In vivo genotoxicity assessment of aluminium oxide nanomaterials in rat peripheral blood cells using the comet assay and micronucleus test

Abstract

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.