Identification of deregulated genes by single wall carbon-nanotubes in
human normal bronchial epithelial cells
Anas Alazzam, PhD
a,b
, Etienne Mfoumou, PhD
a,b
, Ion Stiharu, PhD
a
, Amal Kassab, BSc
a
,
Andrew Darnel, PhD
b
, Amber Yasmeen, PhD
b
, Narayanswamy Sivakumar, PhD
a
,
Rama Bhat, PhD
a
, Ala-Eddin Al Moustafa, PhD
a,b,c,
⁎
a
Department of Mechanical and Industrial Engineering Concordia University, Montréal, Quebec, Canada
b
Segal Cancer Centre, Lady Davis Institute for Medical Research of the Sir Mortimer B. Davis-Jewish General Hospital, McGill University, Montréal, Canada
c
Syrian Research Cancer Centre of the Syrian Society against Cancer and Department of Anatomy & Embryology of the Aleppo University, Aleppo, Syria
Received 12 May 2009; accepted 7 December 2009
Abstract
To identify genes affected by single-walled carbon nanotubes (SWCNTs) in human normal lung cells, we compared the gene expression
profiles of untreated human normal bronchial epithelial (HNBE) cells to profiles of HNBE cells treated with SWCNTs. A complementary
DNA microarray analysis consisting of 54,675 human genes revealed marked changes in the expression of 14,294 genes, with 7,029 genes
being upregulated and 7,265 being downregulated. This comprehensive list of genes included those associated with cell cycle, apoptosis,
cell survival, cell adhesion and motility, signal transduction, and transcription regulation. Additional analysis of 19 genes using reverse
transcription–polymerase chain reaction confirmed the microarray analysis. More specifically, our study demonstrates to our knowledge for
the first time, evidence that 9 of the 19 genes (most of which encode cell apoptotic, signal transduction, and transcription regulator
products) are upregulated in the SWCNTs-treated HNBE cells as compared with untreated cells, whereas the remaining 10 of the 19
(involved in cell adhesion and motility, cell proliferation, and cell survival) are downregulated in SWCNTs-treated HNBE cells in
comparison with untreated controls. These findings provide a large body of information regarding gene expression profiles associated with
SWCNTs exposure in human lung bronchial epithelial cells, and also represent a source to investigate the mechanism of the effect of
SWCNTs in human normal lung cells.
From the Clinical Editor: In this study, the gene expression profile of human normal bronchial epithelial cells was compared with single-
wall carbon nanotubes-treated cells. A cDNA microarray analysis consisting of 54,675 human genes revealed significant changes in the
expression of 14,294 genes, with 7,029 genes being up-regulated and 7,265 being down-regulated. This serves as a first step in clarification
of mechanisms of action and to investigate toxicity in this model.
© 2010 Elsevier Inc. All rights reserved.
Key words: Single-walled carbon nanotubes; Human bronchial epithelial cells; Complementary DNA microarray; Gene expression
Carbon nanotubes (CNTs) offer exciting opportunities for
science and applications. In recent years CNTs research has
become established as a highly interdisciplinary field to exploit
their outstanding features.
1
Conceptually, single-walled carbon
nanotubes (SWCNTs) are considered as small strips of graphene
sheets that have been rolled up to form perfect seamless single-
walled nanocylinders. CNTs have the added advantage of being
potential nanofluidic devices for controlled drug delivery.
1,2
Great interest has been generated in fullerenes in general, but
especially in CNTs and carbon nanohorns as biologically
compatible materials and drug carriers mainly because of their
distinct architecture, hollow interior, and cagelike structures.
However, the small size, large surface area, and high reactivity of
these materials are the main factors for potential toxicity.
3
Moreover, CNTs will have widespread applications in many
technological fields; thus, worker-consumer exposure is likely to
occur, posing emerging health concerns.
3,4
Initial toxicological
studies demonstrated that pulmonary deposition of SWCNTs or
multiwalled carbon nanotubes causes acute pulmonary
BASIC SCIENCE
Nanomedicine: Nanotechnology, Biology, and Medicine 6 (2010) 563 – 569
Original Article
www.nanomedjournal.com
This research is supported by Concordia University, the Canadian
Institutes for Health Research (CIHR), and the Fonds de la Recherche en
Santé du Québec (FRSQ-Réseau du Cancer).
⁎
Corresponding author: Segal Cancer Centre, Lady Davis Institute for
Medical Research of the SMBD-Jewish General Hospital, Montréal, Quebec,
Canada H3T 1E2.
E-mail addresses: ala-eddin.almoustafa@mcgill.ca,
aalmoust@encs.concordia.ca (A.-E. Al Moustafa).
1549-9634/$ – see front matter © 2010 Elsevier Inc. All rights reserved.
doi:10.1016/j.nano.2009.12.005
Please cite this article as: A., Alazzam, et al, Identification of deregulated genes by single wall carbon-nanotubes in human normal bronchial epithelial cells.
Nanomedicine: NBM 2010;6:563-569, doi:10.1016/j.nano.2009.12.005