4 research outputs found
Chronic Exposure to Carbon Nanotubes Induces Invasion of Human Mesothelial Cells through Matrix Metalloproteinase‑2
Malignant mesothelioma is one of the most aggressive forms of cancer known. Recent studies have shown that carbon nanotubes (CNTs) are biopersistent and induce mesothelioma in animals, but the underlying mechanisms are not known. Here, we investigate the effect of long-term exposure to high aspect ratio CNTs on the aggressive behaviors of human pleural mesothelial cells, the primary cellular target of human lung mesothelioma. We show that chronic exposure (4 months) to single- and multiwalled CNTs induced proliferation, migration, and invasion of the cells similar to that observed in asbestos-exposed cells. An up-regulation of several key genes known to be important in cell invasion, notably matrix metalloproteinase-2 (MMP-2), was observed in the exposed mesothelial cells as determined by real-time PCR. Western blot and enzyme activity assays confirmed the increased expression and activity of MMP-2. Whole genome microarray analysis further indicated the importance of MMP-2 in the invasion gene signaling network of the exposed cells. Knockdown of MMP-2 in CNT and asbestos-exposed cells by shRNA-mediated gene silencing effectively inhibited the aggressive phenotypes. This study demonstrates CNT-induced cell invasion and indicates the role of MMP-2 in the process
Early Assessment and Correlations of Nanoclay’s Toxicity to Their Physical and Chemical Properties
Nanoclays’ functionalization
with organic modifiers increases
their individual barrier properties, thermal stability, and mechanical
properties and allows for ease of implementation in food packaging
materials or medical devices. Previous reports have shown that, while
organic modifiers integration between the layered mineral silicates
leads to nanoclays with different degrees of hydrophobicity that become
easily miscible in polymers, they could also pose possible effects
at inhalation or ingestion routes of exposure. Through a systematic
analysis of three organically modified and one pristine nanoclay,
we aimed to relate for the first time the physical and chemical characteristics,
determined via microscopical and spectroscopical techniques, with
the potential of these nanoclays to induce deleterious effects in
in vitro cellular systems, i.e. in immortalized and primary human lung
epithelial cell lines. To derive information on how functionalization
could lead to toxicological profiles throughout nanoclays’
life cycle, both as-received and thermally degraded nanoclays were
evaluated. Our analysis showed that the organic modifiers chemical
composition influenced both the physical and chemical characteristics
of the nanoclays as well as their toxicity. Overall, when cells were exposed to nanoclays with
organic modifiers containing bioreactive groups, they displayed lower cellular
numbers as well more elongated cellular morphologies relative to the
pristine nanoclay and the nanoclay containing a modifier with long carbon
chains. Additionally, thermal degradation caused loss of the organic
modifiers as well as changes in size and shape of the nanoclays, which
led to changes in toxicity upon exposure to our model cellular systems. Our study provides insight into the synergistic
effects of chemical composition, size, and shape of the nanoclays
and their toxicological profiles in conditions that mimic exposure
in manufacturing and disposal environments, respectively, and can
help aid in safe-by-design manufacturing of nanoclays with user-controlled
functionalization and lower toxicity levels when food packaging applications
are considered
Short-Term Pulmonary Toxicity Assessment of Pre- and Post-incinerated Organomodified Nanoclay in Mice
Organomodified nanoclays
(ONCs) are increasingly used as filler
materials to improve nanocomposite strength, wettability, flammability,
and durability. However, pulmonary risks associated with exposure
along their chemical lifecycle are unknown. This study’s objective
was to compare pre- and post-incinerated forms of uncoated and organomodified
nanoclays for potential pulmonary inflammation, toxicity, and systemic
blood response. Mice were exposed <i>via</i> aspiration
to low (30 μg) and high (300 μg) doses of preincinerated
uncoated montmorillonite nanoclay (CloisNa), ONC (Clois30B), their
respective incinerated forms (I-CloisNa and I-Clois30B), and crystalline
silica (CS). Lung and blood tissues were collected at days 1, 7, and
28 to compare toxicity and inflammation indices. Well-dispersed CloisNa
caused a robust inflammatory response characterized by neutrophils,
macrophages, and particle-laden granulomas. Alternatively, Clois30B,
I-Clois30B, and CS high-dose exposures elicited a low grade, persistent
inflammatory response. High-dose Clois30B exposure exhibited moderate
increases in lung damage markers and a delayed macrophage recruitment
cytokine signature peaking at day 7 followed by a fibrotic tissue
signature at day 28, similar to CloisNa. I-CloisNa exhibited acute,
transient inflammation with quick recovery. Conversely, high-dose
I-Clois30B caused a weak initial inflammatory signal but showed comparable
pro-inflammatory signaling to CS at day 28. The data demonstrate that
ONC pulmonary toxicity and inflammatory potential relies on coating
presence and incineration status in that coated and incinerated nanoclay
exhibited less inflammation and granuloma formation than pristine
montmorillonite. High doses of both pre- and post-incinerated ONC,
with different surface morphologies, may harbor potential pulmonary
health hazards over long-term occupational exposures
Short-Term Pulmonary Toxicity Assessment of Pre- and Post-incinerated Organomodified Nanoclay in Mice
Organomodified nanoclays
(ONCs) are increasingly used as filler
materials to improve nanocomposite strength, wettability, flammability,
and durability. However, pulmonary risks associated with exposure
along their chemical lifecycle are unknown. This study’s objective
was to compare pre- and post-incinerated forms of uncoated and organomodified
nanoclays for potential pulmonary inflammation, toxicity, and systemic
blood response. Mice were exposed <i>via</i> aspiration
to low (30 μg) and high (300 μg) doses of preincinerated
uncoated montmorillonite nanoclay (CloisNa), ONC (Clois30B), their
respective incinerated forms (I-CloisNa and I-Clois30B), and crystalline
silica (CS). Lung and blood tissues were collected at days 1, 7, and
28 to compare toxicity and inflammation indices. Well-dispersed CloisNa
caused a robust inflammatory response characterized by neutrophils,
macrophages, and particle-laden granulomas. Alternatively, Clois30B,
I-Clois30B, and CS high-dose exposures elicited a low grade, persistent
inflammatory response. High-dose Clois30B exposure exhibited moderate
increases in lung damage markers and a delayed macrophage recruitment
cytokine signature peaking at day 7 followed by a fibrotic tissue
signature at day 28, similar to CloisNa. I-CloisNa exhibited acute,
transient inflammation with quick recovery. Conversely, high-dose
I-Clois30B caused a weak initial inflammatory signal but showed comparable
pro-inflammatory signaling to CS at day 28. The data demonstrate that
ONC pulmonary toxicity and inflammatory potential relies on coating
presence and incineration status in that coated and incinerated nanoclay
exhibited less inflammation and granuloma formation than pristine
montmorillonite. High doses of both pre- and post-incinerated ONC,
with different surface morphologies, may harbor potential pulmonary
health hazards over long-term occupational exposures