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suggest that TRX possesses novel immunomodulatory properties as a result of its ability to modulate IL-1β production and/or signalling. In contrast, LF inhibits the activity of TNF-α. The bioactivity of these molecules following simple topical application demonstrates that these proteins can access the viable epidermis and may represent an opportunity for the development of novel anti-inflammatory reagents. 96 PROTEIN ALLERGENICITY AND DIGESTIBILITY: COMPARISONS OF PEPSIN AND CATHEPSIN. E. Foster, I. Kimber and R. J. Dearman. University of Manchester, Manchester, United Kingdom. An association between protein allergenicity and resistance to pepsin digestion has been reported previously, however, such is not complete with examples of labile allergens and resistant non-allergens observed. Given the central role of antigen presenting cells, such as dendritic cells (DC), in the development of immune and allergic responses, the stability of allergens to intracellular processing may be more relevant than resistance to pepsin digestion. We have characterised the expression by DC of cathepsins (proteolytic enzymes), and compared the proteolytic activity of the most highly expressed cathepsin with pepsin. Cathepsin expression in bone marrow-derived DC (BMDC) and in mesenteric lymph node DC derived from BALB/c strain mice was characterised by flow cytometry. BMDC expressed detectable levels of cathepsin D, E and S, with cathepsin D being the most highly expressed, with a similar pattern observed in DC isolated from mesenteric lymph nodes. Digestion studies revealed that the allergens β-lactoglobulin (BLG), hen egg lysozme (HEL) and ovalbumin (OVA) were relatively resistant to pepsin, although bovine serum albumin (BSA) was labile, as were the non-allergens hemoglobin (HB) and horseradish peroxidise (HRP). In contrast, all 4 allergens were stable to overnight digestion with cathepsin D, although fragments were observed for BSA. HB was labile to cathepsin D whereas fragments were recorded for HRP. As intracellular digestion occurs under reducing conditions, the impact of prior chemical reduction was explored. Reduced BLG and OVA were labile to pepsin and fragments were observed following cathepsin D digestion. Generally, allergens were more stable than non-allergens to digestion by both enzymes and chemical reduction increased lability. Although a wider range of allergens and non-allergens needs to be examined, these data suggest that allergenicity correlates more strongly with resistance to digestion by cathepsin D than with pepsin. 97 INHALATION OF ORTHO-PHTHALALDEHYDE VAPOR CAUSES SYSTEMIC SENSITIZATION AND ALLERGIC INFLAMMATION IN THE LYMPH NODES, NASAL MUCOSA, AND LUNG OF MICE. V. J. Johnson, W. Wang, K. Fluharty, B. Yucesoy and J. S. Reynolds. CDC/NIOSH, Morgantown, WV. Ortho-Phthalaldehyde(OPA) is increasingly being substituted for glutaraldehyde as a high-level disinfectant for sensitive medical devices. However, toxicological data on OPA safety is lacking. Safety concerns for glutaraldehyde include acute nasal toxicity and sensory irritation as well as sensitization leading to occupational rhinitis and asthma. Since OPA is a dialdehyde like glutaraldehyde and functions as a disinfectant due to its high reactivity for biological macromolecules, it is reasonable to expect similar respiratory hazards. Several case reports have been published supporting this hypothesis showing development of respiratory hypersensitivity reactions in healthcare workers and patients exposed to OPA. The purpose of this study was to determine if OPA is a respiratory sensitizer using a murine model. Mice were exposed via inhalation to OPA vapor 4 hrs/day for 3 days; rested for 11 days; challenged with OPA vapor 4 hrs/day for 3 days and then sacrificed 24 hrs after the final exposure. Lungs, nasal mucosa, head-draining lymph nodes (LN) and serum were collected and processed for cytokine gene expression and flow cytometry. OPA-specific antibodies were detected in the serum of exposed mice. OPA inhalation induced a dose dependent increase in LN IL-4 expression and B-cell proliferation. Importantly, there was a concomitant increase in IgE+ B-cells. Strong Th2 cytokine expression in the nasal mucosa increased with OPA dose whereas the inverse was observed for IFNγ expression, a cytokine expression pattern commonly observed in response to respiratory allergens. Th2 cytokine expression was also increased in the lung although to a lesser extent. These data demonstrate that OPA inhalation induces a predominant Th2 cytokine response in the respiratory tract and draining LN. Importantly, OPA inhalation induced isotype switching to IgE in the draining LN supporting the development of an allergic immune response. Overall, this study suggests that inhalation of OPA vapor in mice can induce respiratory allergy. 20 SOT 2011 ANNUAL MEETING 98 CONTACT SENSITIZING POTENTIAL OF HEPTACHLOR IN FEMALE BALB/C MICE. R. P. Frawley 1 , W. Auttachoat 2 , M. J. Smith 2 , R. D. Brown 2 , T. L. Guo 2 , K. L. White Jr 2 and D. R. Germolec 1 . 1 National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC and 2 Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA. Heptachlor (HPT) is a chlorinated cyclodiene insecticide that was used extensively in the 1950’s through 1980’s in agriculture, and in commercial and domestic buildings. Banned by the Environmental Protection Agency (EPA) for most uses (except for fire ant control in underground power cable boxes) since 1988, low levels of HPT residues persist in the environment. Human exposure can occur through contact with contaminated soil or building materials; consumption of contaminated meat, fish or dairy products; or production and application of HPT insecticides. The objective of this study was to evaluate the sensitization potential of HPT in female BALB/c mice following dermal exposure using the ICCVAM-validated local lymph node assay (LLNA) in combination with a measurement of irritancy, and the mouse ear swelling test (MEST). Sensitization was evaluated at concentrations that did not induce overt toxicity. HPT was applied to the dorsa of both ears daily for three days. There was no increase in ear swelling 24 hr following the third application at 0.2%-5.0%, indicating that HPT is not an irritant. Cervical (auricular) lymph node cell proliferation was statistically increased (72 hr post-application) at 2% HPT relative to the vehicle control, however, the increase did not reach a sensitization index (SI) of 3. In the MEST, mice sensitized with 1% and 2% HPT and challenged with 2% HPT exhibited significant increases in percent ear swelling, compared to the vehicle irritancy control, at 24 hr, but not at 48 hr, post-challenge. In summary, based on lack of irritancy and on statistical significance in the LLNA and MEST, HPT can be characterized as a sensitizer, but not an irritant. 99 HUMAN LINE1 PROMOTER ACTIVITY IS ENHANCED BY CHEMICAL AND DRUG-INDUCED STRESS IN HEPG2 CELLS. N. Terasaki, M. Kajikawa and N. Okada. Department of Biological Science, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, Japan. Sponsor: J. Sugimoto. Long interspersed element 1 (LINE1), which is one of retrotransposons, constitutes 17 % of the human genome. 80-100 human LINE1 elements are currently active and can mobilize into a new location of the genome, resulting in alteration of the genomic information. Therefore, active LINE1 elements are considered as a sort of endogenous mutagens. In previous studies, some stresses, for example, heat shock, gamma radiation, UV irradiation and some agents are reported to induce mobilization of retroposons. In this study, to investigate widely what chemicals and drugs have the potential to enhance the LINE1 promoter activity, we established a reporter gene assay system in HepG2 cells using human LINE1. We cloned the 5’- UTR of L1.3, which is one of the most active human LINE1s, in the upstream of a luciferase gene and used it in the assay. The LINE1 promoter activity was measured at 6 and 24 hours after exposure to compounds. We assessed 106 compounds which include anticarcinogenic agents, nonsteroidal antiinflammatory drugs (NSAIDs), hypolipidemic agents, statins and some compounds that induce ER stress, oxidative stress, mitochondrial dysfunction etc. More than 1.5-fold increase of the LINE1 promoter activity was observed by the treatment of 9 compounds (merbarone, benzo(a)pyrene, exo1, iodoacetamide, citrinin, cyclosporine A, fenofibrate, bezafibrate, diflunisal and salicylamide) at both 6- and 24-hour points. Other 12 compounds also elevated the LINE1 promoter activity by 1.2- to 1.5-fold. These results suggest that various toxicants and drug stresses might have the potential to cause genomic mutations in a human body by inducing LINE1 mobilization. Therefore, we should keep in mind the possibility of activation of retrotransposons during drug discovery processes. 100 IN UTERO BISPHENOL A EXPOSURE ALTERS METASTABLE EPIALLELE AND GLOBAL DNA METHYLATION PATTERNS IN MOUSE OFFSPRING. M. S. Nahar, C. Weinhouse, O. S. Anderson, T. R. Jones, S. A. Liberman, L. S. Rozek and D. C. Dolinoy. Environmental Health Science, University of Michigan, Ann Arbor, MI. Genetically identical individuals such as monozygotic twins and inbred mice often display phenotypic discordance, even after controlling for environment. Therefore, epigenetic plasticity has been proposed to play a role in the diverse phenotypes of individuals. Metastable epialleles variably express loci in genetically identical individuals due to epigenetic marks established early in development. Strikingly, these
alleles are especially vulnerable to environmental exposures. The murine viable yellow agouti (A vy ) locus is a well-established metastable epiallele that serves as an epigenetic biosensor. Using this model, we previously reported that maternal exposure to bisphenol A (BPA), the monomer forming polycarbonate plastic and epoxy resins, decreases DNA methylation at the A vy locus. Herein, we assess global DNA methylation levels as well as novel murine metastable epiallele methylation patterns in order to identify additional epigenetic loci sensitive to maternal BPA exposure. DNA from d22 liver was isolated from A vy /a and a/a mice exposed in utero and during lactation to 50 mg BPA/kg diet (N=90) or a control diet (N=76). Global methylation levels were assessed via the Luminometric Methylation Assay, and DNA methylation at candidate metastable epialleles Dnajb1 and Glcci1 was analyzed via bisulfite sequencing. Global DNA methylation levels were significantly higher in BPA-exposed mice compared to controls (70.4% and 66.4%, respectively; p-value=0.001). Mean Glcci1 methylation levels at two intracisternal A particle (IAP) repeats were higher in BPA exposed mice (95.2% and 91.3%) compared to controls (93.7% and 89.9%; p-value= 0.001). No exposure differences were observed in the promoter of Dnajb1, which exhibited low levels of methylation in both groups. Both global and site-specific methylation changes may be useful toxicological tools as epigenetic biosensors of environmental exposure and aid in evaluating disease susceptibility. 101 IDENTIFICATION OF CANCER SPECIFIC METHYLATED PROMOTER REGION IN MOUSE BONE MARROW ORIGINATED TUMOR CELLS. H. Shin 1 , S. Jeong 2 , J. Kang 1 , Y. Park 1 , S. Son 1 and H. Kang 1 . 1 Toxicology & Chemistry Division, NVRQS, Anyang, Republic of Korea and 2 GLP Research Center, College of Natural Sciences, Hoseo University, Asan City, Republic of Korea. DNA methylation has profound roles in gene regulation and is known as contributing factors in disease and cancer. In cancer cells, abnormal methylation of CpG islands has been widely described. The etiology of bone marrow originated cancer is still largely unknown, but exposure to chemicals has been suggested to be cancer risk factors and associated with the pathologies. The aim of this study is to identify commonly altered methylation genes in mouse bone marrow originated cancer cells compared to normal bone marrow cell for the application of prescreening tool to the bone marrow carcinogenicity of chemicals. Normal bone marrow cells were obtained from 8 weeks old male balb/c mice and 2PK, EL4 and M1 were used as representatives of bone marrow cancer cells. Sheared DNA was immunopricipitated with 5-methylcitosine antibody followed by LM (ligation-mediated) PCR. Amplified DNA were labeled with fluorescence and hybridized to mouse 105K methylation chip (Agilent). Total RNA was isolated from each cell and reverse-transcripted to cDNA. Expression of mRNA was analyzed by real time PCR. Sodium bisulfite treated DNA was amplified and pyrosequencing analysis was conducted using PSQ96MA system. We identified commonly hypermethylated genes such as ABI2, FGF3, BCL11a, STAGE2 and hypomethylated genes like SLMO1 and PNMA2 in promoter regions compared to those of normal bone marrow cells. Hypermethylated genes in promoter region also showed reduced mRNA expression except ABI2 and hypomethylated gene, SLMO1, was represented hyperexpression of its mRNA in cancer cells. To validate the result of BCL 11a, we did pyrosequencing analysis of Bcl11a, which results showed similar pattern of our previous microarray data. We expect that this altered methylation genes could be very useful for diagnosis index bone marrow originated cancers in experimental animals and used as prescreening tools for the bone marrow related carcinogenic evaluation of chemicals. 102 DOSE-DEPENDENT SHIFTS IN A VY COAT COLOR DISTRIBUTION FOLLOWING MATERNAL DIETARY EXPOSURE TO BISPHENOL A. O. S. Anderson, M. Nahar, T. R. Jones and D. C. Dolinoy. Environmental Health Science, University of Michigan, Ann Arbor, MI. Environmental exposures and nutritional status in utero influence epigenetic mechanisms shaping disease susceptibility throughout the life-course. Metastable epialleles are alleles variably expressed due to epigenetic modifications established early in development. The murine viable yellow agouti (A vy ) locus is a metastable epiallele that results in coat color varying from yellow (unmethylated) to pseudoagouti (methylated) due to stochastic methylation of cytosine-guanine dinucleotides among isogenic mice. In yellow mice, constitutive ectopic Agouti expression results in adverse effects including diabetes and adult-onset obesity. Bisphenol A (BPA), a high production-volume chemical in polycarbonate plastic and epoxy resins, is found in consumer products such as food and water containers, receipts, and metal can linings. Utilizing the A vy mouse model, we evaluated dose-dependent maternal dietary BPA exposure and its impact on coat color distribution, an epigenetic biosensor for altered DNA methylation status. At d22, A vy /a offspring of mothers exposed to a diet of 50 mg/kg (n=9 litters), 50 mcg/kg (n=7 litters), or 50 ng/kg (n=8 litters) BPA throughout gestation and lactation were visually rated for coat color status. Replicating previously reported data from our group (Dolinoy et. al. PNAS, 2007), maternal dietary exposure to 50 mg/kg shifts the coat color distribution of Avy/a offspring toward the yellow coat color phenotype compared to offspring of mothers consuming a control corn oil diet (n=11 litters; p-value=0.004). Conversely, maternal dietary exposure to 50 mcg/kg or 50 ng/kg BPA displays a significant shift toward the pseudoagouti coat color phenotype compared to a corn oil control diet (p-value=0.0036, and 0.0001, respectively). Thus far these results suggest BPA alters A vy epigenetic regulation in a non-monotonic fashion, indicating varying exposure levels early in development may modify the epigenome, which consequently influences disease susceptibility throughout life. 103 THE UP-REGULATION OF AHR AND STAT1 GENE EXPRESSION IN LONG-TERM ESTROGEN EXPOSED MCF-7 CELLS: POTENTIAL ROLES OF AUTOCRINE SIGNALING AND EPIGENETIC MECHANISMS. N. A. Englert 1, 2 , B. C. Spink 1 and D. C. Spink 1, 2 . 1 Laboratory of Molecular Toxicology, Wadsworth Center, New York State Department of Health, Albany, NY and 2 Department of Environmental Health Sciences, State University of New York at Albany, Albany, NY. The aryl hydrocarbon receptor (AhR) regulates expression of cytochromes P4501A1 and 1B1, enzymes that catalyze metabolism and bioactivation of numerous xenobiotics and endobiotics. Signal transducer and activator of transcription 1 (STAT1) mediates the effects of interferons, regulates expression of immune-response genes, potentiates pro-survival signals, and its elevated expression in tumors appears to provide a growth advantage. We observed that both AhR and STAT1 are up-regulated in long-term estrogen exposed (LTEE) MCF-7 breast cancer cells that were obtained by continuous exposure to 1 nM 17β-estradiol (E2). LTEE cells also showed increased levels of phosphorylated STAT1. To determine the persistence of the up-regulation of STAT1 and AhR expression in LTEE cells, we examined their expression in LTEE cultures after the removal of added E2. Our results indicate that STAT1 expression relies on the continued presence of E2, since total STAT1 levels returned to near control levels after E2 withdrawal, with a half-life of about 9 days. STAT1 expression paralleled the level of activation of the MAP kinase pathway, a known effector of STAT1. Increased steady-state ERK1/2 phosphorylation was observed in LTEE cells, but this decreased after E2 removal. Conversely, the elevated expression of AhR showed no reversion toward control levels after 35 days of E2 withdrawal. The up-regulation of AhR expression was coincident with alterations in histone methylation as determined by chromatin immunoprecipitation, and was reflected in marked changes in AhR-regulated CYP1A1 inducibility. These studies indicate that LTEE alters AhR- and STAT1-regulated processes, and that divergent epigenetic and autocrine signaling mechanisms may be involved in their regulation. 104 EPIGENETIC INACTIVATION OF P16 INK4A GENE IS ASSOCIATED WITH RESISTANCE OF GUERIN CARCINOMAS TO DOXORUBICIN AND CISPLATIN. S. Sarfaraz 1 , S. Shpyleva 1 , I. Todor 2 , N. Yanova 2 , V. Chekhun 2 and I. Pogribny 1 . 1 Biochemical Toxicology, NCTR/FDA, Jefferson, AR and 2 Oncology and Radiobiology, R.E. Kavetsky Institute of Experimental Pathology, Kyiv, Ukraine. Sponsor: V. Tryndyak. Acquired drug resistance is a major clinical obstacle in the treatment of cancer patients. Therefore, understanding the underlying molecular mechanisms associated with its development is of prime importance. In the present study, we examined the role of epigenetic alterations in transplantable Guerin carcinoma resistant to either Doxorubicin (DOX) or Cisplatin (cisDDP), two cancer chemotherapeutic drugs with different modes of action. Despite this difference, Dox- and cisDDP-resistant Guerin tumors displayed similar alterations in expression of most common cancerrelated genes. These changes include down-regulation of Tp53, Pten, Brca1, and Cdkn2a(p16 INK4a ) genes and up-regulation of Fos, Vegfa, Vegfc, Plaur, and S100a4 genes. Additionally, both drug-resistant Guerin tumors were characterized by similar epigenetic changes showing pronounced DNA hypermethylation. This was evidenced by the 63% increase in gene-specific CpG island methylation in resistant SOT 2011 ANNUAL MEETING 21
Page 1 and 2: The Toxicologist Supplement to Toxi
Page 3 and 4: The Toxicologist Supplement to Toxi
Page 5 and 6: 1 BIODEGRADABLE MATERIALS FOR TISSU
Page 7 and 8: that genetic toxicology data are ge
Page 9 and 10: well-orchestrated lung inflammation
Page 11 and 12: scribed in the literature. We have
Page 13 and 14: years ago). We will illustrate how
Page 15 and 16: involved in the biodegradation proc
Page 17 and 18: stem cells but rather a treatment i
Page 19 and 20: additional compound showed agreemen
Page 21 and 22: 82 COMPARISON OF 3H-THYMIDINE INCOR
Page 23: irritants. While in practice these
Page 27 and 28: 109 CD4+ T CELL INTRINSIC TNF RECEP
Page 29 and 30: 118 TO STUDY THE SIGNAL TRANSDUCTIO
Page 31 and 32: PAHs, such as dioxins, are prevalen
Page 33 and 34: containing substituents and/or hydr
Page 35 and 36: 146 COMPUTATIONAL MODELING FOR QT P
Page 37 and 38: suggest that the combination of too
Page 39 and 40: 164 TRANSLOCATOR PROTEIN (18 KDA) (
Page 41 and 42: function as a metal binding protein
Page 43 and 44: laboratory has demonstrated that NR
Page 45 and 46: known. The aim of this study was to
Page 47 and 48: from 5 to 28 days in duration) in e
Page 49 and 50: positive cells, caspase-3 activatio
Page 51 and 52: creased level in the 46 kDa preproe
Page 53 and 54: invasiveness at concentrations repr
Page 55 and 56: thracene (DMBA,50 μg in acetone, a
Page 57 and 58: 247 CO-CARCINOGENESIS OF N, N- DIET
Page 59 and 60: sponds to the endosomal dsRNA that
Page 61 and 62: ODD in both WT (maximum 177% of con
Page 63 and 64: Lastly, using p53siRNA cells, p53 w
Page 65 and 66: its receptor Mpl to exert its funct
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Page 69 and 70: lunar surface presented potential h
Page 71 and 72: lar about cellular export mechanism
Page 73 and 74: DNA in the kidney medulla, grandula
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5.00 and 7.50 mg/kg/day by oral gav
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events and carcinogenesis. Here we
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tinization of cells of the hair fol
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358 CHARACTERIZATION OF GENOME-WIDE
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RNAi were also performed to identif
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376 A FUNCTIONAL CROSSTALK BETWEEN
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UGT1A gene induction, while this re
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tivity, specifically peroxisome pro
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and cytotoxic effects; however, its
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histone deacetylase that is necessa
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ment. Paradoxically, buthionine sul
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drug leflunomide and its major (A77
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442 GENE EXPRESSION AND MORPHOLOGIC
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451 INHIBITION OF THE MITOCHONDRIAL
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460 SULFORAPHANE PREVENTS ACETAMINO
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drophilic/lipophilic balance. Other
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pharmacokinetic and toxicological p
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489 USE OF ‘OMICS DATA TO IMPROVE
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498 APPLICATION OF AGE-SPECIFIC ADJ
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507 A DOSE VOLUME TOLERABILITY STUD
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involved the use of an acute inflam
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sorption in the gastrointestinal (G
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(ABC) transporters actively transpo
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545 BEHAVIORAL EFFECTS OF REPIN IN
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a blood pressure phenotype that res
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and inhalation exposure system that
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and lethality associated with these
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position, on vascular reactivity an
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therefore more accurate and reprodu
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commercial chrysotile product that
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elative to their controls. ST-depre
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ats. The majority of the studies fo
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in the China Jintan Child Cohort St
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corneum thickness, cellular epiderm
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645 EVALUATION OF THE IN VITRO EPIS
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654 TCDD ADSORBED ONTO NATURAL AND
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tion revealed no test article-relat
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671 INFLAMMATION AND TISSUE DAMAGE
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model, ethanol was found to inhibit
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689 ENHANCED SUPPRESSIVE FUNCTION O
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NAC + LPS yielded different levels
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707 LIFE-STAGE PBPK MODELS FOR MULT
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downstream of the apical endpoint o
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726 UPDATED ALUMINUM PHARMACOKINETI
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global parameter sensitivity analys
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and renal inflammation induced by 2
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754 PLASMA, URINE, AND TISSUE CONCE
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cently characterized transporter OA
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exposure system was developed from
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lood cell mass and decrease in urin
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practical alternatives to MC in non
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imals dosed with 167 mg/kg THU alon
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and organ weights, clinical signs a
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yet is induced in most bladder and
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830 RISK ASSESSMENT OF THE SPILL: C
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knowledgebase creation. Results are
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852 UNDERSTANDING STRUCTURAL AND PH
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for integrating epidemiology and an
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motor activity, including age of th
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y partial purification of urine (fr
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pacity for self-renewal and may dif
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sue. The depth of our analysis led
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910 IMPLEMENTING CALIFORNIA’S GRE
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concentrations in six tissues and b
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934 THE FDA’S LIVER TOXICITY KNOW
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943 GENOME-WIDE DNA METHYLATION DIF
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membrane localization and subsequen
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trols, respectively. Subtoxic and t
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survival using both smoking regimes
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as non-, weak, moderate, or strong
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988 NNK-INDUCED CYTOKINE ALTERATION
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group (one-way ANOVA, p90 % viabili
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ered as an organ involved in xenobi
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Transport of CPZ across the Caco-2
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estrous cycle and sexual behavior d
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mRNA expression levels. Collectivel
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1043 THE EFFECTS OF ENDOCRINE DISRU
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1052 MONO-2-ETHYLHEXYL PHTHALATE IN
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Results: MC was variable within and
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UtSMCs. Phosphorylation of FoxO1 wa
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nonpregnant and pregnant diabetic m
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1089 PFOA-INDUCED LIVER EFFECTS IN
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events in the liver. AZD9056 was ev
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The peppermint oil caused a concent
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OA did not affect food consumption.
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1126 PERSISTENT DEVELOPMENTAL ARYLH
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1135 BACH2 BINDING TO Prdm1 AS A ME
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The purpose of this project was to
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one marrow. Since Chk1 is an attrac
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1163 THE MRNA AND MIRNA PROFILE OF
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have now compared the IC50 values b
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1181 ELUCIDATION OF FACTORS DETERMI
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enced by pre-exposure to cigarette
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if abnormal PF was associated with
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weight (P=0.016) and small for gest
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portant cause of death, compared to
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posure groups. However, the differe
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Naphthalene is routinely analyzed i
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1245 SEASONAL CHARACTERIZATION OF H
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1255 URINARY T, T MUCONIC ACID LEVE
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modating a reliable data evaluation
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enzoquinone generate ROS and arylat
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teins (e.g. C3, 4, and 5, APOB, VDB
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1293 TRANSFORMING GROWTH FACTOR BET
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mation was decreased to the same le
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1312 EVALUATION OF THE SENSITIVITY
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luted OFR and CRL. Culture media ex
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urinary TCPy levels, blood and brai
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activity. The dose-response curves
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mice, each with 4 dose groups. One
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exposure to both ATR and DACT has a
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third tetratricopeptide repeats (TP
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7d. 28d after TMT injury there was
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subunits. Each cell type was treate
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1394 COMPARATIVE EFFECTS OF METHYLM
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1403 GENOTOXICITY AND PRE-NEOPLASTI
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vated only in high-dose-treated ani
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1421 DOSE-RESPONSE OF NAPHTHALENE-I
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cisplatin; 1.2-, 1.9- and 2.9-fold
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Day 11 and started to recover on Da
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1448 DEVELOPMENT OF A METHOD FOR QU
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1457 GLOBAL GENE PROFILING REVEALS
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cluding mouse and human macrophage,
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model of lung inflammation and host
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1484 NANOTOXICOLOGY AND NANOHEALTH
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throughput in vitro approach was us
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1502 IMMUNOLOGICAL ASPECTS OF AN AN
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(CIA) and the Streptococcal cell wa
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sitizers were 100% concordant among
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1530 MINIMAL RISK LEVELS FOR STYREN
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ical groups in the field of regulat
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vitro with this potentially insect-
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their performance on toxicological
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need for a better understanding of
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1577 AN IN VITRO MODEL SYSTEM FOR A
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gene expression post-transcriptiona
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1595 GENE EXPRESSION PROFILE OF RAT
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to confirm a hepatotoxic property o
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1613 AN INVESTIGATION OF THE CLEARA
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its nuclear translocation was reduc
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were collected from TK animals at d
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egulated targets were selected for
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U/L after tetracycline. Minocycline
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peri-pubertal FasL-/- mice show a d
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showed similar levels of apoptosis
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1676 TWO BIOMARKERS FOR EVALUATION
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motifs selected. This system was ap
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1693 VOC SERUM LEVELS IN THE GENERA
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1702 DOES THE CLOCK MAKE THE POISON
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those with high nickel content are
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isk assessment. However, unique cha
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model of APAP metabolism and glutat
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logically & morphologically similar
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posure, blood chemistry was analyze
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elated to oxidative stress by measu
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ostasis), but work is needed to tra
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tokine products during carcinogenes
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ways as chemical stressors and, the
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toxicity of nanomaterials relates s
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1815 MEASURING COMPOUND SELECTIVITY
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1825 EFFECTS OF METABOLISM BY INTES
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cyanoacetic acid increased 2-3 fold
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1845 IS THE PROMISCUITY OF THE ARYL
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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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