体内 <b><i>Pig-a</i></b> 基因突变实验评估纳米氧化锌致突变性

成雪晴; 杨隽; 刘玺; 邵乃敏; 洪新宇

doi:10.19428/j.cnki.sjpm.2022.21549

体内 Pig-a 基因突变实验评估纳米氧化锌致突变性

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

摘要

摘要:
目的利用体内Pig⁃a基因突变实验方法，检测纳米氧化锌（ZnO NPs）颗粒对大鼠遗传毒性的作用。
方法结合28 d经口毒性试验，设14、70、350 mg‧kg^-1 ZnO NPs（纳米尺度分散状态最大浓度）3个剂量组、常规ZnO组（350 mg‧kg^-1 ZnO）、阳性对照组（40 mg‧kg^-1N⁃亚硝基⁃N⁃乙基脲）和溶剂对照组（0 mg‧kg^-1 ZnO NPs），每组各10只大鼠经口灌胃28 d，记录并观察体重变化。在给药0、15、28 d和恢复观察期28 d取各组大鼠尾静脉血200 μL，用APC mouse anti⁃rat erythroid cells及FITC mouse anti⁃rat CD59抗体进行标记后，使用流式细胞仪收集各样本1×10⁶个红细胞信息，计算其中外周血红细胞CD59缺失突变发生率。
结果与溶剂对照组比较，在灌胃15 d后，350 mg‧kg^-1ZnO NPs组、阳性对照组大鼠外周血红细胞CD59缺失突变发生率均升高，差异均有统计学意义（均P<0.01）；在灌胃28 d后，70 mg‧kg^-1 ZnO NPs组、350 mg‧kg^-1 ZnO NPs组和阳性对照组大鼠红细胞CD59缺失突变发生率均升高，且呈时⁃效和量⁃效关系；在停止灌胃28 d后，除阳性对照组外，其余各组大鼠外周血红细胞CD59缺失发生率与溶剂对照组比较差异均无统计学意义（均P>0.05）。
结论 70、350 mg‧kg^-1 ZnO NPs会提高大鼠外周血Pig⁃a基因突变率。

Abstract:
Objective The genotoxicity of zinc oxide nanoparticles （ZnO NPs） in rats was determined by Pig⁃a mutation assay in vivo.
Methods Combined 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^-1N-ethyl-N⁃nitrosourea（ENU）or 0 mg·kg^-1ZnO 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 RBC^CD59-was calculated.
Results Compared 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 RBC^CD59- in peripheral blood in comparison with the solvent control group after 28-days recovery observation.
Conclusion 70 and 350 mg‧kg^-1 ZnO NPs can increase the mutation rate of Pig⁃a gene in peripheral blood of SD rats.

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