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使用染色体畸变、微核、精液分析和随机扩增多态性DNA图谱对口服给药后的瑞士小鼠体内氧化锌纳米颗粒进行遗传毒性评估。

Genotoxicity evaluation of zinc oxide nanoparticles in Swiss mice after oral administration using chromosomal aberration, micronuclei, semen analysis, and RAPD profile.

作者信息

Srivastav Anurag Kumar, Kumar Akhilesh, Prakash Jyoti, Singh Dhirendra, Jagdale Pankaj, Shankar Jai, Kumar Mahadeo

机构信息

1 Biochemistry Laboratory, Animal Facility, Regulatory Toxicology Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Lucknow, Uttar Pradesh, India.

2 Amity Institute of Biotechnology, Amity University, Lucknow Campus, Lucknow, Uttar Pradesh, India.

出版信息

Toxicol Ind Health. 2017 Nov;33(11):821-834. doi: 10.1177/0748233717717842. Epub 2017 Sep 26.

Abstract

The expanded uses of zinc oxide nanoparticles (ZnO NPs) have grown rapidly in the field of nanotechnology. Thus, rising production of nanoparticles (NPs) increases the possible risks to the environment and occupationally exposed humans. Hence, it is indispensable to appraise the safety toxicity including genotoxicity for these NPs. In the present study, we have evaluated the genotoxic effect of ZnO NPs after oral administration to Swiss mice at dose levels of 300 and 2000 mg/kg body weight. These doses were administered for 2 days at 24 h apart. Chromosomal aberration (CA) and micronucleus tests were conducted following Organization for Economic Co-operation and Development guidelines. DNA damage was evaluated at 0, 24, 48, and 72 h posttreatment using a randomly amplified polymorphic DNA (RAPD) assay; additionally, semen analyses were also performed at 34.5 days post oral exposure. The reactive oxygen species (ROS), 8-oxo-2'-deoxyguanosine and CAs were increased ( p < 0.05) at the highest dosage (2000 mg/kg) of ZnO NPs compared to controls. Aberrant sperm morphology with reduced sperm count and motility were also present ( p < 0.05) in the high-dose group. Based on the RAPD assay, the genomic template stability within the high-dose group (<90%) was less than the controls (100%). The results suggested that ZnO NPs are mildly genotoxic in a dose-related manner and this toxicity were induced by generation of ROS.

摘要

氧化锌纳米颗粒(ZnO NPs)在纳米技术领域的应用迅速扩展。因此,纳米颗粒(NPs)产量的增加会加大对环境和职业暴露人群的潜在风险。所以,评估这些纳米颗粒的安全毒性,包括遗传毒性是必不可少的。在本研究中,我们评估了以300和2000毫克/千克体重的剂量水平给瑞士小鼠口服ZnO NPs后的遗传毒性作用。这些剂量每隔24小时给药2天。按照经济合作与发展组织的指导方针进行染色体畸变(CA)和微核试验。在治疗后0、24、48和72小时,使用随机扩增多态性DNA(RAPD)分析评估DNA损伤;此外,在口服暴露后34.5天也进行了精液分析。与对照组相比,在ZnO NPs最高剂量(2000毫克/千克)时,活性氧(ROS)、8-氧代-2'-脱氧鸟苷和染色体畸变增加(p<0.05)。高剂量组中还出现了精子形态异常、精子数量减少和活力降低的情况(p<0.05)。基于RAPD分析,高剂量组(<90%)的基因组模板稳定性低于对照组(100%)。结果表明,ZnO NPs具有轻度的剂量相关遗传毒性,这种毒性是由ROS的产生诱导的。

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