GIBE (Grupo de Investigación en Biología Evolutiva), FCEyN-UBA, Facultad de Ciencias Exactas y Naturales, Instituto de Ecología, Genética y Evolución de Buenos Aires-Consejo de Investigaciones Científicas y Técnicas, Universidad de Buenos Aires (IEGEBA-CONICET), Ciudad Universitaria, Pabellón II, 4° Piso Laboratories. 43-46, C1428EGA, Buenos Aires, Argentina.
Laboratorio de Enzimología Estrés y Metabolismo, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Consejo de Investigaciones Científicas y Técnicas, Universidad de Buenos Aires (IQUIBICEN-CONICET),, Ciudad Universitaria, Pabellón II, 4° Piso Laboratories. 43-46, C1428EGA, Buenos Aires, Argentina.
Arch Toxicol. 2021 Mar;95(3):1071-1079. doi: 10.1007/s00204-020-02954-5. Epub 2020 Nov 27.
The fungicide Iprodione is widely applied in vegetables and raises concern for human health. The A549 human lung carcinoma cell line is a suitable model for assessing the toxicological effects of drugs. The goal of this work was to evaluate the genotoxicity and oxidative stress in the A549 cell line exposed to sublethal concentrations from 3 to 100 µg/mL Iprodione considering LC50 = 243.4 µg/mL Iprodione, as determined by the MTT assay. Generalized Linear Mixed Models (GLMM) were performed to determine the association between the responses NDI, MNi and MNi and the explanatory variables. Iprodione and solvent were relativized to the control whereas the concentration was included as numeric variable. ANOVA was used for the comparison of treatments. The coefficients of linear association between the explanatory variables and NDI, and the coefficients of logistic association between explanatory variables and MNi were not significant. However, these coefficients showed significant association with MNi only for Iprodione treatment but not for Iprodione concentration, indicating lack of dose-response relationship. Genotoxicity risk assessment indicated that the increase in Iprodione concentrations increased slightly the probability of belonging to the genotoxic category. ANOVA showed significant differences in MNi, and non-significant differences in NDI and MNi among treatments. The oxidative stress analysis performed at 3, 12, and 25 μg/mL Iprodione showed a significant and linear increase in SOD, and a significant and linear decrease in GSH and GST. The Dunnett test was significant for GSH at 12 and SOD at 25 μg/mL.
杀菌剂异菌脲广泛应用于蔬菜，引起了人们对人类健康的关注。A549 人肺癌细胞系是评估药物毒理学效应的合适模型。本工作的目的是评估亚致死浓度 3 至 100μg/mL 异菌脲暴露于 A549 细胞系的遗传毒性和氧化应激，LC50=243.4μg/mL 异菌脲，由 MTT 测定。广义线性混合模型（GLMM）用于确定 NDI、MNi 和 MNi 与解释变量之间的相关性。异菌脲和溶剂相对于对照进行了相对化，而浓度则作为数值变量包含在内。方差分析用于处理之间的比较。解释变量与 NDI 之间的线性关联系数和解释变量与 MNi 之间的逻辑关联系数均不显著。然而，这些系数仅与异菌脲处理而不是异菌脲浓度显著相关，表明缺乏剂量反应关系。遗传毒性风险评估表明，异菌脲浓度的增加略微增加了属于遗传毒性类别的概率。方差分析显示，MNi 存在显著差异，而 NDI 和 MNi 处理之间无显著差异。在 3、12 和 25μg/mL 异菌脲水平进行的氧化应激分析显示 SOD 呈显著线性增加，GSH 和 GST 呈显著线性下降。Dunnett 检验在 12μg/mL 时 GSH 和 25μg/mL 时 SOD 有意义。
