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Effect of nanoparticles on human cells from healthy individuals and patients with respiratory diseases.

Ever increasing applications of nanomaterials (materials with one or more dimension
less than 100 nm) has raised awareness of their potential genotoxicity. They have
unique physico¿chemical properties and so could have unpredictable effects. Zinc oxide
(ZnO) and titanium dioxide (TiO2) are widely used in a number of commercial
products. There are published studies indicating that some forms of these compounds
may be photo-clastogenic in mammalian cells. What has not been investigated before is
the effect of nanoparticles from these compounds in human germ cells. Thus the
present study has examined their effects in the presence and absence of UV light in
human sperm and compared responses to those obtained with human lymphocytes using
the Comet assay to measure DNA damage. The effect of nanoparticles (40-70nm range)
was studied in human sperm and lymphocytes in the dark, after pre-irradiation with UV
and simultaneous irradiation with UV. The studies do provide some evidence that there
are photo-genotoxic events in sperm and lymphocytes in the absence of overt toxicity.
The cytotoxic and genotoxic potentials of ZnO and TiO2 as well as their effect on
phosphotyrosine expression, were examined in the human epithelial cervical carcinoma
cells (Hela cells). This was done to try and determine the underlying molecular events
resulting from their exposure to ZnO and TiO2 nanoparticles occurring at the same time
as DNA is damaged. Concentration- and time-dependent cytotoxicity, and an increase
in DNA and cytogenetic damage with increasing nanoparticle concentrations were
reported in this study. Mainly for zinc oxide, genotoxicity was clearly associated with
an increase in tyrosine phosphorylation.
Nanotechnology has raced ahead of nanotoxicology and little is known of the effects of
nanoparticles in human systems, let alone in diseased individuals. Therefore, the effects
of TiO2 nanoparticles in peripheral blood lymphocytes from patients with respiratory
diseases (lung cancer, chronic obstructive pulmonary disease (COPD) and asthma) were
compared with those in healthy individuals using genotoxic endpoints to determine
whether there are any differences in sensitivity to nano-chemical insult between the
patient and control groups. The results have shown concentration dependent genotoxic
effects of TiO2 in both respiratory patient and control groups in the Comet assay and an
increasing pattern of cytogenetic damage measured in the micronucleus assay without
being statistically significant except when compared with the untreated controls of
healthy individuals. Furthermore, modulation of ras p21 expression was investigated.
Regardless of TiO2 treatment, only lung cancer and COPD patients expressed
measurable ras p21 levels that showed modulation as the result of nanoparticle
treatment.
Results have suggested that both ZnO and TiO2 nanoparticles can be genotoxic over a
range of concentrations without either photoa-ctivation or being cytotoxic.

Identiferoai:union.ndltd.org:BRADFORD/oai:bradscholars.brad.ac.uk:10454/4864
Date January 2010
CreatorsOsman, Ilham F.
ContributorsAnderson, Diana, Thorning, Paul
PublisherUniversity of Bradford, Biomedical Sciences
Source SetsBradford Scholars
LanguageEnglish
Detected LanguageEnglish
TypeThesis, doctoral, PhD
Rights<a rel="license" href="http://creativecommons.org/licenses/by-nc-nd/3.0/"><img alt="Creative Commons License" style="border-width:0" src="http://i.creativecommons.org/l/by-nc-nd/3.0/88x31.png" /></a><br />The University of Bradford theses are licenced under a <a rel="license" href="http://creativecommons.org/licenses/by-nc-nd/3.0/">Creative Commons Licence</a>.

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