Genotoxicity of TiO₂ anatase nanoparticles in B6C3F1 male mice evaluated using Pig-a and flow cytometric micronucleus assays

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• 作者：Rakhshinda Sadiq^a ; ^b ; Javed A. Bhalli^a ; Jian Yan^a ; Robert S. Woodruff^c ; Mason G. Pearce^a ; Yan Li^a ; Thikra Mustafa^d ; Fumiya Watanabe^d ; Lindsay M. Pack^e ; Alexandru S. Biris^d ; Qaiser M. Khan^b ; Tao Chen^a ; ^{tao.chen@fda.hhs.gov}
• 关键词：Titanium dioxide nanoparticles ; Phosphatidylinositol glycan class A gene ; Flow cytometry ; CD24 ; %MN-RET frequency ; In vivo genotoxicity assays
• 刊名：Mutation Research/Genetic Toxicology and Environmental Mutagenesis
• 出版年：2012
• 期刊代码：31_13835718
• 类别：pha
• 出版时间：14 June, 2012
• 卷：745
• 期：1-2
• 页码：65-72
• 文件大小：1043 K

摘要

In vivo micronucleus and Pig-a (phosphatidylinositol glycan, class A gene) mutation assays were conducted to evaluate the genotoxicity of 10 nm titanium dioxide anatase nanoparticles (TiO₂-NPs) in mice. Groups of five 6-7-week-old male B6C3F1 mice were treated intravenously for three consecutive days with 0.5, 5.0, and 50 mg/kg TiO₂-NPs for the two assays; mouse blood was sampled one day before the treatment and on Day 4, and Weeks 1, 2, 4, and 6 after the beginning of the treatment; Pig-a mutant frequencies were determined at Day 鈭? and Weeks 1, 2, 4 and 6, while percent micronucleated-reticulocyte (%MN-RET) frequencies were measured on Day 4 only. Additional animals were treated intravenously with three daily doses of 50 mg/kg TiO₂-NPs for the measurement of titanium levels in bone marrow after 4, 24, and 48 h of the last treatment. The measurement indicated that the accumulation of the nanoparticles reached the peak in the tissue 4 h after the administration and the levels were maintained for a few days. No increase in either Pig-a mutant frequency or the frequency of%MN-RETs was detected, although the%RETs was reduced in the treated animals on Day 4 in a dose-dependent manner indicating cytotoxicity of TiO₂-NPs in the bone marrow. These results suggest that although TiO₂-NPs can reach the mouse bone marrow and are capable of inducing cytotoxicity, the nanoparticles are not genotoxic when assessed with in vivo micronucleus and Pig-a gene mutation tests.