The Toxicologist - Society of Toxicology

NPs. Aggregation of citrate-stabilized YVO 4 :Eu NPs occurred at low pH (pH 2)
and under high ionic strength conditions (i.e., PBS, cell culture media). However,
PAA-coated YVO 4 :Eu NPs remain stable without aggregation under these conditions.
Surface coating affected adsorption of soy proteins (used as a simple model
for dietary proteins) to YVO 4 :Eu NPs as evidenced by differences in protein banding
patterns determined by SDS-PAGE. Citrate-stabilized YVO 4 :Eu NPs were
taken up by Caco-2 cells, an intestinal enterocyte model, and detected in the cytoplasm
by fluorescent microscopy. Inductively coupled plasma-optical emissions
spectroscopy indicated uptake of citrate-stabilized YVO 4 :Eu NPs is time- and concentration-dependent.
Both fluorescence microscopy and ICP-OES data suggest
NPs are either removed from or sequestered within the cells following longer exposure
periods (≥ 2 hrs).
2166 INTERNALIZATION OF CARBON BLACK AND IRON
OXIDE NANOPARTICLE MIXTURES LEADS TO
OXIDANT PRODUCTION.
J. Berg and C. M. Sayes. Texas A&M University, Bryan, TX.
Exposure to nanoparticle mixtures is increasing as nanomaterials enter consumer
environments. In this study, the cellular effects of mixed engineered carbon black
(ECB) and iron oxide (Fe2O3) nanoparticles was investigated in order to understand
the mechanism of toxicity and potential methods of mitigation. Lung epithelial
cells (A549) were exposed to mixed Fe2O3 and ECB (± L-ascorbic acid) and
mixed Fe2O3 and surface-oxidized engineered carbon black (ox-ECB). All
nanoparticles were characterized prior to experimentation using a variety of techniques.
Cellular uptake of nanoparticles was analyzed via both fluorescence and
transmission electron microscopy; cellular uptake of iron was quantified using inductively
coupled plasma mass spectrometry. Both the MTT assay and the ethidium
homodimer and calcein AM live/dead assay were used to measure cellular proliferation
and cytotoxicity, respectively. The dichlorofluorescein diacetate assay was
used to measure intracellular reactive oxygen species. Results show that both Fe2O3
and ECB (or ox-ECB) are co-internalized in intracellular vesicles. Additionally,
after exposure to the mixture of nanoparticles, the lysosome (pH TiO2(32nm/anatase-rutile) > CeO2(70nm) >
TiO2(200nm/anatase) = TiO2(10nm/anatase) = TiO2(30nm/anatase-rutile) >
TiO2(25nm/anatase) > TiO2(250nm/rutile)] was detected by LDH release as early
as 24h post-exposure. BEAS2B cellular ROS was induced in differential and dosedependent
manner by all TiO2 NPs [TiO2(25nm/anatase) = TiO2(250nm/rutile)
> TiO2(30nm/anatase-rutile) = TiO2(10nm/anatase) = TiO2(32nm/anatase-rutile)
= TiO2(200nm/anatase) > CeO2(70nm) = CeO2(15nm)]. CeO2 NPs did not induce
ROS in BEAS2B cells at any size or dose. The results demonstrate that differential
toxicity of various TiO2 and CeO2 NPs was detected by in vitro pulmonary
toxicity testing. Metal oxide NP BEAS2B cell cytotoxicity was found not to be dependent
on size alone and did not correlate with the ability to induce ROS. This
abstract does not necessarily reflect EPA policy.
2168 GENE EXPRESSION OF METAL UPTAKE GENES,
USING CDSE/ZNS QUANTUM DOTS IN ZEBRAFISH
LIVER CELLS.
V. Allagadda, S. Tang and G. D. Mayer. The Institute of Environmental & Human
Health, Texas Tech University, Lubbock, TX.
Use of nanoparticles, defined as particles that have at least one dimension of 100
nm or less, is increasing in commercial and medical products. Quantum dots are a
type of fluorescent, semi-conductive nanoparticle that are used in applications from
biological imaging to computer chip manufacture. Increasing use of these types of
particles hastens the need to study their toxicological implications since the toxicological
parameters of quantum dots are not well defined and the toxicological
mechanisms of action are not known. Nanoparticle characteristics differ in size,
surface charge, coating agents and surface chemistries which may influence toxicity
of individual preparations of particles. This study focuses on multiple comparisons
of the toxicities of CdSe quantum dots and cadmium or zinc salts in zebrafish at the
molecular and cellular level. To determine whether particle composition or size
plays an important role in nanocrystal toxicity, zebrafish liver (ZFL) cells were exposed
to various concentrations of quantum dots and cadmium or zinc salts.
Isolated mRNA from these exposures was used to measure the expression of metal
related genes including MT, MTF, DMT, ZIP and ZNT. Gene expression from Cd
or Zn exposures showed that all genes were significantly up regulated in a dose dependant
manner. Three different sizes of CdSe/ZnS QDs were used to expose ZFL
cells at concentrations of 25nM, 50nM and 100nM. CdSe/ZnS nanocrystals altered
gene expression of metal homeostasis genes in a manner different from that of
the corresponding Cd or Zn salts. This implies that toxicity of CdSe nanocrystals is
not due to ionic metal toxicity from particle dissolution.
2169 ACCUMULATION AND TRANSLOCATION OF
NANOMATERIALS ACROSS THE HUMAN PLACENTA.
P. Wick 1 , A. Malek 2 , P. Diener 3 , A. Zisch 2 , H. F. Krug 1 and U. von Mandach 2 .
1 Laboratory for Materials-Biology Interaction, Empa Swiss Federal Laboratories for
Materials Science and Technology, St. Gallen, Switzerland, 2 Department of Obstetrics,
University Hospital Zurich, Zurich, Switzerland and 3 Institute of Pathology,
Kantonsspital St. Gallen, St. Gallen, Switzerland. Sponsor: B. Fadeel.
Background and Objectives: Humans have been exposed to fine and ultrafine particles
throughout their history. Since the Industrial Revolution, sources, doses, and
types of na-noparticles have changed dramatically. In the last decade, the rapidly
developing field of nanotechnology has led to an increase of engineered nanoparticles
with novel physical and chemical properties. Regardless of whether this exposure
is unintended or not, a careful assessment of possible adverse effects is needed.
A large number of projects have been carried out to assess the consequences of combustion-derived
or engineered nanoparticle exposure on human health. In recent
years there has been a growing concern about the possible health influence of exposure
to air pollutants during preg-nancy, hence an implicit concern about potential
risk for nanoparticle exposure in utero. Previous work has not addressed the question
of whether nanoparticles may cross the placenta.
Methods: We used the ex vivo human placental perfusion model to investigate
whether nanoparticles can cross this barrier and whether this process is size dependent.
Fluores-cently labeled polystyrene beads with diameters of 50, 80, 240, and
500 nm were chosen as model particles.
Results: We showed that fluorescent polystyrene particles with diameter up to 240
nm were taken up by the placenta and were able to cross the placental barrier without
affect-ing the viability of the placental explant.
Conclusions: The findings suggest that nanomaterials have the potential for
transplacental transfer and underscore the need for further nanotoxicologic studies
on this important organ system.
2170 CYTOTOXICITY AND BIOKINETICS OF POLYMERIC
MAGHEMITE NANOPARTICLES IN VITRO.
V. Sorribas 1 , L. Mohamed-Ahmed-Ali 2, 1 , R. Villa-Bellosta 1 , A. Millan 1 , L.
Gabilondo 2 , R. Piñol 2 and F. Palacio 2 . 1 Laboratory of Molecular Toxicology,
University of Zaragoza, Zaragoza, Spain and 2 Insitute of Materials Science, CSIC,
Zaragoza, Spain. Sponsor: A. Anadon.
Biocompatible ferrofluids are stable suspensions of superparamagnetic nanoparticles
(NP) that can be used in several medical applications, such as diagnosis, MRI
contrast agents, targetted drug delivery, and as magnetothermic tools that respond
SOT 2011 ANNUAL MEETING 465