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Journal of Clinical and Experimental Toxicology | Volume: 03 | ISSN: 2630-4570
allied
academies
November 04-05, 2019 | Prague, Czech Republic
2
nd
World Congress on
TOXICOLOGY AND APPLIED PHARMACOLOGY
Long-Fibre carbon nanotubes induce Sporadic Pleural Mesothelioma recapitulating
Human Disease: A role for epigenetic mechanisms in disease development
Joaquin Zacarias-Cabeza
University of Cambridge, UK
E
xposure to asbestos fibres causes pathological changes
in the pleural cavity, including malignant mesothelioma.
Length-dependent retention of asbestos fibres in the
pleural cavity is crucial for disease development. Chronic
inflammation induced by biopersistent pathogenic asbestos
fibres plays a key role in carcinogenesis. Use of manufacture
carbon nanotubes (CNT) is growing which increases
occupational exposures of these materials. Manufactured
carbon nanotubes (CNT) are similar to asbestos in terms of
their high aspect-ratio and thus may pose an asbestos-like
inhalation hazard; however, the molecular mechanisms
underlying CNT toxicity and carcinogenic potential have not
been sufficiently explored. Epigenetics is one area of interest
that has been quickly developing to assess disease processes
due to its ability to change gene expression and thus the
lung environment after exposure. Using a mouse model of
direct injection of long asbestos fibres and long-CNT into
the pleural cavity, we compared the molecular changes in
the mesothelium induced by these fibres over prolonged
exposure times following injection.
We show a common molecular signature in the molecular
changes induced by long-CNT and long asbestos throughout
disease progression leading to the development of sporadic
malignant mesothelioma. Our transcriptome analysis
shows that gene expression profiles are similarly altered in
the presence of long-CNT and long asbestos, compared to
control mice at matched exposure times. Epigenetic changes
induced by pathogenic fibres (long-CNT and asbestos)
occur at the pre-neoplastic stage of disease and may play
a key role in progression of pleural inflammatory lesions to
malignant mesothelioma. Together, these data demonstrate
that exposure to long-CNT induces development of sporadic
pleural mesothelioma replicating the pathogenesis of human
disease and highlights commonality in the hazard mechanism
of long pathogenic fibres at the molecular level. Crucially,
our findings reinforce concerns that high aspect-ratio CNT
may pose an asbestos-like hazard, leading to malignant
mesothelioma.
e:
jzc22@mrc-tox.cam.ac.ukJ Clin Exp Tox, Volume: 03
DOI: 10.35841/2630-4570-C2-009
Notes: