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leading to an overall decrease in respiratory control ratios. Protein levels for Complex IV decreased with age in female APP/PS1 mice. Conversely, APP levels in both male and female APP/PS1 animals were increased as compared to wildtypes. In the organotypic hippocampal slices, basal and maximal oxygen consumption, as well as rates following inhibition with antimycin A could be stably measured over several hours suggesting this methodology could be useful for mitochondrial respiration measurements in tissue, not presently an option using the Clark electrode. Future respiration studies with the extracellular flux analyzer will be applied using the hippocampal slice model in AD transgenic mice. 1616 EFFECT OF AGING ON EXPRESSION OF HEPATIC TRANSPORTERS AND BILE ACID SYNTHESIZING ENZYMES IN MOUSE LIVER. Z. D. Fu, I. L. Csanaky and C. D. Klaassen. Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City, KS. Aging is a process accompanied by increasing macromolecular damage and declining physiological functions in various organs. Most of the studies on age-related gene expression have focused on drug-metabolizing enzymes and only limited to a couple of age groups. Very little information is available on the effect of aging on hepatic transporters. Using multiplex suspension assays, we determined the expression profiles of transporters and bile acid synthesizing enzymes in livers of male and female C57BL/6 mice of 10 age groups, ranging from 3 to 29 months of age. The uptake transporter Oatp1a1 showed the most dramatic decrease with age, starting at 3 months of age. A more gradual decrease with age was observed in other hepatic uptake transporters, starting at about 9 months of age. Most of the efflux transporters had a decrease in expression after one year, such as Mrp2, Mrp6, Bcrp, Bsep, Abcg5 and Abcg8, whereas Mrp4 increased dramatically in female mice with aging. Bile acid synthesizing enzymes Cyp7b1, Cyp8b1, and Cyp27a1 decreased gradually with age; Cyp7a1 decreased only after 15 months, whereas Cyp39a1 increased with age. The majority of the genes studied showed significant gender differences in expression throughout the aging process, including male-predominant Oatp1a1, Bcrp, Cyp7b1 and Cyp8b1, as well as female-predominant Oatp1a4, Oatp2b1, Oct1, Ent1, Ntcp, Mate1, Mdr2, Mrp3, Mrp4, and Cyp39a1. Taken together, these data suggest a potential explanation for altered pharmacokinetics and pharmacodynamics of therapeutic drugs in the elderly, as well as increased cholesterol levels due to decreased conversion of cholesterol to bile acids. Understanding the effects of aging on drug processing genes may provide useful information in determining the effective and safe dosage of drugs for the elderly. (Supported by NIH grants ES009649, ES013714, ES009716, ES007079, and RR021940) 1617 HEPATOCYTE-SPECIFIC DELETION OF NADPH- CYTOCHROME P450 REDUCTASE (H-CPR-NULL) IN MICE DISTURBS BILE-ACID HOMEOSTASIS BY MINIMIZING THE CLASSICAL PATHWAY OF BILE- ACID BIOSYNTHESIS. X. Cheng, Y. Zhang and C. D. Klaassen. Pharmacology, Toxicology, and Therapeutics, KUMC, Kansas City, KS. Cyp7a1 and 8b1, two critical enzymes for the classic microsomal route of bile-acid (BA) biosynthesis, requires Cpr for their activities. The alternative BA biosynthesis pathway is initiated by mitochondrial Cyp27a1, and the rate-limiting step in this pathway is cholesterol delivery to mitochondrial inner membrane by StAR. To investigate the importance of the classical BA biosynthesis pathway, total and individual BAs, as well as expression of BA biosynthetic enzymes and transporters were characterized in H-Cpr-null mice. Total serum BA concentrations were 2-fold higher in H-Cpr-null than wild-type mice and consisted of increases in taurineconjugated secondary bile acids DCA (10-fold) and UDCA (3-fold). The higher serum concentration of BAs was not due to changes of BA uptake (Ntcp) or efflux (Bsep) transporter, but apparently due to increases in basolateral efflux transporters Mrp3 (40%) and Mrp4 (100%) in liver, as well as increases of apical BA uptake Asbt (38%) and basolateral efflux Ostα/β (150%) transporters in intestine. BA concentrations in livers of H-Cpr-null mice decreased 60%, but the total amount of bile acids per liver only decreased 26%, due to a 50% increase in liver size. The liver concentration of CA, which is thought to be synthesized only by the classical pathway, decreased 86% in H-Cpr-null mice. Compared to wild-type mice, H- Cpr-null mice had higher mRNA expression of StAR (90%) and Cyp27a1 (30%), both of which are essential for the alternative BA biosynthetic route. The mRNA of two proteins that decrease BA biosynthesis, namely Shp in liver and Fgf15 in intestine, were decreased 50 and 90%, respectively, in the H-Cpr-null mice. In conclusion, marked changes in BA biosynthesis, composition, and transporters occur in H-Cpr-null mice in an apparent attempt to maintain overall bile-acid homeostasis via enhancing the alternative BA biosynthesis pathway. (Supported by NIH grants ES009649, ES009716, ES013714, and RR021940) 1618 LIVER BILE ACID METABOLISM IN MALE AND FEMALE C57BL/6 MICE FED BILE ACID- SUPPLEMENTED DIETS. Y. Zhang and C. D. Klaassen. Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS. An improved UPLC-MS/MS method was established for the simultaneous analysis of bile acids and keto bile acids, as well as their glycine, taurine, sulfate, and glucuronidate conjugates in mouse livers. This simple and sentitive method was validated and applied to investigate liver bile acid metabolism in both male and female C57BL/6 mice fed various diets supplemented with 1% cholic acid (CA), 0.3% deoxycholic acid (DCA), 0.3% chenodeoxycholic acid (CDCA), 0.3% lithocholic acid (LCA), 3% ursodeoxycholic acid (UDCA), or 2% cholestyramine (resin). Results from these studies indicate that bile acids were biotransformed by the intestinal bacteria before they entered the liver, where the majority of them were conjugated with taurine. The bile acid profiles in mouse liver were similar between CA and DCA feeding, as well as between CDCA and LCA feeding. CA feeding suppressed both the classic and alternative pathways of liver bile acid biosynthesis, whereas CDCA feeding mainly suppressed the classic pathway. Gender differences of liver bile acid composition were observed after CA, DCA, CDCA, and LCA feedings, but were not prominent after UDCA feeding. Sulfation of CA or CDCA was at the 7-OH position, and was increased by CA or CDCA feeding in male mouse livers more than in females. In contrast, sulfation of LCA and taurolithocholic acid (TLCA) at the 3-OH position was female predominant, and increased by UDCA and LCA feedings. In addition, feeding the resin also increased sulfation of CA and CDCA. Glucuronidation of bile acids was a minor bile acid metabolic pathway in mice, which was detected only after UDCA feeding. In summary, the present systematic study on liver bile acid metabolism will aid in interpreting bile acid-mediated gene regulation, as well as hepatotoxicity and therapeutic use of various bile acids. (Supported by NIH ES009716, ES013714, ES009649, RR021940) 1619 BILE ACIDS INCREASE PROINFLAMMATORY GENE EXPRESSION IN HEPATOCYTES BY EARLY GROWTH RESPONSE FACTOR-1-DEPENDENT AND INDEPENDENT MECHANISMS. K. Allen 1 , N. Kim 1, 2 and B. L. Copple 1 . 1 Pharmacology, Toxicology, and Experimental Therapeutics, University of Kansas Medical Center, Kansas City, KS and 2 Pharmacy, Pusan National University, Busan, Republic of Korea. Cholestasis occurs when excretion of bile acids from the liver is interrupted causing liver injury in both humans and animals. Recent studies have shown that inflammation exacerbates injury during cholestasis. However, the molecular mechanism by which cholestasis drives inflammation in the liver is not known. Data from our laboratory has shown that early growth response factor-1 (Egr-1) may regulate inflammation thru upregulation of the proinflammatory mediators intercellular adhesion molecule-1 (ICAM-1) and macrophage inflammatory protein-2 (MIP-2) during cholestasis. Also, deoxycholic acid is able to induce Egr-1 expression in isolated hepatocytes. However, whether proinflammatory mediators increase in hepatocytes in response to bile acid exposure, and if this occurs by Egr-1-dependent mechanisms is unknown. Accordingly, the hypothesis was tested that bile acids increase expression of inflammatory mediators in hepatocytes by Egr-1-dependent mechanisms. For these studies, hepatocytes were isolated from wild-type and Egr-1 knockout mice, and exposed to DCA, chenodeoxycholic acid (CDCA), and taurocholic acid (TCA). Bile acids increased levels of several proinflammatory mediators, including cytokines (IL-1β, IL-6, IL-10), chemokines (MIP-2, KC, IP-10, I-TAC, MCP-1, RANTES, MCP-3, MIP-1α, MIP-2α, MIP-3α, LIX, SR-PSOX, MCP-3, BCL, SR-PSOX), adhesion molecules (ICAM-1, VCAM-1), enzymes in arachidonic acid metabolism (COX-2), and other proteins that influence immune cell levels and function (PAI-1, uPAR, G-CSF, GM-CSF). Upregulation of several of these genes was reduced in hepatocytes isolated from Egr-1 knockout mice including ICAM-1 and MIP-2. These data demonstrate that bile acids increase proinflammatory gene expression in hepatocytes by Egr-1-dependent and independent mechanisms. 1620 THROMBIN SIGNALING ENHANCES TGF-BETA INDUCTION OF INTEGRIN BETA6 IN BILE DUCT EPITHELIAL CELLS. B. P. Sullivan and J. P. Luyendyk. Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS. Damage to intrahepatic bile ducts causes cholestasis, inflammation, coagulation cascade activation and liver fibrosis. Recent studies have shown that the αVβ6 integrin, which activates the fibrogenic cytokine TGF-β, contributes to liver fibrosis. 344 SOT 2010 ANNUAL MEETING
Expression of the β6 integrin (Itgβ6) is restricted to bile duct epithelial cells (BDECs) in the liver after common bile duct ligation. However, the mechanisms of Itgβ6 mRNA regulation in BDECs have not been identified. We tested the hypothesis that coagulation protease signaling induces Itgβ6 mRNA expression in BDECs. Treatment of transformed human BDECs (MMNK-1) with thrombin or protease activated receptor-1 (PAR-1) agonist peptides (TFLLRN or SFLLRN) induced the expression of interleukin 8 (IL-8), a chemokine induced by PAR-1 signaling. However, neither thrombin nor agonist peptides increased Itgβ6 mRNA levels in MMNK-1 cells. In contrast, treatment of the MMNK-1 cells with TGF-β increased Itgβ6 mRNA levels without affecting IL-8 expression. As thrombin and TGF-β are likely generated concurrently during cholestatic liver injury, we determined whether thrombin enhanced TGF-β induction of Itgβ6 mRNA. Co-treatment with either thrombin or the agonist peptides significantly enhanced TGF-β induction of Itgβ6 mRNA, whereas co-treatment with a scrambled peptide (FS- LLRN) was without effect. Thrombin, but not TGF-β, activated the p38 and JNK1/2 MAPK signaling pathways. Itgβ6 mRNA induction in cells co-treated with thrombin and TGF-β was significantly reduced by a p38 inhibitor (SB203580) and a JNK1/2 inhibitor (SP600125). Taken together, the results suggest that thrombin activation of p38 and JNK1/2 signaling enhances TGF-β dependent induction of the Itgβ6. Further elucidation of the mechanisms whereby these fibrogenic mediators synergistically induce the Itgβ6 and contribute to fibrogenesis may reveal novel strategies for the treatment of cholestatic liver disease. 1621 ONTOGENY OF HEPATIC EFFLUX TRANSPORTERS IN OBESE MICE. A. C. Donepudi, Q. Cheng and A. Slitt. Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, RI. ATP binding cassette (Abc) transporters are a family of efflux transporters in liver important for the excretion of xenobiotics. Ob/ob mice are a congenic mouse strain that have a spontaneous mutation in gene that encodes leptin. Phenotypical changes in ob/ob mice are observed at week 4, with marked Abc transporter expression changes in liver by week 11, as compared to lean control mice (C57BL/6). The ontogeny of Abc transporter expression in ob/ob mice has not been described, but may point to factors responsible for inducing transporter expression in obesity. The purpose of this study is to correlate changes in liver Abc transporter expression with phenotype changes and liver pathology in ob/ob and lean mice. Ob heterozygous mice were bred and their progeny were genotyped to confirm leptin mutation and gender. Livers from male and female lean and ob/ob homozygous mice littermates at 1, 3, 4 and 8 weeks of age were collected and mRNA was quantified. Expression of Abcc3 and 4 in males and females ob/ob mice increased with age. Abcc5 expression in both males and females decreased with age, whereas Abcc6 and Abcb1a expression decreased with age in only males ob/ob mice. At week 1, Abcc3 and 4 mRNA expression was downregulated in ob/ob compared to leans, whereas this observation was reversed at 3, 4 and 8 weeks of age. Abcg2 expression in ob/ob males was same as in leans at week 1, but its expression was upregulated in both male and female mice at 3, 4 and 8 weeks as compared to lean mice. Abcc2 expression in lean mice remained fairly constant in all age groups but increased in ob/ob mice with age. In conclusion, ontogeny of hepatic efflux transporters in ob/ob mice is different from lean mice, with week 3 and 4 being the time points where changes in the expression pattern were observed. Thus far, our data indicates that week 3 and 4 are pivotal time points for the upregulation of Abc transporters during obesity and indicate that leptin signaling along with physiological changes associated with the onset of obesity are important factors for regulation of transporter expression in liver. 1622 LONG-TERM EFFECT OF A HIGH CHOLESTEROL DIET ON HEPATIC DRUG TRANSPORTER EXPRESSION IN AKR AND C57BL/6 MICE. M. A. Paranjpe and A. Slitt. Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, RI. Obesity is a major concern in the United States, with its major cause being consumption of a diet rich in fat and cholesterol (CH). High CH levels are known to cause liver and gallbladder disease. Common amongst them is cholelithiasis, which may further lead to gallbladder cancer and cholestasis. The purpose of this study was to determine the long-term effect of feeding lithogenic diet on drug transporter expression in 2 strains of mice which differ in their susceptibility towards CH crystal formation in gallbladder bile. Studies have shown that AKR mice are resistant, whereas C57Bl/6 mice are susceptible to CH gallstone formation. Adult male AKR and C57Bl/6 mice were fed with lithogenic (15% fat, 1.25% CH, 0.5% sodium cholate) or standard diet (5% fat) for 8 wks, then gallbladders, livers and blood were collected. The lithogenic diet resulted in increased crystal formation in the gallbladder biles of C57Bl/6 mice as compared to AKR. Serum CH levels increased with the lithogenic diet in both the strains of mice but no strain difference was observed. The total RNA was isolated from liver and the mRNA expression of transporters like multidrug resistance-associated proteins (Mrps) and organic anion transporting polypeptides (Oatps) was determined using Quantigene 2.0 plex assay. The lithogenic diet increased Oatp1a4, and 1b2 mRNA levels in livers of AKR mice and decreased Oatp1a4 levels in livers of C57Bl/6 mice. The lithogenic diet increased Mrp1 in both the strains. Mrp2, 3 and 4 mRNA expression was upregulated in livers of the AKR mice, but Mrp 3 and 4 were downregulated in livers of the C57Bl/6 mice. Nuclear factor E2 related factor 2 (Nrf2) is a transcription factor that regulates the expression of many enzymes and transporters in liver that mediate metabolism and transport processes. The lithogenic diet significantly induced the Nrf2 mRNA expression in AKR mice but not in the C57Bl/6 mice, which could suggest the possibility of Nrf2 playing a role towards the resistance of gallstone susceptibility. (NIH KES013782A, 5R01ES016042-02) 1623 CHANGES IN EXPRESSION OF LIVER MRP2 EXPRESSION IN MOUSE MODELS OF FASTING AND CALORIC RESTRICTION. S. Kulkarni and A. Slitt. Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, RI. Epidemiological and clinical studies show that obesity changes disposition of various drugs. Mouse models of obesity demonstrate altered drug metabolizing enzyme and drug transporter expression. Multidrug resistance-associated protein 2 (Mrp2) is a biliary efflux transporter important in transport of glucuronide conjugates of various drugs and endogenous as well as environmental compounds. Altered expression of Mrp2 changes disposition of acetaminophen, morphine and thyroid hormone conjugates in rodent models of disposition. CDC estimates that two thirds of American population is undergoing caloric restriction (CR) / fasting to combat obesity. Thus, it is important to study dispositional and transcriptional circuitry changes in both obese and lean individuals undergoing nutrient deprivation. The purpose of this study was to understand changes in (1) expression of Mrp2 and (2) binding of transcription factors (TF) important in xenobiotic metabolism as a function of fasting or CR in C57Bl/6 (lean) and ob/ob (obese/OB) mouse models. Lean and ob/ob mice were fasted for 30 hours or put on a 40% reduced caloric diet for a period of 10 weeks. Fasting did not affect mRNA or protein expression of Mrp2 in livers of either mouse model. CR increased Mrp2 mRNA expression by about 1.2 and 2 folds in lean and OB CR mice over fed controls, respectively. Changes in TFs binding to their consensus response elements (RE) were analyzed using liver nuclear extracts from the CR mice. Obesity increased AhR, NFκβ, Nrf2, CREB, and PPAR binding by 147-275 percent to their respective RE as compared to lean fed controls. This increased binding in hepatic nuclear fractions from OB mice was reversed by CR. In summary, our data indicate that CR can restore Mrp2 expression in liver to that detected in livers of lean mice, and this is associated with changes in several TFs. Overall, these data indicate that there is potential to restore hepatic disposition changes associated with obesity through caloric restriction. (KES013782A, RES016042A) 1624 TRANSPORTER EXPRESSION IN DB/DB AND DIET- INDUCED OBESE (DIO) MICE. V. R. More and A. L. Slitt. Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, RI. Diabetics are found to have altered pharmacokinetic and toxicological profiles for certain drugs. As transporters play important role in drug disposition, it is important to characterize transporter expression in diabetes. In the present study, transporter expression (mRNA and protein) in livers and kidneys of adult male and female db/db mice, as well as male diet-induced obese (DIO) mice was determined. Db/db mice, which have a spontaneous mutation in the leptin receptor, show increased body weight, severe hyperglycemia and hyperinsulinemia. DIO mice are fed high fat diet (60% fat) from six weeks of age; they have slightly increased body weight, mild hyperglycemia and hyperinsulinemia. Expression of uptake transporters was decreased in livers and kidneys of db/db mice, including organic anion transporting polypeptide (Oatp) 1a1, 1a4 and organic anion transporter 2. Oatp1a1 mRNA expression was almost non-detectable in livers and kidneys of db/db male mice compared to wild type. In general, expression of multidrug resistance-associated protein (Mrp) efflux transporters was significantly increased in livers of db/db mice. Specifically, Mrp3 and 4 mRNA and protein levels increased greater than 2 fold in db/db male mice livers as compared to wild type mice. Mrp3 mRNA expression was markedly down regulated in kidneys of male db/db mice as compared to wild type. Similarly, in the livers of DIO mice, Mrp3 and 4 mRNA expressions were increased 3.3 and 1.4 fold as compared to that in controls. In DIO mice, uptake transporter expression in liver and kidney, as well as kidney Mrp expression remained unchanged. In summary, expression of numerous transporters SOT 2010 ANNUAL MEETING 345
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The Toxicologist Supplement to Toxi
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The Toxicologist Supplement to Toxi
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1 BIOLOGICAL PATHWAY ANALYSIS: AN I
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11 ICH INITIATIVES FOR CONDUCTING P
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models. Experimental approaches and
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30 SILICA AND ASBESTOS IMMUNOTOXICI
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40 NONCANCER TOXICITY POTENTIAL AT
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ased products for patient administr
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nase regulates Hsp27-induced reorga
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exposure resulted in splenomegaly.
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We investigated the effect of imati
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well plate prevented free cell move
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98 DERIVING SIGNATURES OF IN VIVO T
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sulfate, cinnamic aldehyde, 2,4-din
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The final product will be a system
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mercially available STP brands by m
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for six weeks, with 10 mg/kg azoxym
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eceived RES post-TCDD exposure when
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morigenesis. Knocking down of JARID
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163 MICROPET IMAGING OF [18F]-DFNSH
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These results are comparable to tha
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activity as assessed by lever press
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for measured physico-chemical param
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199 DEVELOPMENT OF A MULTIPARAMETER
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To cause PLD, a drug needs to enter
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In contrast to the parent PBDEs and
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transiently transfected HEK 293 cel
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TCDD exposure, 24 h prior to a 20 %
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244 NON-ADDITIVE EFFECTS OF PCB153
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253 COMPARISON OF MIXTURE TOXICITY
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two cerium oxide nanoparticles of v
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271 SIZE-DEPENDENT EFFECTS OF TUNGS
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adigms such as Tox 21 and Toxcast,
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QDs with emission maximum at 800nm
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Cleveland, while others were found
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without the need of animal testing.
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Conclusions: These results are cons
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ing oxime reactivation and organoph
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335 A NON-OXIME IMPROVES SURVIVAL I
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alties suffer from permanent lung i
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ies have established inflammatory b
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363 GENETIC VARIATION IN ISOGENIC M
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372 EVALUATING THE BIOLOGICAL INTER
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dose of 1/20 LD50 (400 mg/kg.bwt) f
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median CR-adjusted isoflavone conce
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data indicate that AhR deletion pro
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February 2006). The rabbit is one o
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tal neurotoxicity (DNT) test (OECD
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of selected microorganisms that are
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BVI. Histopathological analysis was
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446 MOLECULAR CLONING AND CHARACTER
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portant in predicting risk. CYPs 1A
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ats, which involves metabolic activ
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473 BOVINE CORNEAL OPACITY AND PERM
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482 TYPE III DEIODINASE (D3) IS PRO
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tancy evaluation and ranking of bat
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501 CHARACTERIZATION OF ESTERASE, G
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510 REDOX CYCLING BY ENDOGENOUS 2-
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prostate cancer cells. All 8 BEL de
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metallic nickel nanoparticles. Acti
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variety of more or less reactive ch
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550 QUALIFICATION STRATEGIES-GENOTO
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ferentiation, and 3) how mixtures o
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572 LOW-CHRONIC ARSENIC EXPOSURE: E
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582 IDENTIFICATION OF SENSITIVE URI
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duced by the genetic outcross of fe
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fects of new compounds are equally
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acterize the current state of the s
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620 CHARACTERIZATION OF POTENTIAL I
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ways. Moreover, both MAP kinase and
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641 POPS IN THE U.S. POPULATION AND
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studies such as the NCS, consider h
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the beginning of the academic caree
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trophil infiltration, a significant
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tactic response and optokinetic res
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usually high spontaneous PIG-A MFs.
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699 PROMUTAGEN ACTIVATION AND P450
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oxodG in bone marrow, spleen, kidne
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718 GENOTOXICITY OF ORGANIC EXTRACT
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ment were 18.0 and 4.5 nM for BEAS-
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strongest activation of nuclear fac
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746 MACROPHAGE INHIBITORY CYTOKINE-
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screening of cell migration. High-c
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dase inhibition). In contrast, inhi
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mice; the decrease was more pronoun
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Markers of oxidative damage reached
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793 PULMONARY RESPONSE, OXIDATIVE S
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cilitate clinical and industrial ap
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sion of p-p38, p-p53, p21 and cycli
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821 KIDNEY INJURY MOLECULE-2 GENE D
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commercial applications, and have b
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developmental effects. The residual
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strand breaks in an in vitro model
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etate (immunotoxicity). 2,4-D was t
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867 MELATONIN AMELIORATES CYCLOPHOS
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pharmacokinetic (PBPK) models. Ten
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of radiolabeled Mn (carrier-free 54
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893 UNVEILING ASSOCIATIONS BETWEEN
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using area under the concentration
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912 COMMERCIAL FISH DIETS INDUCE VI
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922 A STUDY OF PHOTOTOXICITY FOLLOW
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from 0.1 to 2.9 g/L (saturated vapo
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vasive method for assessing several
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950 ARSENITE DOWN-REGULATES THE CAR
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inflammatory signaling is altered b
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treated wood. Seventy-five of 132 w
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ergy homeostasis and raising levels
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treated with mercury and then with
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997 IN VIVO CORRELATES OF THE MANGA
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of the panel. The panel was compris
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sponse, location, and severity scor
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tant source of n-3 fatty acids such
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old for serious, irreversible or es
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1045 SUBCHRONIC TOXICITY EVALUATION
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sites collected 3 days after inject
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1063 MOLECULAR MECHANISM OF OLANZAP
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esponses, and can be available for
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hence more physiologically relevant
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thesized apoproteins, so we tested
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vate CYP3A5 but could be released b
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1108 STYRENE-INDUCED TOXIC EFFECTS
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1118 THE PRESENCE OF DIETHYL FUMARA
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zebrafish cells were first exposed
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utene-1,4-dial, which has been show
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groups, largely due to lower non-HD
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Exposure to gluten in individuals w
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contrast to VGSC activators such as
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1175 70% HYDROFLUORIC ACID (HF) CUT
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axis. An increase in hyaline drople
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1194 esiRNA AND siRNA HIGH-THROUGHP
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1203 ARYL HYDROCARBON RECEPTOR-DNA
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permeability (calcein), mitochondri
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olytic caspase activation, caspase-
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teristics of a human T-type voltage
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80% of the activity from the yellow
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1251 DEVELOPMENTAL EXPOSURE TO DELT
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1260 MANEB ENHANCES MPP + -INDUCED
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demonstrated by knockdown of beclin
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1278 PINK1 AND MITOCHONDRIAL DYNAMI
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treatment for number of live worms.
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1297 INVESTIGATION OF THE NEUROTOXI
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1306 DEVELOPMENT OF AN IN VITRO ASS
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1315 EVALUATION OF 3- AND 1-METHYLH
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prior to kainic acid-induced seizur
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1334 AFFECT OF GENETIC VARIATION ON
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1346 THE OTHER WORLD OF THE TRANSCR
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strate, leading to excess microvesi
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1368 OVERVIEW OF THERAPEUTIC VACCIN
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Page 351 and 352: ats (10 μg/kg TCDD). Here we repor
Page 353 and 354: at liver slices and how the metabon
Page 355 and 356: with gender differences in AUC and
Page 357 and 358: oxetine (30 mg/kg reduced to 15 mg/
Page 359 and 360: eleased from necrotic cells where i
Page 361 and 362: plants, they are present in surface
Page 363 and 364: ferentiation (quantitative in-cell
Page 365 and 366: control for macrophage activation).
Page 367 and 368: to 0.5μg/ml. Minimal inhibitory co
Page 369 and 370: lines tested. Given that dex and AT
Page 371 and 372: tion in the absence of an immune re
Page 373 and 374: treated rats had lower calcium load
Page 375 and 376: 1740 PROFILING COMPOUNDS WITH CARDI
Page 377 and 378: dothelial cells confirmed caveolin-
Page 379 and 380: 1758 GINKGO BILOBA EXTRACT INDUCES
Page 381 and 382: arin-induced suppression of MDR1 ex
Page 383 and 384: 1780 ANTIANDROGENIC AND ANTIPROLIFE
Page 385 and 386: included in the evaluation, most of
Page 387 and 388: 1799 GUIDANCE ON THE APPLICATION OF
Page 389 and 390: However, substances with EC3 values
Page 391 and 392: 1816 CD-INDUCED EGFR TRANSACTIVATIO
Page 393 and 394: 1826 KERATIN 7 EXPRESSION IN INDEPE
Page 395 and 396: centa were collected at the time of
Page 397 and 398: 1845 SYSTEMATIC SCREENING OF YEAST
Page 399 and 400:
underlying the development of co-mo
Page 401 and 402:
eing measured in experimental roden
Page 403 and 404:
ufactured in the US for more than 3
Page 405 and 406:
nine (N7-THB-Gua) and N7-hydroxyphe
Page 407 and 408:
1892 EFFECT OF LAMBDA-CYHALOTHRIN O
Page 409 and 410:
22 in Phase I. Antimicrobial pestic
Page 411 and 412:
kinetic and dynamic differences, an
Page 413 and 414:
iphenyl, saccharin and melamine was
Page 415 and 416:
1930 DEVELOPMENT OF A RELATIVE SOUR
Page 417 and 418:
1939 MODE OF ACTION FOR THE CANCER
Page 419 and 420:
human was about 1.5-fold lower (60
Page 421 and 422:
Disruption of BDEC integrity in alp
Page 423 and 424:
1968 A HUMAN HEPG2 LUCIFERASE ASSAY
Page 425 and 426:
in the offspring during tumor devel
Page 427 and 428:
een developed to investigate perfus
Page 429 and 430:
to 131.73 μg/mL for KLH-specific I
Page 431 and 432:
cell lines (ATCC) were cultured in
Page 433 and 434:
flammation and xenobiotic metabolis
Page 435 and 436:
vide many contributions: with its g
Page 437 and 438:
to-metal joint replacement. For exa
Page 439 and 440:
to be addressed or negotiated. Deci
Page 441 and 442:
especially with anti-TNF therapies.
Page 443 and 444:
genic line Tg(are:eGFP) was created
Page 445 and 446:
2074 COMPUTATIONAL ASSESSMENT OF TH
Page 447 and 448:
2084 INHIBITION OF 11β-HSD1 DECREA
Page 449 and 450:
(T) and express several enzymes inv
Page 451 and 452:
2101 GENISTEIN MODULATION OF BLOOD
Page 453 and 454:
males per group were dosed orally o
Page 455 and 456:
ate the feasibility of assessing re
Page 457 and 458:
changed. Hepatic protein carbonyl l
Page 459 and 460:
sought to examine alterations in he
Page 461 and 462:
2147 A SINGLE AMINO ACID CONTROLS T
Page 463 and 464:
Gstm7) was independent of both CAR
Page 465 and 466:
ility of tungsten trioxide (WO3), t
Page 467 and 468:
ured by real-time PCR array and rel
Page 469 and 470:
glucose, and creatinine levels, and
Page 471 and 472:
Several studies have reported suppr
Page 473 and 474:
exposure between TCDD-exposed labor
Page 475 and 476:
Furthermore, with increasing number
Page 477 and 478:
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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