Dose-independent genotoxic response in A549 cell line exposed to fungicide Iprodione
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GENOTOXICITY AND CARCINOGENICITY
Dose‑independent genotoxic response in A549 cell line exposed to fungicide Iprodione Nancy B. Andrioli1 · Gabriela Chaufan2 Received: 31 August 2020 / Accepted: 12 November 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract 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, MNim and M Nib 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 M Nim were not significant. However, these coefficients showed significant association with M Nib 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 MNib, and non-significant differences in NDI and M Nim 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. Keywords Cytotoxicity · Genotoxicity · Oxidative stress · Iprodione · A549 cell line
Introduction The application of agrochemicals has taken center stage in the global agricultural model. Fungicides are mainly used to control many pre- and postharvest diseases which * Nancy B. Andrioli [email protected] 1
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
2
cause rapid and extensive breakdown of high-moisture commodities, leading to serious economic problems (Smart 2003)
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