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effects of MB on erythrocytes with freshly isolated human erythrocytes, in an effort to elucidate the mechanism underlying the MB-induced erythrocyte decrease. Incubation of MB did not induce erythrocyte hemolysis, indicating that it does not induce direct erythrocyte toxicity. However, phosphatidylserine (PS) exposure on erythrocyte membrane and spherocytic shape change as well as microvesicle (MV) generation, important factor in erythrophagocytosis increased significantly by MB. Reactive oxygen species (ROS) generation, decreased glutathione levels and subsequent depletion of protein thiol and ATP levels were shown to underlie the mechanism of MB action on erythrocyte. Consistent with these findings, the activity of flippase was inhibited while scramblase was enhanced by MB, which could maintain and expose PS on erythrocyte membrane, respectively. Co-incubation with macrophage and MB-treated erythrocyte in in vitro showed increased phagocytosis, suggesting that the removal of erythrocyte by macrophage can be occurred indeed. Importantly, these PS exposure and erythrophagocytosis by MB were confirmed in in vivo rat model, with the same protocol as the preclinical safety test. In conclusion, these results suggest that MB-induced decreased erythrocyte count was mediated through the PS exposure and erythrophagocytosis. Furthermore, with this clarification of toxic mechanism, we believe that the novel solution can be provided from it. 1218 INTRACELLULAR BAX TRAFFICKING: A DETERMINANT OF CELL DEATH? S. Krishnan 1 , W. Miller 1 , M. Gill 2 and J. Perez-Polo 1 . 1 University of Texas Medical Branch, Galveston, TX and 2 Northwestern University, Chicago, IL. Sponsor: J. Ward. Brain damage due to neonatal hypoxia-ischemia (HI) is a major cause of morbidity and mortality in infants. Our long-term goal is to characterize HI-induced intracellular localization of Bax in order to develop intervention strategies that may prevent permanent damage in the developing brain of infants. Here we measured Bax multi-organelle localization after in vivo HI-injury and after 100% O 2 rescuscitation and its correlation with organelle-specific cell death signaling. In addition to examining HI- and HHI- treated cortical Bax protein, we used rotenone-treated P5 neuronal cortical cultures, differentiated PC12 and SY5Y cells to better characterize the role of Bax shuttling in cell death signaling cascades. In particular, we examined the role of Bax phosphorylation after apoptotic and necrotic-like cell death stimuli. We asked whether HI-dependent differential phosphorylation of Thr 167 and Ser 163 residues determines Bax intracellular localization. Neonatal (P7) brain HI induces intracellular translocation of Bax to the nucleus, mitochondria, and ER, where it triggers activation of cell death signaling cascades. When compared to HI-treated rat pups, we found that 100% O 2 resuscitation of HI-treated (HHI) rat pups increases HI-induced ER Bax levels, ER-mediated cell death signaling, and lesion volume likely due to an increase in necrotic-like cell death, triggering an over-activation of inflammatory signaling. We also observed an increase in p-Bax Thr167 in the nucleus of cortical tissue at 1 hour after HI when compared to shams. This suggests a role for phosphorylation in the translocation of Bax to the nucleus. Understanding the mechanisms of Bax translocation will aid in the rational design of specified therapeutic strategies which could potentially involve altering Bax subcellular redistribution to decrease the irreversible trauma resulting from a prolonged inflammatory response. Supported in part by NIEHS training grant award T32 ES007254; NICHD grant HD039833 and grant 8540 from the Shriner’s Children’s Hospital. 1219 QUERCETIN INDUCES TUMOR-SELECTIVE APOPTOSIS THROUGH DOWN-REGULATION OF MCL-1 AND ACTIVATION OF BAX. S. Cheng 1 , G. Chen 2 , J. Luo 2 and X. Shi 1 . 1 University of Kentucky, Lexington, KY and 2 University of Kentucky, Lexington, KY. Quercetin is a promising anti-tumor agent that induces apoptosis in a variety of tumor cells. Here we report that administration of quercetin in human leukemia cells resulted in a marked release of cytochrome c and smac/diablo, cleavage/activation of caspase 8, 9, 7 and 3, and apoptosis. Pronounced apoptosis was also observed in blasts from patients with different leukemia types but no in normal blood peripheral mononuclear cells. These events were accompanied by myeloid cell leukemia-1 (Mcl-1) down-regulation, most likely through a translational mechanism, in association with diminished eIF4E phosphorylation. Ectopic expression of Mcl-1 but not Bcl-2 and Bcl-xL reduced quercetin-induced cytochrome c release and cell death. In contrast, interruption of Mcl-1 by siRNA enhanced quercetin’s ability to stimulate quercetin’s lethality. We also found that in response to quercetin, Bax protein underwent conformational changes and then translocation to mitochondrial membrane which caused release of cytochrome c. Treatment with Bax siRNA resulted in a reduction of querctin-induced apoptosis. Bax-negative human prostate cancer DU-145 cells were not sensitive to quercetin treatment and knockout of Bax completely abrogated the activation of caspase 3, cytochrome c release and apoptosis. Data also show that Bax activation was mediated by caspase 8- dependent Bid cleavage and also by Mcl-1 down-expression. However the inhibition of Bax by Mcl-1 was through their indirect interaction. Collectively, these findings demonstrate that quercetin induces Mcl-1 down-regulation and Bax activation, culminating in mitochondrial injury and apoptosis. They also raise the possibility that these events may preferentially occur in leukemia versus normal hematopoietic cells. 1220 ROLE OF EXTRACELLULAR FREE IRON AND MAPK SIGNALING IN SMOKELESS TOBACCO-INDUCED NECROTIC CELL DEATH IN HUMAN ORAL KERATINOCYTE CULTURES. M. W. Fariss 1 , C. Mitchell 2 , A. R. Joyce 2 and D. Farthing 1 . 1 Health and Analytical Sciences, Altria Client Services, Richmond, VA and 2 RemX Specialty Staffing c/o Altria Client Services, Richmond, VA. The use of smokeless tobacco products at the same oral site may result in an acute injury characterized by ulceration and inflammation that is reversible upon elimination of same site use. Previous studies in our laboratory demonstrated that a 3 h exposure of cultures of human oral keratinocytes (HOK) to reference moist smokeless tobacco extracts (STE) leads to necrotic cell death in part through oxidative stress via the activation of MAPK pathways. Using the same cell model system, the present study investigates the role of extracellular free iron and MAPK signaling in STE- and Snus extract (SE)-induced necrotic cell death and oxidative stress. Findings from this study indicate a difference in the ability of STE and SE (at identical concentrations) to induce acute necrotic cell death, ROS production and activation of ASK1 and the JNK 1/2 and p38 MAPK pathways in HOK cultures which correlates with free iron concentrations in the extracts. For example, extracellular free iron levels in STE (29.4 ± 0.5 μM) were elevated as compared with SE (12.7 ± 0.5 μM) and cell culture medium (4.9 ± 0.6 μM). In fact, the observed difference in the acute cytotoxic ability between STE and SE was eliminated by reducing free iron levels in STE to that observed in SE with an iron chelator (deferoxamine) or by increasing the free iron content of SE to that observed in STE. In conclusion, STE leads to cell death in human oral keratinocytes in part through free iron-induced oxidative stress and the activation of ASK1 and the JNK1/2 and p38 MAPK pathways. 1221 HUMAN PRIMARY ALVEOLAR CELL INJURY INDUCED BY CIGARETTE SMOKE. B. Kosmider, H. Chu and R. J. Mason. Medicine, National Jewish Health, Denver, CO. Sponsor: B. Day. Oxidative stress caused by cigarette smoke (CS) directly causes lung injury and cell death in chronic obstructive pulmonary disease. Moreover, many studies show that second-hand smoke can have harmful effects on nonsmokers and even cause them to develop lung cancer and heart disease. The epithelium is the barrier between inhaled air, which contains toxic compounds in cigarette smoke and the underlying tissue. To study CS-induced cell injury we exposed human primary alveolar type II (ATII) cells isolated from deidentified healthy, non-smoker lung donors to cigarette smoke extract (CSE). We also transdifferentiated ATII cells to alveolar type I-like (ATI-like) cells in vitro. We observed induction of apoptosis and necrosis after ATIlike cells and ATII cells exposure for 4h and 24h to CSE using TUNEL assay, acridine orange/ethidium bromide, and Hoechst 33342/propidium iodide double staining. Moreover, we found a concentration- and time dependent increase in Nrf2, HO-1, Hsp70, Fra1 and MAP kinase protein expression in these cells after exposure to CSE. We also observed a nuclear translocation of Nrf2 induced by CSE in ATI-like cells. These results indicate oxidative stress and DNA damage. Furthermore, we observed higher sensitivity of ATI-like cells to CSE than ATII cells. Identification of the pathways whereby CS generates reactive oxygen species and induces apoptosis may further our understanding of the pathogenesis of CS-induced lung disease. This work is supported by a Young Clinical Scientist Faculty Award to Beata Kosmider from the Flight Attendant Medical Research Institute. 1222 INHIBITION OF APOPTOTIC DNA-FRAGMENTATION BY 2, 3, 7, 8-TETRACHLORODIBENZO-P-DIOXIN. M. Chopra 1 , G. Meiss 2 and D. Schrenk 1 . 1 University of Kaiserslautern, Kaiserslautern, Germany and 2 Biochemistry, Justus-Liebig-University, Giessen, Hessen, Germany. Despite not being directly genotoxic, 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) was classified as a class 1 carcinogen by the IARC and is one of the most potent tumor promotors in rodent liver. It has been hypothesized that TCDD promotes tumor growth by inhibiting apoptosis of initiated cells. Therefore, we tested which targets along apoptotic pathways are affected by TCDD treatment of liver cells. Primary rat hepatocytes were irradiated with UV-C light to induce apoptosis. After subsequent treatment with TCDD, up-stream apoptotic events like prote- 260 SOT 2010 ANNUAL MEETING
olytic caspase activation, caspase-activity and cleavage of inhibitor of caspase-activated DNase (ICAD) were not inhibited whereas the extent of apoptotic chromatin condensation and DNA-fragmentation was decreased. Using the arylhydrocarbon receptor (AhR) antagonist CH-223191, the inhibiting effect of TCDD towards apoptotic chromatin condensation and fragmentation could be linked to AhR activation. Next, we investigated whether TCDD directly or indirectly influenced the activity of exogenous caspase-activated DNase (CAD). TCDD did not affect CAD-activity towards naked genomic DNA. Neither was CAD-activity modulated towards isolated nuclei treated with TCDD for 24 h. Furthermore, activity of CAD towards nuclei from cells irradiated with UV-light and treated subsequently with TCDD for 1 h was not influenced. It appears plausible that TCDD inhibits apoptotic DNA-cleavage by some unknown mechanism in order to retain genomic integrity, allowing the cell to deal with xenobiotics despite an initiation of apoptosis. These cells could recover from an apoptotic insult, harbouring genetic aberrations. This could explain the tumor promoting potential of TCDD and might be an underlying mechanism for other tumor-promotors which induce xenobiotic metabolism. 1223 LOCALIZATION OF ENDONUCLEASE G AND FRAGMENTED DNA DURING ACETAMINOPHEN LIVER INJURY IN MICE. N. Braman 1 , E. O. Apostolov 1 , L. Cortez 1 , J. Hinson 1 and A. G. Basnakian 1, 2 . 1 University of Arkansas for Medical Sciences, Little Rock, AR and 2 Central Arkansas Veterans Healthcare System, Little Rock, AR. Acetaminophen (APAP) is the most common cause of acute liver failure in the United States. The morphological damage by APAP observed in the liver is centrilobular necrosis. It is associated with DNA fragmentation mainly by endonuclease G (EndoG) as determined by nuclear TUNEL assay, which is a surrogate method for apoptosis detection. Leakage of TUNEL-positive DNA fragments into the cytoplasm (cytoplasmic TUNEL) has been observed in some studies and interpreted as a sign of necrosis. In the present study, we localized EndoG by immunostaining and tested whether quantification of nuclear and cytoplasmic TUNEL may be used as a universal assay for APAP-induced liver cell damage that would allow simultaneous detection of apoptosis and necrosis in the same cell. Mice were injected with APAP (300 mg/kg IP) and liver samples were taken at varying periods of time within 12 hours. There was no significant induction of EndoG during this time period, while some nuclear translocation of EndoG was observed. The treatment resulted in the increase of TUNEL-positive cells around the central veins between 2 and 12 hours after APAP injections. At the 2-hour time point, the TUNEL was mainly nuclear suggesting cell death by apoptosis. By 4 hours, TUNEL-positive material significantly leaked to cytoplasm, where it reached a maximum of 22% of total TUNEL, indicating the appearance of necrosis possibly associated with quick partial destruction of the nuclear membrane. At later time points, both nuclear and cytoplasmic TUNELs decreased suggesting leakage of plasma membrane due to further development of necrosis. These data provide evidence that apoptosis and necrosis coexist in liver during APAP injury, and that measurement of nuclear and cytoplasmic TUNEL may be a useful method for the assessment of apoptosis and necrosis coexisting in individual cells in vivo, and for measuring the progression of toxic liver injury. 1224 ENDONUCLEASE G MEDIATES ENDOTHELIAL TOXICITY INDUCED BY CISPLATIN. Y. Apostolov 1 , D. Ray 1 , A. Savenka 1 and A. Basnakian 1, 2 . 1 Pharmacology/Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR and 2 Central Arkansas Veterans Healthcare System, Little Rock, AR. Cisplatin is one of the most frequently used drugs for the treatment of advanced breast cancer, lung cancer, testicular cancer and leucosis. It is known to induce endothelial cell injury, which may lead to thrombotic complications and arterial hypertension, and significantly contribute to cardiac and kidney toxicities. Endothelial injury is a key mechanism in pathogenesis of the chemotherapy-induced cardiovascular complications. The mechanisms of endothelial cell injury induced by cisplatin are unknown. Our recent studies strongly suggest that endonuclease G (EndoG), a cytotoxic mitochondrial enzyme, serves as a universal key molecule in caspase-independent apoptosis and autophagy in various in vitro and in vivo cell injuries induced by cisplatin. In the current study, we hypothesized that EndoG mediates cisplatin endothelial toxicity. We first demonstrated that cisplatin in therapeutic doses causes injury of human coronary artery endothelial cells (HCAECs) in vitro as determined by LDH release assay. EndoG expression measured by cell ELISA showed that cisplatin-treated HCAECs express significantly more EndoG than untreated cells. Targeted inhibition of EndoG by siRNA led to above 70% protection of HCAECs treated with cisplatin (25 uM). To determine whether inactivation of EndoG is protective to endothelial cells in vivo, EndoG knockout (KO) and control wild-type mice were subjected to single injection of cisplatin (6 mg/kg, IV). The number of rescued endothelial cells in aorta was evaluated using quantitative microscopy, while floating (dead) endothelial CD31-positive endothelial cells in blood were quantified using flow cytometry. These experiments showed that endothelial cells in KO mice are significantly protected from cisplatin injury. Therefore our data suggest that EndoG plays causative role in cisplatin-induced endothelial toxicity and may potentially be used as a target for support therapy in order to prevent its cardiovascular complications. 1225 1, 1-BIS(3’-INDOLYL)-1-(P-SUBSTITUTED PHENYL)METHANES ACTIVATE MITOCHONDRIAL PERMEABILITY TRANSITION PORE-MEDIATED APOPTOSIS IN BOTH COLON AND PANCREATIC CANCER CELLS. P. Lei, S. Zhang, K. Kim, X. Liu and S. Safe. Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, TX. 1,1-Bis(3’-indoly)-1-(p-substituted phenyl)methanes (C-DIM) activate peroxisome proliferator-activated receptor gamma and nerve growth factor-induced Balpha (Nur77) and induce receptor-dependent and receptor-independent apoptosis in cancer cells and tumors. In this study, we investigated the activation of apoptosis in colon and pancreatic cancer cells by p-bromo substituted analogs (DIM-C-pPhBr). DIM-C-pPhBr activated the extrinsic and intrinsic apoptotic pathways and decreased mitochondrial membrane potential (MMP) in both colon and pancreatic cancer cells. The mitochondrial permeability transition pore (MPTP) blocker cyclosporin A (CsA) inhibited DIM-C-pPhBr -induced apoptosis and decrease of MMP, indicating that DIM-CpPhBr-induced apoptosis is related to MPTP opening. C-DIM-pPhBr also activated the c-Jun NH(2) kinase (JNK) pathway, resulting in the induction of CCAAT/enhancer-binding protein homologous protein, death receptor 5, and the extrinsic apoptotic pathway. Inhibitor studies showed that CsA, reactive oxygen species (ROS) inhibitor NAC and JNK inhibitor SP600125 blocked the JNK stress pathway in C-DIM-pPhBr treated cells, indicating that C- DIM-pPhBr-activated JNK stress pathway is MPTP- and ROS-dependent. Further analysis showed that C-DIM-pPhBr induced ROS generation which is also blocked by both CsA and NAC, indicating MPTP opening playing a role in C-DIM-pPhBr induced ROS generation. Moreover, western blotting analysis showed that CsA inhibited the activation of caspase-8 and caspase-9 while NAC only blocked the activation of caspase-8. Thus, C-DIM-pPhBr induced MPTP opening in both colon and pancreatic cancer cells, resulting in activation of the intrinsic apoptotic pathway and ROS generation. Subsequent activation of the JNK and the extrinsic apoptotic pathway was also dependent on opening of the MPTP complex and induction of ROS. 1226 P62 SEQUESTERS KEAP1 INTO AUTOPHAGOSOMES, PREVENTING THE KEAP1-DEPENDENT UBIQUITINATION AND DEGRADATION OF NRF2. A. Lau, X. Wang, F. Zhao, N. F. Villeneuve, T. Jiang, T. Wu, Z. Sun and D. D. Zhang. Pharmacology and Toxicology, University of Arizona, Tucson, AZ. Protein degradation is tightly regulated by two major degradation machineries, the ubiquitin-proteasome system (UPS) and the autophagy-lysosome pathway (ALP). Here, we report the cross-talk between these two systems through p62. We demonstrate that activation or inhibition of autophagy increases the formation of autophagosomes and thus, suppresses the degradation of a well-characterized UPS substrate, Nrf2, in a highly specific manner. Under basal conditions, Nrf2 is ubiquitinated by the Keap1-Cul3-E3 ubiquitin ligase complex and targeted to the 26S proteasome for degradation. In this current study, we show that upregulation of endogenous p62, or ectopic expression of p62, sequesters Keap1 into autophagosomes through direct interaction resulting in the inhibition of the Keap1-mediated Nrf2 ubiquitination and subsequent Nrf2 degradation by the UPS. In contrast, overexpression of mutated p62, which loses its ability to interact with Keap1, had no effect on Nrf2 stability. Moreover, overexpression of p62 had no effect on the stability of other UPS substrates, including IκBα, c-Jun, and cyclin A, B1, and D1, demonstrating its specificity for Nrf2. These findings contribute to our understanding of how autophagy may regulate specific UPS substrates. 1227 AUTOPHAGY: A KEY MECHANISM IN ARSENITE- INDUCED CYTOTOXICITY IN HUMAN LYMPHOBLASTOID CELL LINES. A. M. Bolt, R. M. Byrd and W. T. Klimecki. Pharmacology and Toxicology, University of Arizona, Tucson, AZ. Arsenic is a ubiquitous environmental toxicant that is associated with a range of diseases and has a complex set of molecular targets in diverse tissue types, making it difficult to identify the mechanisms and pathways involved in arsenic-induced cytotoxicity. One commonality in arsenic toxicology is its ability to induce apoptosis SOT 2010 ANNUAL MEETING 261
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The Toxicologist Supplement to Toxi
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The Toxicologist Supplement to Toxi
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1 BIOLOGICAL PATHWAY ANALYSIS: AN I
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11 ICH INITIATIVES FOR CONDUCTING P
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models. Experimental approaches and
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30 SILICA AND ASBESTOS IMMUNOTOXICI
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40 NONCANCER TOXICITY POTENTIAL AT
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ased products for patient administr
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nase regulates Hsp27-induced reorga
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exposure resulted in splenomegaly.
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We investigated the effect of imati
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well plate prevented free cell move
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98 DERIVING SIGNATURES OF IN VIVO T
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sulfate, cinnamic aldehyde, 2,4-din
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The final product will be a system
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mercially available STP brands by m
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for six weeks, with 10 mg/kg azoxym
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eceived RES post-TCDD exposure when
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morigenesis. Knocking down of JARID
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163 MICROPET IMAGING OF [18F]-DFNSH
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These results are comparable to tha
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activity as assessed by lever press
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for measured physico-chemical param
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199 DEVELOPMENT OF A MULTIPARAMETER
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To cause PLD, a drug needs to enter
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In contrast to the parent PBDEs and
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transiently transfected HEK 293 cel
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TCDD exposure, 24 h prior to a 20 %
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244 NON-ADDITIVE EFFECTS OF PCB153
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253 COMPARISON OF MIXTURE TOXICITY
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two cerium oxide nanoparticles of v
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271 SIZE-DEPENDENT EFFECTS OF TUNGS
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adigms such as Tox 21 and Toxcast,
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QDs with emission maximum at 800nm
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Cleveland, while others were found
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without the need of animal testing.
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Conclusions: These results are cons
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ing oxime reactivation and organoph
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335 A NON-OXIME IMPROVES SURVIVAL I
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alties suffer from permanent lung i
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ies have established inflammatory b
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363 GENETIC VARIATION IN ISOGENIC M
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372 EVALUATING THE BIOLOGICAL INTER
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dose of 1/20 LD50 (400 mg/kg.bwt) f
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median CR-adjusted isoflavone conce
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data indicate that AhR deletion pro
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February 2006). The rabbit is one o
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tal neurotoxicity (DNT) test (OECD
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of selected microorganisms that are
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BVI. Histopathological analysis was
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446 MOLECULAR CLONING AND CHARACTER
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portant in predicting risk. CYPs 1A
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ats, which involves metabolic activ
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473 BOVINE CORNEAL OPACITY AND PERM
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482 TYPE III DEIODINASE (D3) IS PRO
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tancy evaluation and ranking of bat
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501 CHARACTERIZATION OF ESTERASE, G
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510 REDOX CYCLING BY ENDOGENOUS 2-
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prostate cancer cells. All 8 BEL de
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metallic nickel nanoparticles. Acti
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variety of more or less reactive ch
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550 QUALIFICATION STRATEGIES-GENOTO
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ferentiation, and 3) how mixtures o
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572 LOW-CHRONIC ARSENIC EXPOSURE: E
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582 IDENTIFICATION OF SENSITIVE URI
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duced by the genetic outcross of fe
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fects of new compounds are equally
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acterize the current state of the s
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620 CHARACTERIZATION OF POTENTIAL I
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ways. Moreover, both MAP kinase and
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641 POPS IN THE U.S. POPULATION AND
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studies such as the NCS, consider h
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the beginning of the academic caree
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trophil infiltration, a significant
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tactic response and optokinetic res
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usually high spontaneous PIG-A MFs.
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699 PROMUTAGEN ACTIVATION AND P450
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oxodG in bone marrow, spleen, kidne
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718 GENOTOXICITY OF ORGANIC EXTRACT
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ment were 18.0 and 4.5 nM for BEAS-
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strongest activation of nuclear fac
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746 MACROPHAGE INHIBITORY CYTOKINE-
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screening of cell migration. High-c
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dase inhibition). In contrast, inhi
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mice; the decrease was more pronoun
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Markers of oxidative damage reached
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793 PULMONARY RESPONSE, OXIDATIVE S
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cilitate clinical and industrial ap
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sion of p-p38, p-p53, p21 and cycli
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821 KIDNEY INJURY MOLECULE-2 GENE D
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commercial applications, and have b
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developmental effects. The residual
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strand breaks in an in vitro model
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etate (immunotoxicity). 2,4-D was t
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867 MELATONIN AMELIORATES CYCLOPHOS
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pharmacokinetic (PBPK) models. Ten
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of radiolabeled Mn (carrier-free 54
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893 UNVEILING ASSOCIATIONS BETWEEN
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using area under the concentration
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912 COMMERCIAL FISH DIETS INDUCE VI
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922 A STUDY OF PHOTOTOXICITY FOLLOW
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from 0.1 to 2.9 g/L (saturated vapo
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vasive method for assessing several
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950 ARSENITE DOWN-REGULATES THE CAR
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inflammatory signaling is altered b
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treated wood. Seventy-five of 132 w
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Page 245 and 246: zebrafish cells were first exposed
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Page 295 and 296: 1368 OVERVIEW OF THERAPEUTIC VACCIN
Page 297 and 298: to a bovine adrenal cortical epithe
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1;akt-2 double mutant and pdk-1 mut
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jury effects when compared to contr
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tude than equivalent oral doses. Af
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cells; and increased iNOS and MCP-1
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B6.Cg-Kit W-sh mice. These findings
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1511 STATIN-TREATMENT EFFECTIVELY R
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1520 EFFECT OF INHALATION EXPOSURE
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numbers of IFN-γ producing cells w
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These data indicate that TCDD treat
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esponse to allogenic cells, where P
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larly suppressed LPS-induced TNF-α
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1565 INFLUENCE OF EXPOSURE ROUTE AN
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veloping animals to adverse effects
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the observed CL values were 0.07 L/
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which is most relevant for potentia
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tive impairment, suggesting that ox
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1611 AN IN VITRO METABOLOMICS APPRO
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Expression of the β6 integrin (Itg
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ats (10 μg/kg TCDD). Here we repor
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at liver slices and how the metabon
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with gender differences in AUC and
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oxetine (30 mg/kg reduced to 15 mg/
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eleased from necrotic cells where i
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plants, they are present in surface
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ferentiation (quantitative in-cell
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control for macrophage activation).
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to 0.5μg/ml. Minimal inhibitory co
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lines tested. Given that dex and AT
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tion in the absence of an immune re
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treated rats had lower calcium load
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1740 PROFILING COMPOUNDS WITH CARDI
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dothelial cells confirmed caveolin-
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1758 GINKGO BILOBA EXTRACT INDUCES
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arin-induced suppression of MDR1 ex
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1780 ANTIANDROGENIC AND ANTIPROLIFE
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included in the evaluation, most of
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1799 GUIDANCE ON THE APPLICATION OF
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However, substances with EC3 values
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1816 CD-INDUCED EGFR TRANSACTIVATIO
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1826 KERATIN 7 EXPRESSION IN INDEPE
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centa were collected at the time of
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1845 SYSTEMATIC SCREENING OF YEAST
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underlying the development of co-mo
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eing measured in experimental roden
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ufactured in the US for more than 3
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nine (N7-THB-Gua) and N7-hydroxyphe
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1892 EFFECT OF LAMBDA-CYHALOTHRIN O
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22 in Phase I. Antimicrobial pestic
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kinetic and dynamic differences, an
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iphenyl, saccharin and melamine was
Page 415 and 416:
1930 DEVELOPMENT OF A RELATIVE SOUR
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1939 MODE OF ACTION FOR THE CANCER
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human was about 1.5-fold lower (60
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Disruption of BDEC integrity in alp
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1968 A HUMAN HEPG2 LUCIFERASE ASSAY
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in the offspring during tumor devel
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een developed to investigate perfus
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to 131.73 μg/mL for KLH-specific I
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cell lines (ATCC) were cultured in
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flammation and xenobiotic metabolis
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vide many contributions: with its g
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to-metal joint replacement. For exa
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to be addressed or negotiated. Deci
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especially with anti-TNF therapies.
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genic line Tg(are:eGFP) was created
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2074 COMPUTATIONAL ASSESSMENT OF TH
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2084 INHIBITION OF 11β-HSD1 DECREA
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(T) and express several enzymes inv
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2101 GENISTEIN MODULATION OF BLOOD
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males per group were dosed orally o
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ate the feasibility of assessing re
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changed. Hepatic protein carbonyl l
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sought to examine alterations in he
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2147 A SINGLE AMINO ACID CONTROLS T
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Gstm7) was independent of both CAR
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ility of tungsten trioxide (WO3), t
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ured by real-time PCR array and rel
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glucose, and creatinine levels, and
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Several studies have reported suppr
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exposure between TCDD-exposed labor
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Furthermore, with increasing number
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Society of Toxicology 2010 Author I
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Society of Toxicology 2010 Abstract
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49 th Annual Meeting and ToxExpo A
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The Official Journal of the Society
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