Abstract Genotoxicity assessment of a selected cytostatic drug mixture in human lymphocytes: A study based on concentrations relevant for occupational exposure
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Genotoxicity assessment of a selected cytostatic drug mixture in human lymphocytes: A study based on concentrations relevant for occupational exposure

机译：人体淋巴细胞中所选抑癌药物混合物的遗传毒性评估：一项基于与职业接触有关的浓度的研究

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摘要

AbstractCytostatic drugs are highly cytotoxic agents used in cancer treatment and although their benefit is unquestionable, they have been recognized as hazardous to healthcare professionals in occupational settings. In a working environment, simultaneous exposure to cytostatics may occur creating a higher risk than that of a single substance. Hence, the present study evaluated the combined cyto/genotoxicity of a mixture of selected cytostatics with different mechanisms of action (MoA; 5-fluorouracil, cyclophosphamide and paclitaxel) towards human lymphocytes in vitro at a concentration range relevant for occupational as well as environmental exposure. The results suggest that the selected cytostatic drug mixture is potentially cyto/genotoxic and that it can induce cell and genome damage even at low concentrations. This indicates not only that such mixture may pose a risk to cell and genome integrity, but also that single compound toxicity data are not sufficient for the prediction of toxicity in a complex working environment. The presence of drugs in different amounts and with different MoA suggests the need to study the relationship between the presence of genotoxic components in the mixture and the resulting effects, taking into account the MoA of each component by itself. Therefore, this study provides new data sets necessary for scientifically-based risk assessments of cytostatic drug mixtures in occupational as well as environmental settings.Highlights•A cytostatic drug mixture was tested in human peripheral blood cells.•The mixture induced cyto/genotoxic effects.•Cytostatic drug combinations can pose risks to human health in occupational setting.•Further toxicological assessment of cytostatic drug mixtures are needed.
机译： 摘要 抑癌药是用于癌症治疗的高度细胞毒性药物，尽管其益处毋庸置疑，但已被认为对职业​​环境中的医疗保健专业人员有害。在工作环境中，同时发生细胞生长抑制因子暴露的风险可能高于单一物质。因此，本研究评估了具有不同作用机制（MoA； 5-氟尿嘧啶，环磷酰胺和紫杉醇）的不同细胞抑制剂混合物对人淋巴细胞的综合细胞毒性/遗传毒性，其浓度范围与职业暴露和环境暴露有关。结果表明，所选的抑癌药物混合物可能具有细胞毒性/遗传毒性，即使在低浓度下也可以诱导细胞和基因组损伤。这不仅表明这种混合物可能对细胞和基因组完整性造成威胁，而且表明单一化合物的毒性数据不足以预测复杂工作环境中的毒性。考虑到每种成分本身的MoA，存在不同数量且MoA不同的药物提示需要研究混合物中遗传毒性成分的存在与产生的影响之间的关系。因此，本研究提供了在职业和环境条件下对基于细胞抑制药物混合物进行科学风险评估所需的新数据集。 < ce：abstract xmlns：ce =“ http://www.elsevier.com/xml/common/dtd” xmlns =“ http://www.elsevier.com/xml/ja/dtd” id =“ ab0015” class = “ author-highlights” view =“ all”> 突出显示 < ce：simple-para id =“ sp0035” view =“ all”> • 在人的外周血细胞中测试了一种抑制细胞生长的药物混合物。 • 混合物诱导了细胞/遗传毒性作用。 • 镇静药物组合可能对人类健康构成威胁在职业设置。 • 需要对细胞抑制药物混合物进行进一步的毒理学评估。

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  • 来源
    《Environmental research》 |2018年第2期|26-34|共9页
  • 作者

    Goran Gajski; Carina Ladeira; Marko Gerić; Vera Garaj-Vrhovac; Susana Viegas;

  • 作者单位

    Mutagenesis Unit, Institute for Medical Research and Occupational Health;

    Grupo de Investigação em Ambiente e Saúde, Escola Superior de Tecnologia da Saúde de Lisboa, Instituto Politécnico de Lisboa,Grupo de Investigação em Genética e Metabolismo, Escola Superior de Tecnologia da Saúde de Lisboa, Instituto Politécnico de Lisboa;

    Mutagenesis Unit, Institute for Medical Research and Occupational Health;

    Mutagenesis Unit, Institute for Medical Research and Occupational Health;

    Grupo de Investigação em Ambiente e Saúde, Escola Superior de Tecnologia da Saúde de Lisboa, Instituto Politécnico de Lisboa,Centro de Investigação em Saúde Pública, Escola Nacional de Saúde Pública, Universidade NOVA de Lisboa;

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  • 正文语种 eng
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  • 关键词

    5-fluorouracil; Cyclophosphamide; Paclitaxel; Human lymphocytes; Cyto/genotoxicity;

    机译：5-氟尿嘧啶;环磷酰胺;紫杉醇;人类淋巴细胞;细胞毒性/遗传毒性;

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