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Genotoxicity assessment of a selected cytostatic drug mixture in human lymphocytes: A study based on concentrations relevant for occupational exposure
Environmental Research ( IF 8.3 ) Pub Date : 2017-12-26 , DOI: 10.1016/j.envres.2017.10.044
Goran Gajski , Carina Ladeira , Marko Gerić , Vera Garaj-Vrhovac , Susana Viegas

Cytostatic 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.



中文翻译:

人体淋巴细胞中选定的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

抑制细胞生长的药物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,但它们已被认为对职业​​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剂的暴露可能会比单一物质产生更高的风险。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)的所选细胞抑制剂混合物在体外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,而且还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,这项研究提供了新的数据集,这些数据对于在职业和环境环境中对细胞抑制药物混合物进行基于科学的风险评估是必要的。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,这项研究提供了新的数据集,这些数据对于在职业和环境环境中对细胞抑制药物混合物进行基于科学的风险评估是必要的。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,这项研究提供了新的数据集,这些数据对于在职业和环境环境中对细胞抑制药物混合物进行基于科学的风险评估是必要的。

更新日期:2017-12-26
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