithelium cells. TGHQ retains the ability to redox cycle and create an oxidative stress. Consequently, we determined whether the antioxidant, N-acetylcysteine (NAC) could protect HK-2 cells from TGHQinduced toxicity to assist in elucidating the contribution of reactive oxygen species (ROS) in TGHQ-induced toxicity. NAC provided remarkable protection against TGHQ-induced toxicity to human kidney proximal tubule epithelial cells (HK-2). NAC almost completely inhibited TGHQ-induced cell death, mitochondrial membrane potential collapse as well as ROS production. NAC also attenuated TGHQ-induced DNA damage, and the subsequent activation of PARP and ATP depletion. Moreover, NAC significantly attenuated JNK and p38-MAPK phosphorylation induced by TGHQ. Interestingly, NAC alone markedly increased ERK1/2 activation, and the upstream MEK inhibitor, PD-98059, only partially attenuated this activation, suggesting that NAC can directly activate ERK1/2 activity. However, although NAC is frequently utilized as a GSH precursor, the cytoprotection afforded by NAC in HK-2 cells was not a consequence of increased GSH levels, since inhibition of GSH synthesis with BSO had no effect on NAC-mediated cytoprotection. We speculate that NAC might exert its protective effect in part by directly scavenging ROS and in part via ERK1/2 activation (funding sources: P30ES006694).
754 PLASMA, URINE, AND TISSUE CONCENTRATIONS OF HEXAVALENT CHROMIUM ASSOCIATED ACUTE KIDNEY INJURY IN SPRAGUE-DAWLEY RATS. R. P. Brown 1 , Q. Zhang 1 , D. S. Barber 2 , A. C. Komiyama 1 and P. L. Goering 1 . 1 CDRH, U.S. FDA, Silver Spring, MD and 2 University of Florida, Gainesville, FL. Hexavalent chromium (Cr) is a well-known nephrotoxic agent in both experimental animals and humans. The dose of Cr that produces acute kidney injury (AKI) in experimental animals is well understood; however, dose information is rarely available for humans exposed to Cr, especially in patients with an orthopedic implant made from a Cr-containing alloy. Instead, the concentration of Cr in serum, plasma and/or urine is typically reported in these individuals. Since the histopathology of Cr-induced AKI is similar in rodents and humans, it would be useful to characterize the concentration of Cr in plasma, urine and kidney tissue in rodents associated with the onset on AKI as well as the administered dose that produces these effects. In this study, potassium dichromate was administered to male, Sprague-Dawley rats by a single SC injection in doses of 2.5, 5.0 and 10 mg Cr/kg. Rats were placed in metabolism cages and urine was collected for 18 hrs. Serum biomarkers (BUN and blood creatinine) and urinary renal injury biomarkers (α- GST, GSTYb1, RPA-1, clusterin, KIM-1, NGAL, osteopontin and NAG) were measured. Cr concentrations in plasma, urine and kidney were assessed using ICP- MS. A statistically significant increase in levels of some urinary biomarkers (α-GST, GSTYb1, clusterin, Kim-1, NGAL) was observed following administration of 10 mg/kg which corresponded to increases in blood creatinine (NOAEL = 5 mg/kg). No change was seen in levels of BUN, osteopontin, or RPA-1 at any dose level. The mean urinary Cr concentration (n=4) was 0.01, 17.64 and 38.56 μg/ml in control, NOAEL and LOAEL group rats, respectively. Levels of Cr in tissue and plasma also exhibited a dose-dependent increase. Since data on the dose of Cr associated with AKI are available in rats but not humans, and data on the concentration of Cr in various matrices are readily available in humans but not rats, these data provide a means to compare the interspecies effects of Cr on the kidney. 755 COVALENT MODIFICATIONS OF KIDNEY PROTEINS BY S-(1, 2-DICHLOROVINYL)-L-CYSTEINE SULFOXIDE (DCVCS): IN VITRO CHARACTERIZATION USING N- BIOTINYL-DCVCS (NB-DCVCS). R. M. Irving 1 , M. S. Brownfield 2 and A. A. Elfarra 1, 2 . 1 Molecular and Environmental Toxicology Center, University of Wisconsin-Madison, Madison, WI and 2 Department of Comparative Biosciences, University of Wisconsin-Madison, Madison, WI. DCVCS is a reactive electrophile and potent nephrotoxicant generated by the oxidative metabolism of the trichloroethylene metabolite S-(1,2-dichlorovinyl)-L-cysteine (DCVC). DCVCS can covalently modify macromolecules, a property that likely plays a role in its potent nephrotoxicity. In this study, biotin-tagged DCVCS (NB-DCVCS) was synthesized and its reactivity toward glutathione (GSH) and kidney proteins was characterized. When NB-DCVCS was incubated at physiological conditions (pH 7.4, 37°C) with GSH (3:10 molar ratio), four covalent adducts were detected by HPLC and characterized by ESI-MS as monoadducts resulting from Michael addition-elimination reactions (addition of GSH followed by elimination of HCl) between NB-DCVCS and GSH. The half-lives of the two NB- DCVCS diastereomers in the presence of GSH were 19.2 and 42.3 minutes, whereas the half-lives for the DCVCS and N-acetyl DCVCS diastereomers were 19.4 and 3.8 minutes, and 9.9 and 23.1 minutes respectively. When rat kidney cytosol was incubated with 312.5 nM to 10 μM NB-DCVCS for 3 hours at 37°C and immunoblotting was used to detect the biotin tag, a dose-dependent increase in signal with different molecular weights was observed, demonstrating that NB-DCVCS covalently binds to multiple kidney proteins. These results provide the first compelling evidence that DCVCS can form adducts with kidney proteins. Furthermore, these studies indicate that this novel reactive electrophilic probe, derived from a known nephrotoxicant, shows promise as a useful reagent for future studies on characterization of the covalent modification of proteins by nephrotoxic cysteine S-conjugates. (Supported by NIH RO1 DK 044295 and NIEHS T32-ES-007015) 756 ZINC DEFICIENCY EXACERBATES DIABETES- INDUCED RENAL OXIDATIVE DAMAGE, INFLAMMATION, AND FIBROSIS. B. Li 1, 2 , L. Miao 2 and L. Cai 1 . 1 University of Louisville, Louisville, KY and 2 Nephrology, Jilin University, Changchun, jilin, China. Zinc (Zn) as an essential trace element has numerous physiological functions, particularly as an antioxidant to protect the cells and organs against various oxidative damages. However, Zn deficiency often occurs in the patients with diabetes; what is the effect of Zn deficiency on diabetic kidney has not been addressed. The purpose of the present study was to examine the effects of Zn deficiency on diabetes-induced renal oxidative damage, inflammation and fibrosis in streptozotocin (STZ)induced type 1 diabetic mice. Type 1 diabetes was induced in FVB mice treated with multiple low doses of STZ at 50 mg/kg body weight daily for five days. Five days after the last injection of STZ, STZ-treated mice with hyperglycemia and agematched normal mice were treated with and without Zn chelator, TPEN at 5 mg/kg daily for four months. Renal oxidative damage, inflammation and fibrosis in these mice were examined by histopathological observation, Naphthol AS-D Chloroacetate esterase assay, immunofluorescent staining, and Western blotting assay. Results: Chronic treatment with TPEN for four months significantly decreased systemic Zn levels. Renal oxidative damage and inflammation were significantly increased in TPEN/diabetic group compared to group with diabetes or TPEN alone, shown by increased protein nitration and lipid oxidation, and infiltrated inflammatory cells in the kidney with increased expression of inflammatory mediators, plasminogen activator inhibitor (PAI)-1 and intercellular adhesion molecule (ICAM)-1. In the TPEN/diabetic group, renal fibrosis was also significantly evident compared to those in TPEN or diabetic group, reflected by increased collagen accumulation in glomerulus messangial area and renal expression of pro-fibrotic mediator connective tissue growth factor. These results indicated that Zn deficiency significantly enhanced diabetes-induced renal oxidative damage and inflammation, resulting in severe renal fibrosis. This study suggests that diabetic patients should prevent their Zn deficiency in order to avoid the acceleration of diabetic renal injury. 757 ROLE OF OXIDATIVE STRESS INDUCED BY CHROMATE IN THE ACTIVATION OF MAPK IN NRK- 52E CELLS. L. Arreola-Mendoza 1, 2 , J. L. Reyes 3 , E. I. Sanchez 3 and L. M. Del Razo 2 . 1 Biosciences and Engineering, CIIEMAD-IPN, Mexico D.F., Mexico, 2 Toxicology, Cinvestav-IPN, Mexico D.F., Mexico and 3 Physiology & Biophysics, Cinvestav-IPN, Mexico D.F., Mexico. Chromate (Cr6+), the most toxic form of this metal, is widely used in industrial processes and is widespread found as environmental toxicant. Renal toxicity has been described in chromium-exposure and antioxidant administration prevents these deleterious effects. In the biological systems reduction of Cr6+ to Cr3+ results in the formation of reactive intermediates such as reactive oxygen species (ROS) leading to oxidative tissue damage and cellular injury. On the other hand, in lung epithelial cells, ROS are mediators of cell signaling. Cr6+ leads to activation of c- Jun N-terminal kinase (JNK), p38 and extracellular signal regulated kinase (ERK), members of the mitogen-activated protein kinases (MAPKs). In this study we evaluate the role of ROS generation by Cr6+ exposure in the activation of JNK, p38, and ERK1/2 in NRK-52E, cellular line derived from renal proximal tubule. Cells viability was evaluated in a dose-response curve (range of 10 to 200 μM) by trypan blue and lactate dehydrogenase release (LDH). Thereafter, cellular culture (7 days of growing) was exposed to Cr6+ (100 μM) at 5, 10 and 30 min and 1 and 6 h, with or without alpha-tocopherol treatment (25 μM). Phosphorilation of MAPKs was evaluated by Western blotting and ROS level by DCFDA (5’, 6’ –chloromethyl -2’ 7’-dichlorofluorescin diacetate). Cr6+ induced time-depending ERK1/2 activation, as indicated by phosphor-ERK (1/2), from 5 min, p38 phosphorylation was slightly detectable only at 6 hours without change in the activation of JNK. Cr6+ induced ROS generation since 5 min until 1 h, while at 6 h ROS level was as a control. ROS were induced in the cells simultaneously treated with alpha-tocopherol only at 5 and 10 min, and notably in presence of alpha-tocopherol ERK1/2 was not activated. Our results showed a clear relationship between the induction of ROS and the activation of ERK1/2 in NRK-52E. (Funding by CONACYT Mexico) 758 ALUMINUM CITRATE AND COM: MECHANISMS FOR DECREASED RENAL INJURY IN A RAT MODEL OF ETHYLENE GLYCOL POISONING. L. M. Besenhofer, M. C. McLaren and K. E. McMartin. Pharmacology, Toxicology, and Neuroscience, Louisiana State University Health Sciences Center - Shreveport, Shreveport, LA. Calcium oxalate monohydrate (COM) crystals are responsible for the kidney injury associated with ethylene glycol (EG) exposures. In cases where anti-metabolite therapy is delayed, long-term kidney injury is common and current treatments do not address the mechanism (accumulation of COM). Our in vitro studies have shown that aluminum citrate, uniquely among citrate salts, blocks the toxicity in human proximal tubule cells. This study was designed to evaluate the efficacy and mechanism of action of aluminum citrate in a rat model of EG poisoning. Wistar rats were placed into five treatment groups including control (water at time 0), EG (6 g/kg, gavaged at time 0), aluminum citrate, EG + aluminum citrate and EG + SOT 2011 ANNUAL MEETING 163
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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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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
Page 377 and 378:
model of APAP metabolism and glutat
Page 379 and 380:
logically & morphologically similar
Page 381 and 382:
posure, blood chemistry was analyze
Page 383 and 384:
elated to oxidative stress by measu
Page 385 and 386:
ostasis), but work is needed to tra
Page 387 and 388:
tokine products during carcinogenes
Page 389 and 390:
ways as chemical stressors and, the
Page 391 and 392:
toxicity of nanomaterials relates s
Page 393 and 394:
1815 MEASURING COMPOUND SELECTIVITY
Page 395 and 396:
1825 EFFECTS OF METABOLISM BY INTES
Page 397 and 398:
cyanoacetic acid increased 2-3 fold
Page 399 and 400:
1845 IS THE PROMISCUITY OF THE ARYL
Page 401 and 402:
crorarray analysis. RT-PCR results
Page 403 and 404:
are a family of phase-II biotransfo
Page 405 and 406:
ous labs. As a result of positive s
Page 407 and 408:
down the doses may produce more tox
Page 409 and 410:
spectively. Below 100 mg/l of gemfi
Page 411 and 412:
1900 GENERATION OF PRECISION CUT LI
Page 413 and 414:
iomarkers or observation of lesions
Page 415 and 416:
creased reticulocytes and lymphocyt
Page 417 and 418:
statistically significant interacti
Page 419 and 420:
monize sample preparation and analy
Page 421 and 422:
NPC and sinonasal cancer in neighbo
Page 423 and 424:
showed incidences of lung and nasal
Page 425 and 426:
utylbenzenes, exhibited most simila
Page 427 and 428:
1975 DIFFERENTIAL MODULATION OF CYP
Page 429 and 430:
organic As to MMA(V) and a lower ca
Page 431 and 432:
ole in invasion and metastasis of c
Page 433 and 434:
3T3-L1 cells to low-levels of arsen
Page 435 and 436:
2011 IDENTIFICATION OF A NOVEL VX M
Page 437 and 438:
This work was supported by Cooperat
Page 439 and 440:
2029 EFFICACY OF ENDOTRACHEAL ADMIN
Page 441 and 442:
Diazepam injections and its combina
Page 443 and 444:
2047 ESTERASE ACTIVITIES AND HEMOST
Page 445 and 446:
nanoparticle-induced toxicity progr
Page 447 and 448:
house, were iv infused into rats ov
Page 449 and 450:
een explored. This study investigat
Page 451 and 452:
croscopic analysis revealed that on
Page 453 and 454:
egg yolk collected from turtles inh
Page 455 and 456:
consistency of results in both expe
Page 457 and 458:
2111 CYTOCHROME P450 3A5 GENOTYPE I
Page 459 and 460:
esidues of organophosphates or thei
Page 461 and 462:
manganism. Recent work from our lab
Page 463 and 464:
Aβ1-40 in CSF and hippocampus in P
Page 465 and 466:
2147 CATALASE MANIPULATIONS MODIFY
Page 467 and 468:
ation based on real-world exposure
Page 469 and 470:
NPs. Aggregation of citrate-stabili
Page 471 and 472:
2175 THE ROLE OF SURFACE CHEMISTRY
Page 473 and 474:
seen rapid uptake in biological ima
Page 475 and 476:
effect on uterine weight or vaginal
Page 477 and 478:
dicating widespread exposure. While
Page 479 and 480:
components into the liver parenchym
Page 481 and 482:
2223 ISOLATION AND DETECTION OF RIC
Page 483 and 484:
stored (-20 celsius degree). The co
Page 485 and 486:
2241 DDA, A BIOMARKER FOR ENVIRONME
Page 487 and 488:
2249 INTERACTION BETWEEN DIETARY SE
Page 489 and 490:
2258 PHARMACOKINETICS, EXCRETION BA
Page 491 and 492:
2267 SENSITIVE AND SPECIFIC FLUORES
Page 493 and 494:
2276 METABOLISM AND DISPOSITION OF
Page 495 and 496:
ment of hypertension in companion a
Page 497 and 498:
for the propyl series can be used f
Page 499 and 500:
2304 IN VITRO EXPOSURE AND EVALUATI
Page 501 and 502:
2313 THE SYNERGISTIC EFFECT OF SODI
Page 503 and 504:
genes that play a crucial role in M
Page 505 and 506:
2330 THE ROLE OF TRANSFORMING GROWT
Page 507 and 508:
ined following up to 96 h continuou
Page 509 and 510:
effect doses obtained with the rat
Page 511 and 512:
diated transcriptional response of
Page 513 and 514:
docrine disruptor activities of EDC
Page 515 and 516:
individuals. Week 6 results were qu
Page 517 and 518:
functionality of photosystem II and
Page 519 and 520:
wild mice (Mus musculus) from areas
Page 521 and 522:
2406 TOXICITY AND BIOACCUMULATION O
Page 523 and 524:
Isocitric acid is the acid in the h
Page 525 and 526:
2425 EFFECTS OF FUMONISINS IN ETHAN
Page 527 and 528:
centration(μg/g) were: 5.1-95.3; 2
Page 529 and 530:
2445 AUTOPHAGY IN DEVELOPMENT: A LI
Page 531 and 532:
sures to inhaled Mn in dust. Nevert
Page 533 and 534:
2466 CRITICAL EVALUATION OF ANIMAL
Page 535 and 536:
elationships predict that resting r
Page 537 and 538:
2489 COMPARATIVE TOXICITY OF BIODIE
Page 539 and 540:
2497 TRANSCRIPTIONAL REGULATION OF
Page 541 and 542:
2506 TOXICOLOGICAL CONSIDERATIONS O
Page 543 and 544:
launched with the aim of developing
Page 545 and 546:
forms mRNA expression levels were a
Page 547 and 548:
2534 CUTANEOUS WOUND HEALING IN THE
Page 549 and 550:
wells (0, 1, 5, 10, 25, 50, 100, an
Page 551 and 552:
2553 AN ORGANOTYPIC MICROLIVER PLAT
Page 553 and 554:
serum-free media. At 24 hrs, the gr
Page 555 and 556:
2572 INCREASED ARSENIC BIOACCESSIBI
Page 557 and 558:
nology to develop improved methods.
Page 559 and 560:
tuna, swordfish, or mako shark (3.5
Page 561 and 562:
nificantly reduce circulating thyro
Page 563 and 564:
grouped into 9 observation periods
Page 565 and 566:
histopathological or biochemical ev
Page 567 and 568:
exhibited a hyperactive phenotype,
Page 569 and 570:
the search of effective drugs for e
Page 571 and 572:
2644 COVALENT BINDING OF 14 C 2-MET
Page 573 and 574:
aries targeting all transcription f
Page 575 and 576:
(p 9 weeks) and CSC phenotype acqui
Page 577 and 578:
2673 IMMUNE-MEDIATED VASCULAR INJUR
Page 579 and 580:
for risk identification and charact
Page 581 and 582:
to control toxicant delivery in tob
Page 583 and 584:
Author Index (Continued) The numera
Page 585 and 586:
Page 587 and 588:
Page 589 and 590:
Page 591 and 592:
Page 593 and 594:
Page 595 and 596:
Page 597 and 598:
Page 599 and 600:
Page 601 and 602:
Page 603 and 604:
Page 605 and 606:
Page 607 and 608:
Page 609 and 610:
Page 611 and 612:
Keyword Index (Continued) Arsenite
Page 613 and 614:
Keyword Index (Continued) Covalent
Page 615 and 616:
Keyword Index (Continued) flow cyto
Page 617 and 618:
Keyword Index (Continued) innate im
Page 619 and 620:
Keyword Index (Continued) nanoparti
Page 621 and 622:
Keyword Index (Continued) preservat
Page 623 and 624:
Keyword Index (Continued) Thrombocy
Page 625 and 626:
Toxicological Sciences The Official
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