The Toxicologist - Society of Toxicology

More documents

Recommendations

Info

the DFP dose was 1.7 mg/kg, improvements were noted with gait (p = 0.042), activity (p = 0.078), and posture (p = 0.059), with involuntary movements and gait score differences between DFP-treated and DFP + fullerene-treated mice at p = 0.12 and p = 0.20, respectively, 5-30 min after ip dosing. With further development, these initial experiments suggest that fullerenes have potential for use against toxicities induced by OP compounds. Supported by NIH 1U01NS063723. 2577 PROLINE RICH POLYPEPTIDES MITIGATE THE EFFECTS OF WHOLE-BODY IRRADIATION IN MICE. K. D. Thrall 1 , M. Franch 2 , J. E. Morris 1 and R. E. Weller 1 . 1 Battelle, Pacific Northwest Division, Richland, WA and 2 North Carolina State University, Raleigh, NC. The development of medical countermeasures to mitigate or prevent the effects of ionizing radiation is of great importance. Proline rich polypeptides (PRPs) are small chains of amino acids that regulate the production of cytokines and immune functions in the body, and may repair bone marrow cells damaged by high doses of ionizing radiation. A study was conducted to evaluate the efficacy of PRP to restore hematopoietic stem cells and increase the survival of lethally irradiated male Swiss- Webster mice. Proline rich polypeptide was administered to mice as either a single or repeated dose at a high (20 μg) or low (2 μg) level by intraperitoneal injection pre-, post-, or pre- and post- X-ray irradiation at 6.5 and 7.0 Gy. Hematological parameters measured at interim sacrifices (5 and 12 days post irradiation) showed no statistical increased over animals treated with PRP compared to controls, although 30-day recovery was much greater in treated animals. Over 30 days, animals receiving repeated administration of PRP showed a significant increase in survivability (80%) compared to control animals and animals treated with single doses of material (47%). Importantly, time to mortality was increased by 5-7 days in treated groups. 2578 PROTECTIVE ROLE OF DEFEROXAMINE ON BEHAVIORAL EFFECTS IN TRANSGENIC (TG-2576) MICE EXPOSED TO A HIGH ALUMINUM DOSE. M. Gómez, J. L. Domingo, T. Garcia, D. Ribes and M. Colomina. Toxicology and Environmental Health, Universitat Rovira i Virgili, Reus, Spain. Aluminum (Al), the most abundant metal in the earth crust, is not an essential element. However, it is well established that Al is potentially neurotoxic, being Al exposure linked to some serious neurological disorders including Alzheimer’s disease (AD). Biometal deregulations, metal interactions with Abeta, as well as metal-mediated oxidative stress have been implicated in the etiology of AD. The effectiveness of metal chelators has been investigated as a possible therapy in AD treatment. It is well known that deferoxamine (DFO), a hexadentate trihidroxamic acid, acts as an effective Al chelator. However, nowadays there are no data showing whether DFO can improve the behavioral alterations caused by Al exposure in mammals. In recent years, the use of a transgenic mouse model of AD (Tg-2576) has improved the sensitivity of experimental approaches to the potential relationship between Al and AD. The aim of the present study was to assess in 5-months old Tg2576 mice exposed to a chronic oral dose of aluminum lactate (given through the diet, 1 mg Al/g for 6 months) the effects on learning and memory using a Morris Water Maze task. Wild mice were used as controls. General motor activity and anxiety levels were also evaluated using an open-field test. The Water Maze test consisted of 5 acquisition days (4 trials per day) and a probe test at the end of the last acquisition day. The open-field test showed an increased ratio (total distance traveled in the center/total distance traveled) in DFO-treated animals, indicating an anxyolitic effect of DFO, affecting mainly to wild mice. However, no significant Al effects on general motor activity were found. The Water Maze test did not show DFO effects on learning and memory in Al-treated mice. Significant interactions between genotype and DFO indicate the importance of genotype in evaluating neurotoxic effects of metals and chelating agents. 2579 ARE THE NEUROTOXIC EFFECTS OF MANGANESE DUE TO BLOCKAGE OF POST-SYNAPTIC DOPAMINE RECEPTORS. M. Nelson, T. Adams, D. Beaubrun, M. A. Carroll and E. J. Catapane. Biology, Medgar Evers College, Brooklyn, NY. Manganese (Mn) causes Manganism by disrupting dopaminergic neurotransmission, but the mechanism is unclear. p-Aminosalicylic acid (PAS) is reported an effective treatment but its mechanism is unclear. Lateral cilia of gill of Crassostrea virginica are controlled by serotonergic-dopaminergic nerves from their ganglia. Dopamine (DA) produces cilio-inhibition, serotonin (HT) cilio-excitation. 552 SOT 2011 ANNUAL MEETING Previous work showed Mn blocks cilio-inhibition of DA and is prevented by PAS. We now studied if Mn is blocking DA post-synaptic receptor binding and if PAS prevents Mn from doing this. We observed membrane potentials of lateral ciliated cells using DIBAC, a voltage sensitive fluorescent dye, while measuring cilia beating rates. Applying HT to gill or 5 Hz electrical stimulation (ES) to the branchial nerve caused prolonged membrane depolarization and increased cilia beating rates. Applying DA or 20 Hz ES after exciting cilia repolarized the cell and decreased beating rates. Mn prevented the cilio-inhibition and repolarization. This was prevented when gills were co-treated with PAS. Adding ATP to gill increased cilia beating rates without changing membrane potential. Applying MDL, an adenylcyclase inhibitor, after Mn decreased beating rates without affecting membrane potential. The study shows a correlation between membrane potential of lateral cells and cilia beating rates. It also helps elucidate the neurotoxic mechanism of action of Mn by showing the site of action is after the post-synaptic DA receptors because MDL slowed down cilia in the presence of Mn. This information is helpful to understand causes and potential therapeutic treatments of Manganism. This work was supported by 2R25GM06003 of the Bridge Program of NIGMS, 0516041071 of NYSDOE and 0622197 of the DUE Program of NSF. 2580 THE ABILITY OF PAS, ACETYLSALICYLIC ACID, AND CALCIUM EDTA TO PROTECT AGAINST THE TOXIC EFFECTS OF MANGANESE ON MITOCHONDRIAL RESPIRATION AND MEMBRANE POTENTIAL IN THE GILL OF CRASSOSTREA VIRGINICA. C. Saddler, L. Duncanson, J. Joseph, S. Crawford, E. J. Catapane and M. A. Carroll. Biology, Medgar Evers College, Brooklyn, NY. Manganese (Mn) is an essential metal that at excessive levels in brain causes Manganism, which is similar to Parkinsons disease. The mechanism of action is not completely understood but may be due to mitochondrial damage and resulting dysfunction of the brain’s dopaminergic system. Previously, we showed lateral cilia of gill of Crassostrea virginica are controlled by serotonergic-dopaminergic innervations from their ganglia and Mn treatments disrupts the cilio-inhibitory dopaminergic system. Here we studied effects of Mn on mitochondrial respiration and membrane potential. We prepared mitochondria from gill and studied respiration and mitochondrial membrane potential using the cationic dye TMRM (Tetramethylrhodamine, methyl ester, perchlorate). We also took time lapse micrographs of gill filaments and mitochondrial smears treated with TMRM. Mn caused dose dependent decreases in O 2 consumption, which was blocked by pretreating with calcium disodium EDTA (caEDTA), p-aminosalicylic acid (PAS) or acetylsalicylic acid (ASA). Each partially reversed the toxic effects of Mn when added to Mn treated mitochondria. Mn decreased mitochondrial membrane potentials and was partially blocked by PAS, but not caEDTA. Time lapse photography revealed the fluorescence of specimens treated with Mn dimmed over a 10 minute period indicating a loss of mitochondrial membrane potential. Pretreatment with PAS or ASA prevented the dimming. The study demonstrates that Mn reduces oxygen consumption and disrupts the mitochondrial membrane potential. PAS and ASA protected against both toxic effects and may be a better therapeutic agents than caEDTA in the treatment of Manganism. This work was supported by 2R25GM06003 of the Bridge Program of NIGMS, 0516041071 of NYSDOE and 0622197 of the DUE Program of NSF. 2581 INTERNATIONAL WORKSHOP ON ALTERNATIVE METHODS TO REDUCE, REFINE, AND REPLACE THE USE OF ANIMALS IN VACCINE POTENCY AND SAFETY TESTING. J. Kulpa-Eddy 1 , R. McFarland 2 , R. Isbrucker 3 , M. Halder 4 , H. Kojima 5 , B. Jones 6 , N. Johnson 6 , D. Allen 6 , E. Lipscomb 6 , S. Morefield 6 , W. Casey 7 and W. Stokes 7 . 1 USDA, Riverdale, MD, 2 U.S. FDA, Rockville, MD, 3 Health Canada, Ottawa, ON, Canada, 4 ECVAM, Ispra, Italy, 5 JaCVAM, Tokyo, Japan, 6 ILS, Inc., Research Triangle Park, NC and 7 NICEATM, NIEHS, Research Triangle Park, NC . Vaccines represent a vital tool in the prevention of infectious diseases. However, regulatory testing to meet vaccine lot release requirements can involve large numbers of animals that may experience unrelieved pain and distress. To advance scientifically sound alternative methods that reduce, refine and replace animal use for human and veterinary vaccine potency and safety testing, NICEATM/ICCVAM organized an international workshop in partnership with ECVAM, JaCVAM and Health Canada. Nearly 200 scientists from 13 countries participated in this SOT co-sponsored workshop. Workshop participants identified knowledge and data gaps that need to be addressed to develop alternative methods. They also identified and prioritized research, development and validation activities needed to address these knowledge and data gaps, including the application of new science and tech-
nology to develop improved methods. They agreed that vaccines that use the largest number of animals and that are associated with the greatest pain and distress should be the highest priority for development and validation of alternative methods. High priorities included implementation and further optimization/development activities for alternative methods for rabies and Clostridial vaccines. Participants also emphasized the need to find ways to avoid or minimize challenge testing with live viruses and bacteria that are hazards to laboratory workers or the environment. Ways to promote the increased use of accepted methods were also discussed. Implementation of the workshop recommendations is expected to advance the use and availability of alternative methods for vaccine potency and safety testing while ensuring continued protection of human and animal health. ILS Staff supported by NIEHS contract N01-ES-35504. 2582 ENERGY BALANCE IN MICE CONSUMING A HIGH FAT DIET AND WHEY PROTEIN. H. G. Shertzer 1 , S. E. Woods 1 , M. Krishan 1 ,M. Genter 1 and K. J. Pearson 2 . 1 Environmental Health, University of Cincinnati Medical Center, Cincinnati, OH and 2 Graduate Center for Nutritional Sciences, University of Kentucky, Lexington, KY. In mice and humans, a high fat (HF) diet results in excessive weight gain, adiposity and secondary metabolic complications associated with increased risk for fatty liver disease and type 2 diabetes. Protein rich diets may improve various aspects of HF diet-mediated metabolic disorders. The objective of this study was to evaluate the influence of whey protein isolate (WPI) on metabolic changes in mice fed a HF diet, in the context of systemic energy balance. C57BL/6J mice received either a normal diet or a HF diet for 11 weeks. A subgroup of mice consuming HF diet was administered 0.1 g WPI/ml drinking water. WPI diminished the HF diet-induced increases in body weight and percent body fat, although caloric consumption was constant in all groups. These results could be explained by the finding that HF diet decreased basal metabolic rate, respiratory quotient, and hepatic mitochondrial respiration, effects prevented by WPI. Furthermore, WPI restored the diminished intake of protein that occurs with the HF diet, and reduced fat and carbohydrate consumption commensurate with the increase in protein. Health implications for WPI in association with a HF diet were reflected in early biomarkers for fatty liver disease and type 2 diabetes. We found that WPI diminished HF diet-associated fatty liver, by reducing the number of hepatic lipid droplets and deposition of nonpolar lipids by 43% and 76%, respectively. Furthermore, WPI improved glucose tolerance and prevented the increase in insulin resistance in mice fed the HF diet. We conclude that in mice receiving a HF diet, consumption of WPI increases basal metabolic rate and blocks the metabolism of dietary lipid. Since WPI ameliorates the deleterious effects of HF diet-mediated hepatosteatosis and insulin resistance, WPI dietary supplements may intervene in the early stages of developing fatty liver disease and type 2 diabetes. (NIEHS Center for Environmental Genetics P30 ES06096) 2583 A COMPARATIVE STUDY OF NICOTINAMIDE AND TAURINE FOR ANTI-DIABETIC AND ANTIOXIDANT ACTIONS IN STREPTOZOTOCIN-INDUCED DIABETES IN RATS. K. G. Pandya and C. A. Lau-Cam. St. John’s University, Jamaica, NY. Nicotinamide (NIC) and taurine (TAU) are two natural compounds possessing biological properties relevant to diabetes mellitus (DM). While NIC has shown potential for preventing the development of DM, TAU has demonstrated insulin-like effects and antioxidant and hypolipidemic actions. On these premises, the present study was designed to compare NIC and TAU for the ability to protect against typical DM-induced biochemical alterations in an animal model. For this purpose, Sprague Dawley rats (225-250 g) were treated with an oral dose of either NIC or TAU (2.4 mM/kg in citrate buffer pH 4.5), followed 45 min later by an intraperitoneal dose of streptozotocin (STZ) (60 mg/kg in citrate buffer pH 4.5). Treatments with NIC or TAU were continued after 1 day and for another 54 days. Control animals received only citrate buffer pH 4.5 each day. On day 57 of the study, the animals were decapitated to obtain blood samples, which were processed for plasma, and the plasma fractions analyzed for glucose, insulin, cholesterol, triglycerides, malondialdehyde, nitric oxide, reduced glutathione, glutathione disulfide, catalase, glutathione peroxidase and superoxide dismutase. STZ-induced DM resulted in marked increases (ranging from 64-330% over control values) in all parameters but reduced glutathione and antioxidant enzyme activities, which were reduced (by 49-65% of control values). A pretreatment and post treatment with either NIC or TAU led to a significant attenuation of the altering effects of DM, with potency differences between these two compounds not exceeding 10% of each other. The only exceptions were the effects on plasma lipids, for which NIC was inactive, and the plasma NO, for which TAU was more potent than NIC. The present results indicate that while NIC and TAU can provide equipotent protection against the development of DM and its biochemical consequences, NIC is less appropriate because of a lack of hypolipidemic effect and a weaker action on NO depletion. 2584 COMPARISON OF THE EFFECTS OF NICOTINAMIDE AND TAURINE IN THE BRAIN AND SPINAL CORD AGAINST OXIDATIVE STRESS BY STREPTOZOTOCIN- INDUCED DIABETES IN RATS. S. N. Patel and C. A. Lau-Cam. St. John’s University, Jamaica, NY. Diabetes fosters a state of oxidative stress manifested by lipid peroxidation, free radical production and the loss of antioxidant defenses. Nicotinamide (NIC) and taurine (TAU) are two natural compounds which, in this laboratory, have shown the ability to attenuate oxidative stress in the central nervous system of rats when acutely administered before a diabetogen such as streptozotocin (STZ). The present study was undertaken to specifically determine the effect of a long term treatment with either NIC or TAU on diabetes-induced oxidative stress in the brain and spinal cord and the extent of such an effect in various brain areas. In the study, Sprague-Dawley rats (225-250 g) were treated with an oral dose of NIC or TAU (2.4 mM/kg) in citrate buffer pH 4.5, followed 45 min later by an intraperitoneal dose of STZ (60 mg/kg in citrate buffer pH 4.5). A treatment with NIC, TAU or NIC + TAU was continued for an additional 54 days. During this time, control animals received only citrate buffer pH 4.5 each day. On day 57, the brains were removed following decapitation and sectioned into portions representing the brain stem, cerebellum, cortex and spinal cord. An aliquot of each brain area was homogenized with PBS pH 7.4 (1:30, w/v) and the supernatant isolated upon centrifugation was used to assay malondialdehyde (MDA), nitric oxide (NO), reduced (GSH) and oxidized (GSSG) glutathione, and the antioxidant enzymes catalase (CAT), glutathione peroxidase (GPX) and superoxide dismutase (SOD). Relative to control samples, diabetes induced MDA formation, which was significant only in the spinal cord and cerebellum, and increased NO and GSSG while lowering the GSH, GSH/GSSG ratio, and activities of antioxidant enzymes in all brain areas. Generally, the cortex was the most affected and the brain stem the least. Although TAU and NIC attenuated the actions of STZ-induced oxidative stress throughout, at the present doses NIC was usually more potent than TAU, especially against changes in the values of NO, GPX and SOD. 2585 PROTECTIVE EFFICACY OF A COMBINATION OF HUPERZINE A STEREOISOMERS AGAINST SOMAN EXPOSURE IN GUINEA PIGS. Y. Wang 1 , Y. Wei 1 , S. Oguntayo 1 , N. Jensen 2 and M. P. Nambiar 1, 3 . 1 Closed Head Injury, Walter Reed Army Institute of Research, Silver Spring, MD, 2 Collaborative Research Facility, U.S. Army Medical Research Institute of Chemical Defense, Edgewood, MD and 3 Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD. The mechanism of neuropathology after lethal exposure to nerve agents is complex. Optimal neuroprotection requires drugs with multiple properties to protect against seizures, neuronal degeneration and inflammation as well as induction of neuroregeneration. Huperzine A (Hup), a potential Alzheimer’s disease drug, has several beneficial effects including modification of beta-amyloid peptide, reduction of oxidative stress, anti-inflammation, anti-apoptosis and regulation of nerve growth factor. Natural [-]-Hup is a reversible AChE inhibitor that restricts its neuroporotective ability for treatment. [+]-Hup A, a stereoisomer, is a poor AChE inhibitor and can be used as both pre-/post-exposure treatments. We proposed that particular combination of [-]-Hup or [+]-Hup, with different degrees of AChE inhibition can protect strongly by both the mechanisms of reversible AChE inhibition and neuroprotection against nerve agents. Efficacy of [+]-Hup and [+]&[-]-Hup was evaluated in a guinea pig model. Animals were pretreated with [+]-Hup (40mg/kg) or pyridostigmine bromide (PB, 26μg/kg, im) and 30 min later exposed to 1.2 X LD50 soman (GD, 33.6μg/kg, sc), and a combination of atropine (2 mg/kg, im) and 2-PAM (25mg/kg, im) 1 min after GD exposure. EEG and ECG were recorded for 24 h. The survival rate for PB group, [+]-Hup group and [+]&[-]-Hup group was 30%, 80% and 100% (n=10) respectively. Compared to PB, pretreatment with [+]&[-]-Hup and [+]-Hup significantly inhibited epileptic EEG powers (n=8, p
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 and 298:
third tetratricopeptide repeats (TP
Page 299 and 300:
7d. 28d after TMT injury there was
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: 2572 INCREASED ARSENIC BIOACCESSIBI
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 607 and 608:
Author Index (Continued) The numera
Page 609 and 610:
Author Index (Continued) The numera
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

You also want an ePaper? Increase the reach of your titles

Delete template?

Save as template?