The Toxicologist - Society of Toxicology

More documents

Recommendations

Info

1371 PON1 Q192R POLYMORPHISM ANALYSIS IN SOUTHERN CARDIAC PATIENTS. M. Dail, A. Crow, H. Coombes, E. Meek, H. Chambers and J. Chambers. Center for Environmental Health Sciences, Mississippi State University, MS State, MS. Paraoxonase (PON1) hydrolyzes paraoxon, the active metabolite of the insecticide parathion. The human PON1 gene has several single nucleotide polymorphisms (SNPs). The SNP involving a glutamine (Q) to arginine (R) substitution at codon 192 may be associated with the ability of PON1 to hydrolyze oxidized lipids, which protects against atherosclerosis. The question of whether the Q192R polymorphism is associated with cardiac disease is still open. Since southerners have the country’s highest rate of cardiac disease, we collected blood and demographic data from 197 patients in a Mississippi cardiovascular clinic to compare the functional genotypes derived from serum PON1 hydrolytic activity to parameters of cardiac health. The multivariable model generated suggested that functional genotypic differences were insignificant compared to classic factors of atherosclerotic risk, but many of the patients were difficult to sort. To increase clarity, we sorted patients by their actual genotype and reexamined associations. Genomic DNA was isolated from blood and the 192 codon area was amplified by PCR. Since there is an AlwI restriction site at codon 192, the QQ, RR, and QR SNPs yield different digest patterns. The prior work found that Caucasians most often display the QQ functional genotype while African Americans have the RR functional genotype. This was confirmed. Other significant relationships: QQs are more often smokers whereas RRs are nonsmokers. QQs and RRs are more likely to have a family history of cardiac disease than QRs. HDL levels of RR patients were found to be significantly higher (P = 0.012) than those having a QQ genotype. RR patients were significantly younger (P = 0.02) than either QR or QQ patients. No significant relationships were seen between genotype and personal history of cardiac disease, statin use, or diabetes. No significant differences were seen among the three genotypes with regard to triglycerides, height, weight, waist size, LDL, or total cholesterol (Support NIHES015170) 1372 ANALYSIS OF POLYMORPHISMS OF ASTHMATIC CHILDREN FROM COAHUILA, MEXICO EXPOSED TO ENVIRONMENTAL TOBACCO SMOKE (ETS). B. Muñoz-Soto 1 , B. S. Barrón-Vivanco 1 , A. López-Moya 1 , I. Romero-Toledo 1 , C. López-Campos 2 , J. J. Magaña-Aguirre 3 and A. Albores 1 . 1 Toxicology, Cinvestav- IPN, México, Mexico, 2 Pediatrics, UMAE-IMSS 71, Torreon, Coahuila, Mexico and 3 Human Genetics, INR, Mexico City, Mexico. Recent studies argue that asthma prevalence in Mexico has increased 15% in the last 10 years; the constant exposure to allergens and environmental pollutants such as tobacco smoke is considered as one of the principal etiological factors. The vast majority of asthmatics are children; therefore, the aim of this study was to investigate the association between ETS exposure and some genetic polymorphism in asthmatic children. Our pilot study includes a population from Torreon, Coahuila, located in Northeast Mexico. Study groups included asthmatic children diagnosed according to ISAAC parameters (n=114) and a control group (n=100). These groups were subdivided in ETS-exposed children and non-exposed children, according to the parent’s smoking habits. Spirometric studies and urine cotinine analysis were also performed. Real time PCR assays were used for genotyping IL13 (rs20541 and rs1800925), GSTP1 (rs1695), TNF (rs18000629) TSLP (rs1837253), ADBR2 (rs1042713) polymorphisms whereas conventional PCR was used for genotyping CYP1A1 (rs1048943). Our findings indicate that smoker’s children showed higher cotinine levels than controls. On the other hand, we found no association between variants of IL13, GSTP1, TNF or CYP1A1 with asthma and exposure to ETS, however, other studies have shown this association. Remarkably, girls seems to be more susceptible to develop asthma (p=0.057); a strong association with TSLP (rs1837253) (p=0.0271) and marginal associations of ADBR2 (rs1042713) (p=0.099) with asthma was also observed. In addition, the TSLP mutated allele in asthmatic girls was also associated (p=0.072). This is the first study of asthma-related polymorphisms in Mexican children exposed to ETS. 294 SOT 2011 ANNUAL MEETING 1373 CYP1A1*2C, EPHX1T113H, EPHX1H139R, AND NQO1*2 POLYMORPHISMS ARE INVOLVED IN THE GENETIC DAMAGE CAUSED IN CHILDREN EXPOSED TO PAHS AND BENZENE. M. Sánchez-Guerra 1 , N. A. Pelallo-Martínez 2 , F. Díaz-Barriga 2 , L. Carrizales- Yáñez 2 , L. Hernández-Cadena 3 , M. E. Gonsebatt 4 and B. Quintanilla-Vega 1 . 1 Toxicology Department, Cinvestav-IPN, Mexico City, Mexico, 2 Faculty of Medicine, UASLP, San Luis Potosí, Mexico, 3 National Institute of Public Health, Cuernavaca, Morelos, Mexico and 4 IIB, UNAM, Mexico City, Mexico. Polycyclic aromatic hydrocarbons (PAHs) and benzene are pollutants of urban cities and are considered genotoxic. Both compounds are metabolized and some enzymes such as CYP1A1 and CYP1B1 (activation) and NQO1 and GSTM (deactivation) and EPHX1 with both activities are polymorphic. We performed a crosssectional study in children (6 to 10 years old, n=77) from primary schools located in the vicinities of the main industrial complex of Coatzacoalcos County, Veracruz, Mexico, an industrialized area with 80% of country’s petrochemical activity, to evaluate the genetic damage of PAHs and benzene exploring the role of some metabolizing enzyme polymorphisms. Urinary 1-OHP levels and trans, trans muconic acid (t,t MA) as biomarkers of PAHs and benzene exposure, respectively, were determined by HPLC and CYP1A1*2C, CYP1B1*3, EPHX1T113H, EPHX1H139R, NQO1*2 and GSTM1*0 genetic polymorphisms by real time or conventional PCR. DNA damage was evaluated in lymphocytes by the Comet assay (tail moment). Thirteen percent of children had 1-OHP levels higher than 1.4 μmol/mol creatinine (NOAEL) and 32% had higher t,t-MA levels than the biological exposure index in the workplace (500 μg/g creatinine). DNA damage was significantly associated only with 1-OHP levels: children with 1-OHP levels above 1.4 μmol/mol creatinine showed a 23% increase of DNA damage, adjusted by t,t-MA (p=0.027). On the other hand, the DNA damage was higher in CYP1A1*2C homozygous children with 1-OHP levels above the NOAEL (54%, p=0.032); while children carrying one allele of NQO1*2 or of EPHX1H139R polymorphisms had lower DNA damage (-37%, p=0.039 and -49%, p=0.007, respectively). These results suggest that polymorphisms of the studied metabolizing enzymes may have an important role in the development of adverse effects of urban environmental exposed children. 1374 USING OF PCR-RFLP OF CYTOCHROME B GENE FOR HAIR IDENTIFICATION IN HUMAN AND SOME NON- DOMESTIC ANIMALS. M. H. Ghoneim, A. A. Abou-Hadeed, A. M. Alkelch and M. R. Awad-allah. Toxicology&Forensic Medicine, Zagazig University, Zagazig, Egypt. PCR and PCR-RFLP methods were used to differentiate between human and some non domestic animals. DNA from hair was extracted to amplify a mitochondrial cytochrome b (cyt b) gene segment (358 bp) using universal primer followed by agarose gel electrophoresis. The total cyt b segment was digested with 4 restriction endonucleases,( Alu I, HaeIII, HinfI and Taq I ) and the resulting fragments were resolved through electrophoresis. The different specific electrophoretic patterns and total restriction fragments were observed in each of the studied species. The restriction enzyme Alu I yielded 2 fragments of different sizes in all animal species. while no cleavage was observed in human hair. The digestion of PCR products with HaeIII restriction enzyme revealed restriction fragments patterns of different sizes in human and all species except in Bear. Using of HinfI restriction enzyme produced 2 or 3 fragments of different sizes for human and all species except Lama. When the amplified cyt b segment was digested by Taq I restriction enzyme it gave 2 bands of different sizes except Barbary sheep. There was variation in size of segments in human and different species. 1375 STEM CELL REPONSES OF MURINE HIPPOCAMPUS FOLLOWING TRIMETHYLTIN INTOXICATION. B. C. Weig, K. R. Reuhl and H. E. Lowndes. Pharmacology & Toxicology, Rutgers University, Piscataway, NJ. Stem cells from the developing mammalian brain persist in adults in the subventricular zone (SVZ) and the hippocampal subgranular zone (SGZ). The response of SVZ and SGZ stem cells to hippocampal injury was studied in two-month old male C3H mice treated with trimethyltin (TMT). The fluorescent marker spDiI was injected unilaterally into the lateral ventricle of mice to label migrating SVZ cells. Bromodeoxyuridine (BrdU) was administered (80 mg/kg; ip) to label proliferating progenitor cells prior to treatment with TMT (2.7 mg/kg; ip). Sagittal brain sections taken 7 or 28d later revealed spDiI+ cells in the hippocampus of control mice at 7d, with a trend toward an increased number cells at 28d (p=0.0523). TMT injury had no effect on the number of BrdU+ or spDiI+ cells in the hippocampus at
7d. 28d after TMT injury there was a 4-fold increase in spDiI+ cells in the dentate gyrus granular and subgranular zone. Markers for astrocytes (GFAP) or neurons (NeuN) rarely co-localized suggesting the migrated spDiI+ cells remain in an undifferentiated state. TMT injury prevented the physiological loss of newly born (BrdU+) cells after 28d, either by increasing cell survival or recruitment of BrdU+ cells from the SVZ. Less than 15% of BrdU+ cells co-labeled with spDiI. To assess the role of cell proliferation in recovery from injury, mitosis was reduced by cranial exposure to 10gy gamma radiation 48hr prior to TMT injection, decreasing newlyborn cells by 70%. TMT-induced tremors increased in severity and duration in irradiated mice, but tremors in all mice ceased by 5d post-TMT. TMT exposure caused prominent thrombomodulin staining in the parenchyma of the hippocampus dentate gyrus, indicating extravasation of blood-borne factors specifically at the site of injury. Data suggest that repair/recovery from TMT injury may include migration of SVZ cells into the injury site in addition to increased proliferation and survival of new neurons produced from endogenous hippocampal stem cells. Supported by ES011256, ES05022, and ES07148. 1376 EFFECTS OF DIFFERENT FORMS OF COPPER ON HUMAN CNS DERIVED CELL LINES. S. S. Shaligram and A. Campbell. Pharmaceutical Sciences, Western University of Health Sciences, Pomona, CA. Copper is considered an essential metal for living organisms. However, excess copper is toxic owing to its ability to generate reactive oxygen species (ROS). This metal is directly linked to Menkes and Wilson’s diseases. It is also implicated in agerelated neurodegenerative disorders such as Alzheimer’s disease. Copper is known to cause oxidative stress in the CNS. The purpose of this study was to study cellular response to soluble (copper sulfate) or insoluble (copper oxide) forms of this redoxactive metal. We examined the formation of reactive oxygen species in human cell lines derived from the CNS after dosing them with different concentrations (0.5 μM- 625 μM) of copper sulfate or copper oxide. We assessed cell number and ROS formation after either 4 hr or 24 hr of copper exposure. In the SK-N-SH cells (neuronal), the number of cells decreased on exposure to the highest concentration of copper sulfate after 4 hr. After 24 hr exposure, the cell number increased at lower doses but decreased nonsignificantly at higher doses. With copper oxide, we saw a dose-dependent decrease in cell number after 4 hr and 24 hr. In A-172 cells (glioblastoma), the cell number decreased at higher doses with copper sulfate after 4 hr but showed no change at 24 hr. Exposure to copper oxide caused a dose-dependent decrease in cell number at both time points but the effect was more pronounced after 24 hr exposure. The neuronal cells showed a decrease in ROS formation after 24 hr with copper sulfate but showed no change after 4 hr, while the glioblastoma cells showed an increase in ROS formation at the higher concentrations of copper oxide after 24 hr exposure. Based on these results, we conclude that both forms of copper have some effect on the given cell lines but the response to copper oxide is more pronounced. 1377 MECHANISM OF BRAIN COPPER (CU) TRANSPORT AND ACCUMULATION: INFLUENCE OF IRON DEFICIENCY. A. D. Monnot 1 , S. Ho 1 , G. Robinson 2 , Y. Pushkar 2 and W. Zheng 1 . 1 Health Sciences, Purdue University, West Lafayette, IN and 2 Physics, Purdue University, West Lafayette, IN. Cu and iron (Fe) are essential for brain development and metabolism. Previous studies from this lab have shown an inverse physiologic relationship between Fe and Cu in the central nervous system. Despite its critical role in normal brain function, knowledge on Cu transport, distribution, homeostatic regulation, and the impact of Fe status, remains largely unexplored. This study was designed to investigate the regulation of Cu transport by Fe status at the blood-brain barrier (BBB) and bloodcerebrospinal fluid barrier (BCB), as well as the distribution of Cu in the brain. Rats were divided into 3 groups with special diets at libertum for 4 weeks: control (35 mg Fe/kg), Fe deficient (FeD) (3-5 mg Fe/kg), and Fe overload (FeO) (20 g carbonyl Fe/kg) groups. Serum Fe status, either FeD or FeO, was confirmed by total Fe, unsaturated Fe binding capacity, total Fe binding capacity, and transferrin saturation in serum. In situ brain perfusion of 64Cu demonstrated that the rate of Cu transport was significantly faster in brain parenchyma (+92%) and capillaries (+500%) in FeD rats than those in controls. In contrast, FeO treatment significantly reduced the rate of 64Cu transported into brain parenchyma (~50% of controls). Additionally, Cu clearance from the CSF was greater in FeD than in control animals as demonstrated by ventriculo-cisternal brain perfusion, suggesting an increased Cu uptake from the CSF by the BCB. Results from mRNA and protein expression studies indicated that FeD was responsible for the up-regulation of DMT1, but not CTR1, at both the BBB and BCB, which may contribute to the enhanced Cu uptake found at the barriers. X-ray fluorescence imaging indicated Cu accumulation in the subventricular zone (SVZ) of the lateral ventricles. An elevated Cu level (+25%), although not statistically significant, was found in the SVZ of FeD. These results suggest that DMT1 regulation at the brain barriers, but not at SVZ, contribute to Cu accumulation and regulation during FeD in the brain. (Supported by NIH/RO1-ES008146) 1378 PERSISTING NEUROCHEMICAL EFFECTS OF DEVELOPMENTAL COPPER EXPOSURE IN WILDTYPE AND METALLOTHIONEIN 1 AND 2 KNOCKOUT MICE. A. Petro 1 , H. Sexton 1 , C. Miranda 1 , A. Rastogi 1 , J. H. Freedman 3 and E. D. Levin 1, 2 . 1 Psychiatry, Duke University Medical Center, Durham, NC, 2 Integrated Toxicology and Environmental Health Program, Duke University, Durham, NC and 3 NIEHS, Research Triangle Park, NC. Metallothioneins are small proteins, which are crucial for the distribution of heavy and transition metals. This series of studies was conducted to determine the role of metallothioneins on metal-induced neurotoxicity during development. Previously, we found that knockout of MT 1 and 2 potentiated the cognitive impairment caused by developmental mercury exposure. The current study examined the neurocognitive effects of developmental copper supplementation. Wildtype and MT 1 and 2 knockout mice (MTKO) were given 10 or 50 mg/l of supplemental copper during gestation and until weaning. Mice of both genotypes with no added copper served as controls. When the mice were young adults they were trained for 18 sessions on the win-shift 8-arm radial maze test of spatial learning and memory. Male MTKO mice with no added copper were significantly impaired on radial-arm maze choice accuracy relative to wildtype controls. This MTKO-induced impairment was significantly attenuated by addition of 10 mg/l but not 50 mg/l of copper supplementation during development. Neurochemical analyses showed that MTKO caused a significant overall increase in serotonin in all of the regions studied: the frontal cortex, posterior cortex, hippocampus, striatum, midbrain, and brainstem. MTKO also caused a significant increase in norepinepherine in the brainstem and hippocampus. In wildtype mice, copper supplementation during development caused a significant decline in dopamine and norepinepherine levels in the midbrain and dopamine in the frontal cortex. These effects were blocked by knockout of MT 1 and 2. (Supported by NIH ES10356) 1379 PERSISTENT OLFACTORY DEFICITS FOLLOWING INTRANASAL CADMIUM EXPOSURE CAN BE REHABILITATED BY TRAINING ON AN OLFACTORY DETECTION TASK. D. J. Turkel, A. H. Moberly, L. Czarnecki and J. P. McGann. Psychology Department, Rutgers University, Piscataway, NJ. We have previously shown that acute intranasal exposure to cadmium disrupts olfactory nerve function, including a large decrease in odorant-evoked neurotransmitter release, reduced innervation of the olfactory bulb, and profound impairment on an olfactory detection task in the mouse. These deficits persist for at least four weeks. However, some olfactory nerve function remains intact following cadmium exposure, which could in principle be sufficient to detect an odorant. We hypothesized that post-exposure olfactory training could potentially rehabilitate detection performance. C57Bl/6 mice were trained to perform an odorant-guided go/no-go odor detection task in which they sampled at an odor-port and then received a sucrose reward for a nose poke in a dipper port if and only if the odorant was presented. Incorrect responses were punished by a lengthened intertrial interval. After mice achieved criterion performance, they were anesthetized and received bilateral intranasal instillations of either 20 μg cadmium/side or vehicle control. They were randomly assigned to either a 2-day delay or 10-day delay group. Cadmium-exposed mice tested at either time point were profoundly impaired on the detection task, with an average d’ of about 0.15 in both groups. After testing, the worst performing mice from the 2-day group were trained daily on the discrimination task until they again achieved criterion performance. Remarkably, by Day 10 this group’s performance was not only significantly better than that of the untrained group at Day 10, but comparable to baseline performance. Rehabilitated mice tested without odorants exhibited no discrimination, confirming that they were indeed using their damaged olfactory systems to perform the task. This recovery of detection ability suggests that downstream brain regions can successfully learn to interpret olfactory degraded sensory input. In addition to informing potential therapies, these data suggest that rapid sensory learning could potentially mask the effects of serious pathology. SOT 2011 ANNUAL MEETING 295
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 and 24:
irritants. While in practice these
Page 25 and 26:
alleles are especially vulnerable t
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
Page 67 and 68:
294 LOW LEVEL OF LEAD CAN INDUCE PH
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
Page 75 and 76:
5.00 and 7.50 mg/kg/day by oral gav
Page 77 and 78:
events and carcinogenesis. Here we
Page 79 and 80:
tinization of cells of the hair fol
Page 81 and 82:
358 CHARACTERIZATION OF GENOME-WIDE
Page 83 and 84:
RNAi were also performed to identif
Page 85 and 86:
376 A FUNCTIONAL CROSSTALK BETWEEN
Page 87 and 88:
UGT1A gene induction, while this re
Page 89 and 90:
tivity, specifically peroxisome pro
Page 91 and 92:
and cytotoxic effects; however, its
Page 93 and 94:
histone deacetylase that is necessa
Page 95 and 96:
ment. Paradoxically, buthionine sul
Page 97 and 98:
drug leflunomide and its major (A77
Page 99 and 100:
442 GENE EXPRESSION AND MORPHOLOGIC
Page 101 and 102:
451 INHIBITION OF THE MITOCHONDRIAL
Page 103 and 104:
460 SULFORAPHANE PREVENTS ACETAMINO
Page 105 and 106:
drophilic/lipophilic balance. Other
Page 107 and 108:
pharmacokinetic and toxicological p
Page 109 and 110:
489 USE OF ‘OMICS DATA TO IMPROVE
Page 111 and 112:
498 APPLICATION OF AGE-SPECIFIC ADJ
Page 113 and 114:
507 A DOSE VOLUME TOLERABILITY STUD
Page 115 and 116:
involved the use of an acute inflam
Page 117 and 118:
sorption in the gastrointestinal (G
Page 119 and 120:
(ABC) transporters actively transpo
Page 121 and 122:
545 BEHAVIORAL EFFECTS OF REPIN IN
Page 123 and 124:
a blood pressure phenotype that res
Page 125 and 126:
and inhalation exposure system that
Page 127 and 128:
and lethality associated with these
Page 129 and 130:
position, on vascular reactivity an
Page 131 and 132:
therefore more accurate and reprodu
Page 133 and 134:
commercial chrysotile product that
Page 135 and 136:
elative to their controls. ST-depre
Page 137 and 138:
ats. The majority of the studies fo
Page 139 and 140:
in the China Jintan Child Cohort St
Page 141 and 142:
corneum thickness, cellular epiderm
Page 143 and 144:
645 EVALUATION OF THE IN VITRO EPIS
Page 145 and 146:
654 TCDD ADSORBED ONTO NATURAL AND
Page 147 and 148:
tion revealed no test article-relat
Page 149 and 150:
671 INFLAMMATION AND TISSUE DAMAGE
Page 151 and 152:
model, ethanol was found to inhibit
Page 153 and 154:
689 ENHANCED SUPPRESSIVE FUNCTION O
Page 155 and 156:
NAC + LPS yielded different levels
Page 157 and 158:
707 LIFE-STAGE PBPK MODELS FOR MULT
Page 159 and 160:
downstream of the apical endpoint o
Page 161 and 162:
726 UPDATED ALUMINUM PHARMACOKINETI
Page 163 and 164:
global parameter sensitivity analys
Page 165 and 166:
and renal inflammation induced by 2
Page 167 and 168:
754 PLASMA, URINE, AND TISSUE CONCE
Page 169 and 170:
cently characterized transporter OA
Page 171 and 172:
exposure system was developed from
Page 173 and 174:
lood cell mass and decrease in urin
Page 175 and 176:
practical alternatives to MC in non
Page 177 and 178:
imals dosed with 167 mg/kg THU alon
Page 179 and 180:
and organ weights, clinical signs a
Page 181 and 182:
yet is induced in most bladder and
Page 183 and 184:
830 RISK ASSESSMENT OF THE SPILL: C
Page 185 and 186:
knowledgebase creation. Results are
Page 187 and 188:
852 UNDERSTANDING STRUCTURAL AND PH
Page 189 and 190:
for integrating epidemiology and an
Page 191 and 192:
motor activity, including age of th
Page 193 and 194:
y partial purification of urine (fr
Page 195 and 196:
pacity for self-renewal and may dif
Page 197 and 198:
sue. The depth of our analysis led
Page 199 and 200:
910 IMPLEMENTING CALIFORNIA’S GRE
Page 201 and 202:
concentrations in six tissues and b
Page 203 and 204:
934 THE FDA’S LIVER TOXICITY KNOW
Page 205 and 206:
943 GENOME-WIDE DNA METHYLATION DIF
Page 207 and 208:
membrane localization and subsequen
Page 209 and 210:
trols, respectively. Subtoxic and t
Page 211 and 212:
survival using both smoking regimes
Page 213 and 214:
as non-, weak, moderate, or strong
Page 215 and 216:
988 NNK-INDUCED CYTOKINE ALTERATION
Page 217 and 218:
group (one-way ANOVA, p90 % viabili
Page 219 and 220:
ered as an organ involved in xenobi
Page 221 and 222:
Transport of CPZ across the Caco-2
Page 223 and 224:
estrous cycle and sexual behavior d
Page 225 and 226:
mRNA expression levels. Collectivel
Page 227 and 228:
1043 THE EFFECTS OF ENDOCRINE DISRU
Page 229 and 230:
1052 MONO-2-ETHYLHEXYL PHTHALATE IN
Page 231 and 232:
Results: MC was variable within and
Page 233 and 234:
UtSMCs. Phosphorylation of FoxO1 wa
Page 235 and 236:
nonpregnant and pregnant diabetic m
Page 237 and 238:
1089 PFOA-INDUCED LIVER EFFECTS IN
Page 239 and 240:
events in the liver. AZD9056 was ev
Page 241 and 242:
The peppermint oil caused a concent
Page 243 and 244:
OA did not affect food consumption.
Page 245 and 246:
1126 PERSISTENT DEVELOPMENTAL ARYLH
Page 247 and 248: 1135 BACH2 BINDING TO Prdm1 AS A ME
Page 249 and 250: The purpose of this project was to
Page 251 and 252: one marrow. Since Chk1 is an attrac
Page 253 and 254: 1163 THE MRNA AND MIRNA PROFILE OF
Page 255 and 256: have now compared the IC50 values b
Page 257 and 258: 1181 ELUCIDATION OF FACTORS DETERMI
Page 259 and 260: enced by pre-exposure to cigarette
Page 261 and 262: if abnormal PF was associated with
Page 263 and 264: weight (P=0.016) and small for gest
Page 265 and 266: portant cause of death, compared to
Page 267 and 268: posure groups. However, the differe
Page 269 and 270: Naphthalene is routinely analyzed i
Page 271 and 272: 1245 SEASONAL CHARACTERIZATION OF H
Page 273 and 274: 1255 URINARY T, T MUCONIC ACID LEVE
Page 275 and 276: modating a reliable data evaluation
Page 277 and 278: enzoquinone generate ROS and arylat
Page 279 and 280: teins (e.g. C3, 4, and 5, APOB, VDB
Page 281 and 282: 1293 TRANSFORMING GROWTH FACTOR BET
Page 283 and 284: mation was decreased to the same le
Page 285 and 286: 1312 EVALUATION OF THE SENSITIVITY
Page 287 and 288: luted OFR and CRL. Culture media ex
Page 289 and 290: urinary TCPy levels, blood and brai
Page 291 and 292: activity. The dose-response curves
Page 293 and 294: mice, each with 4 dose groups. One
Page 295 and 296: exposure to both ATR and DACT has a
Page 297: third tetratricopeptide repeats (TP
Page 301 and 302: subunits. Each cell type was treate
Page 303 and 304: 1394 COMPARATIVE EFFECTS OF METHYLM
Page 305 and 306: 1403 GENOTOXICITY AND PRE-NEOPLASTI
Page 307 and 308: vated only in high-dose-treated ani
Page 309 and 310: 1421 DOSE-RESPONSE OF NAPHTHALENE-I
Page 311 and 312: cisplatin; 1.2-, 1.9- and 2.9-fold
Page 313 and 314: Day 11 and started to recover on Da
Page 315 and 316: 1448 DEVELOPMENT OF A METHOD FOR QU
Page 317 and 318: 1457 GLOBAL GENE PROFILING REVEALS
Page 319 and 320: cluding mouse and human macrophage,
Page 321 and 322: model of lung inflammation and host
Page 323 and 324: 1484 NANOTOXICOLOGY AND NANOHEALTH
Page 325 and 326: throughput in vitro approach was us
Page 327 and 328: 1502 IMMUNOLOGICAL ASPECTS OF AN AN
Page 329 and 330: (CIA) and the Streptococcal cell wa
Page 331 and 332: sitizers were 100% concordant among
Page 333 and 334: 1530 MINIMAL RISK LEVELS FOR STYREN
Page 335 and 336: ical groups in the field of regulat
Page 337 and 338: vitro with this potentially insect-
Page 339 and 340: their performance on toxicological
Page 341 and 342: need for a better understanding of
Page 343 and 344: 1577 AN IN VITRO MODEL SYSTEM FOR A
Page 345 and 346: gene expression post-transcriptiona
Page 347 and 348: 1595 GENE EXPRESSION PROFILE OF RAT
Page 349 and 350:
to confirm a hepatotoxic property o
Page 351 and 352:
1613 AN INVESTIGATION OF THE CLEARA
Page 353 and 354:
its nuclear translocation was reduc
Page 355 and 356:
were collected from TK animals at d
Page 357 and 358:
egulated targets were selected for
Page 359 and 360:
U/L after tetracycline. Minocycline
Page 361 and 362:
peri-pubertal FasL-/- mice show a d
Page 363 and 364:
showed similar levels of apoptosis
Page 365 and 366:
1676 TWO BIOMARKERS FOR EVALUATION
Page 367 and 368:
motifs selected. This system was ap
Page 369 and 370:
1693 VOC SERUM LEVELS IN THE GENERA
Page 371 and 372:
1702 DOES THE CLOCK MAKE THE POISON
Page 373 and 374:
those with high nickel content are
Page 375 and 376:
isk assessment. However, unique cha
Page 377 and 378:
model of APAP metabolism and glutat
Page 379 and 380:
logically & morphologically similar
Page 381 and 382:
posure, blood chemistry was analyze
Page 383 and 384:
elated to oxidative stress by measu
Page 385 and 386:
ostasis), but work is needed to tra
Page 387 and 388:
tokine products during carcinogenes
Page 389 and 390:
ways as chemical stressors and, the
Page 391 and 392:
toxicity of nanomaterials relates s
Page 393 and 394:
1815 MEASURING COMPOUND SELECTIVITY
Page 395 and 396:
1825 EFFECTS OF METABOLISM BY INTES
Page 397 and 398:
cyanoacetic acid increased 2-3 fold
Page 399 and 400:
1845 IS THE PROMISCUITY OF THE ARYL
Page 401 and 402:
crorarray analysis. RT-PCR results
Page 403 and 404:
are a family of phase-II biotransfo
Page 405 and 406:
ous labs. As a result of positive s
Page 407 and 408:
down the doses may produce more tox
Page 409 and 410:
spectively. Below 100 mg/l of gemfi
Page 411 and 412:
1900 GENERATION OF PRECISION CUT LI
Page 413 and 414:
iomarkers or observation of lesions
Page 415 and 416:
creased reticulocytes and lymphocyt
Page 417 and 418:
statistically significant interacti
Page 419 and 420:
monize sample preparation and analy
Page 421 and 422:
NPC and sinonasal cancer in neighbo
Page 423 and 424:
showed incidences of lung and nasal
Page 425 and 426:
utylbenzenes, exhibited most simila
Page 427 and 428:
1975 DIFFERENTIAL MODULATION OF CYP
Page 429 and 430:
organic As to MMA(V) and a lower ca
Page 431 and 432:
ole in invasion and metastasis of c
Page 433 and 434:
3T3-L1 cells to low-levels of arsen
Page 435 and 436:
2011 IDENTIFICATION OF A NOVEL VX M
Page 437 and 438:
This work was supported by Cooperat
Page 439 and 440:
2029 EFFICACY OF ENDOTRACHEAL ADMIN
Page 441 and 442:
Diazepam injections and its combina
Page 443 and 444:
2047 ESTERASE ACTIVITIES AND HEMOST
Page 445 and 446:
nanoparticle-induced toxicity progr
Page 447 and 448:
house, were iv infused into rats ov
Page 449 and 450:
een explored. This study investigat
Page 451 and 452:
croscopic analysis revealed that on
Page 453 and 454:
egg yolk collected from turtles inh
Page 455 and 456:
consistency of results in both expe
Page 457 and 458:
2111 CYTOCHROME P450 3A5 GENOTYPE I
Page 459 and 460:
esidues of organophosphates or thei
Page 461 and 462:
manganism. Recent work from our lab
Page 463 and 464:
Aβ1-40 in CSF and hippocampus in P
Page 465 and 466:
2147 CATALASE MANIPULATIONS MODIFY
Page 467 and 468:
ation based on real-world exposure
Page 469 and 470:
NPs. Aggregation of citrate-stabili
Page 471 and 472:
2175 THE ROLE OF SURFACE CHEMISTRY
Page 473 and 474:
seen rapid uptake in biological ima
Page 475 and 476:
effect on uterine weight or vaginal
Page 477 and 478:
dicating widespread exposure. While
Page 479 and 480:
components into the liver parenchym
Page 481 and 482:
2223 ISOLATION AND DETECTION OF RIC
Page 483 and 484:
stored (-20 celsius degree). The co
Page 485 and 486:
2241 DDA, A BIOMARKER FOR ENVIRONME
Page 487 and 488:
2249 INTERACTION BETWEEN DIETARY SE
Page 489 and 490:
2258 PHARMACOKINETICS, EXCRETION BA
Page 491 and 492:
2267 SENSITIVE AND SPECIFIC FLUORES
Page 493 and 494:
2276 METABOLISM AND DISPOSITION OF
Page 495 and 496:
ment of hypertension in companion a
Page 497 and 498:
for the propyl series can be used f
Page 499 and 500:
2304 IN VITRO EXPOSURE AND EVALUATI
Page 501 and 502:
2313 THE SYNERGISTIC EFFECT OF SODI
Page 503 and 504:
genes that play a crucial role in M
Page 505 and 506:
2330 THE ROLE OF TRANSFORMING GROWT
Page 507 and 508:
ined following up to 96 h continuou
Page 509 and 510:
effect doses obtained with the rat
Page 511 and 512:
diated transcriptional response of
Page 513 and 514:
docrine disruptor activities of EDC
Page 515 and 516:
individuals. Week 6 results were qu
Page 517 and 518:
functionality of photosystem II and
Page 519 and 520:
wild mice (Mus musculus) from areas
Page 521 and 522:
2406 TOXICITY AND BIOACCUMULATION O
Page 523 and 524:
Isocitric acid is the acid in the h
Page 525 and 526:
2425 EFFECTS OF FUMONISINS IN ETHAN
Page 527 and 528:
centration(μg/g) were: 5.1-95.3; 2
Page 529 and 530:
2445 AUTOPHAGY IN DEVELOPMENT: A LI
Page 531 and 532:
sures to inhaled Mn in dust. Nevert
Page 533 and 534:
2466 CRITICAL EVALUATION OF ANIMAL
Page 535 and 536:
elationships predict that resting r
Page 537 and 538:
2489 COMPARATIVE TOXICITY OF BIODIE
Page 539 and 540:
2497 TRANSCRIPTIONAL REGULATION OF
Page 541 and 542:
2506 TOXICOLOGICAL CONSIDERATIONS O
Page 543 and 544:
launched with the aim of developing
Page 545 and 546:
forms mRNA expression levels were a
Page 547 and 548:
2534 CUTANEOUS WOUND HEALING IN THE
Page 549 and 550:
wells (0, 1, 5, 10, 25, 50, 100, an
Page 551 and 552:
2553 AN ORGANOTYPIC MICROLIVER PLAT
Page 553 and 554:
serum-free media. At 24 hrs, the gr
Page 555 and 556:
2572 INCREASED ARSENIC BIOACCESSIBI
Page 557 and 558:
nology to develop improved methods.
Page 559 and 560:
tuna, swordfish, or mako shark (3.5
Page 561 and 562:
nificantly reduce circulating thyro
Page 563 and 564:
grouped into 9 observation periods
Page 565 and 566:
histopathological or biochemical ev
Page 567 and 568:
exhibited a hyperactive phenotype,
Page 569 and 570:
the search of effective drugs for e
Page 571 and 572:
2644 COVALENT BINDING OF 14 C 2-MET
Page 573 and 574:
aries targeting all transcription f
Page 575 and 576:
(p 9 weeks) and CSC phenotype acqui
Page 577 and 578:
2673 IMMUNE-MEDIATED VASCULAR INJUR
Page 579 and 580:
for risk identification and charact
Page 581 and 582:
to control toxicant delivery in tob
Page 583 and 584:
Author Index (Continued) The numera
Page 585 and 586:
Page 587 and 588:
Page 589 and 590:
Page 591 and 592:
Page 593 and 594:
Page 595 and 596:
Page 597 and 598:
Page 599 and 600:
Page 601 and 602:
Page 603 and 604:
Page 605 and 606:
Page 607 and 608:
Page 609 and 610:
Page 611 and 612:
Keyword Index (Continued) Arsenite
Page 613 and 614:
Keyword Index (Continued) Covalent
Page 615 and 616:
Keyword Index (Continued) flow cyto
Page 617 and 618:
Keyword Index (Continued) innate im
Page 619 and 620:
Keyword Index (Continued) nanoparti
Page 621 and 622:
Keyword Index (Continued) preservat
Page 623 and 624:
Keyword Index (Continued) Thrombocy
Page 625 and 626:
Toxicological Sciences The Official
show all

The Toxicologist - Society of Toxicology

Create successful ePaper yourself

Delete template?

Save as template?