Evaluation of mutagenicity of zinc oxide nanoparticles by Pig-a mutation assay in vivo

Abstract

ObjectiveThe genotoxicity of zinc oxide nanoparticles （ZnO NPs） in rats was determined by Pig⁃a mutation assay in vivo.MethodsCombined with 28-day oral toxicity test， male SD rats were given ZnO NPs by oral administration for 28 days， at doses of 0， 14， 70 and 350 mg‧kg-1 （maximum concentration of nanoscale dispersion state）. Rats in control groups received 350 mg‧kg-1 of normal size ZnO， 40 mg‧kg-1 N-ethyl-N⁃nitrosourea（ENU）or 0 mg·kg-1 ZnO NPs（solvent control group） Changes of body weight were recorded. At 0， 15， 28 d and 28 d of recovery observation period， 200 μL of tail venous blood was collected from each group， which was labeled by APC mouse anti-rat erythroid cells and FITC mouse anti-rat CD59. The information of 1×106 red blood cells（RBC） from each sample were collected by flow cytometry， and the mutation rate of RBCCD59- was calculated.ResultsCompared with the solvent control group， after 15 days of intragastric administration， the mutation rate of RBC CD59- in peripheral blood of in 350 mg‧kg-1 ZnO NPs group and 40 mg‧kg-1 ENU group was significantly increased while that of in 70 mg‧kg-1 ZnO NPs group was also significantly increased after 28 days of intragastric administration.with time-response and dose-response relationship. All groups except 40 mg‧kg-1 ENU group showed no significant difference in the mutation rate of RBCCD59- in peripheral blood in comparison with the solvent control group after 28-days recovery observation.Conclusion70 and 350 mg‧kg-1 ZnO NPs can increase the mutation rate of Pig⁃a gene in peripheral blood of SD rats.

Keywords

• zinc oxide nanoparticle
• pig⁃a mutation assay
• mutagenicity
• time-response relationship
• dose-response relationship