Mutagenesis Advance Access originally published online on February 23, 2009
Mutagenesis 2009 24(3):245-251; doi:10.1093/mutage/gep003
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In vivo genotoxicity assessment of aluminium oxide nanomaterials in rat peripheral blood cells using the comet assay and micronucleus test
Toxicology Unit, Biology Division, Indian Institute of Chemical Technology, Hyderabad 500 607, Andhra Pradesh, India 1Applied Biotechnology, Air Force Research Laboratory/HEPB, Wright-Patterson, AFB, OH 45431, USA
Advances in nanotechnology and its usage in various fields have led to the exposure of humans to engineered nanomaterials (NMs) and there is a need to tackle the potential human health effects before these materials are fully exploited. The main purpose of the current study was to assess whether aluminium oxide NMs (Al2O3-30 nm and Al2O3-40 nm) could cause potential genotoxic effects in vivo. Characterization of Al2O3-30 nm and Al2O3-40 nm was done with transmission electron microscopy, dynamic light scattering and laser Doppler velocimetry prior to their use in this study. The genotoxicity end points considered in this study were the frequency of micronuclei (MN) and the percentage of tail DNA (% Tail DNA) migration in rat peripheral blood cells using the micronucleus test (MNT) and the comet assay, respectively. Genotoxic effects were evaluated in groups of female Wistar rats (five per group) after single doses of 500, 1000 and 2000 mg/kg body weight (bw) of Al2O3-30 nm, Al2O3-40 nm and Al2O3-bulk. Al2O3-30 nm and Al2O3-40 nm showed a statistically significant dose-related increase in % Tail DNA for Al2O3-30 nm and Al2O3-40 nm (P < 0.05). However, Al2O3-bulk did not induce statistically significant changes over control values. The MNT also revealed a statistically significant (P < 0.05) dose-dependent increase in the frequency of MN, whereas Al2O3-bulk did not show any significant increase in frequency of MN compared to control. Cyclophosphamide (40 mg/kg bw) used as a positive control showed statistically significant (P < 0.001) increase in % Tail DNA and frequency of MN. The biodistribution of Al2O3-30 nm and Al2O3-40 nm and Al2O3-bulk in different rat tissues, urine and feces was also studied 14 days after treatment using inductively coupled plasma mass spectrometry. The data indicated that tissue distribution of Al2O3 was size dependent. Our findings suggest that Al2O3 NMs were able to cause size- and dose-dependent genotoxicity in vivo compared to Al2O3-bulk and control groups.
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Received on November 20, 2008; revised on December 31, 2008; accepted on January 6, 2009.