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喹乙醇诱导雄性和雌性外周血淋巴细胞氧化应激及细胞毒性和遗传毒性。

Quinocetone triggers oxidative stress and induces cytotoxicity and genotoxicity in human peripheral lymphocytes of both genders.

机构信息

Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

出版信息

J Sci Food Agric. 2013 Apr;93(6):1317-25. doi: 10.1002/jsfa.5891. Epub 2012 Oct 2.

Abstract

BACKGROUND

Quinocetone has been widely used as an animal growth promoter in China. However, available data showed that QCT has potential genotoxicity. This study was conducted to investigate the cytotoxicity and genotoxicity of QCT in human lymphocytes.

RESULTS

CCK-8 assay demonstrated the severe inhibitory effects by QCT in a dose- and time-dependent manner. DNA damage analysis using alkalic Comet assay revealed a pronounced increase of DNA fragmentation in cells. In contrast, DNA damage was significantly decreased after incubation with S9 mix. This finding demonstrated that the intermediate metabolites of this drug exerted lower genotoxicity than its parent drugs. We further described chromosomal damage induced by this drug employing cytokinesis-block micronucleus assay. The micronucleus frequency was significantly increased in quinocetone groups as compared to controls. Similar to the observation in Comet assay, incorporation of S9 mix in the cytokinesis-block micronucleus assay could markedly alleviate the chromosomal damage. Moreover, QCT could invoke increase of reactive oxygen species generation in cells. Intriguingly, the toxicity of QCT was more prominent in samples from males than those from females under the same conditions.

CONCLUSION

QCT could induce potential cytotoxicity and genotoxicity in human lymphocytes.

摘要

背景

在中国,喹乙醇被广泛用作动物生长促进剂。然而,现有数据表明 QCT 具有潜在的遗传毒性。本研究旨在探讨 QCT 对人淋巴细胞的细胞毒性和遗传毒性。

结果

CCK-8 检测结果表明,QCT 呈剂量和时间依赖性严重抑制细胞生长。采用碱性彗星试验分析 DNA 损伤,结果显示细胞中的 DNA 片段化明显增加。相比之下,用 S9 混合物孵育后,DNA 损伤显著降低。这一发现表明该药物的中间代谢物的遗传毒性低于其母体药物。我们进一步采用细胞有丝分裂阻断微核试验描述了该药物引起的染色体损伤。与对照组相比,喹乙醇组的微核频率明显增加。与彗星试验的观察结果相似,在细胞有丝分裂阻断微核试验中加入 S9 混合物可显著减轻染色体损伤。此外,QCT 可引起细胞内活性氧物质的产生增加。有趣的是,在相同条件下,QCT 对男性样本的毒性比女性样本更为明显。

结论

QCT 可诱导人淋巴细胞潜在的细胞毒性和遗传毒性。

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