Evaluation of the cytotoxic and genotoxic potential of the captan-based fungicides, chlorothalonil-based fungicides and methyl thiophanate-based fungicides in human fibroblasts BJ

Abstract

The objectives of this study were to examine cytotoxic and genotoxic damage in human BJ fibroblasts caused by three pesticides used worldwide by trypan blue dye exclusion assays and to measure the relative level of phosphorylated histone H2A.X by flow cytometry at different concentrations. Captan-based fungicide and methyl thiophanate-based fungicide (100 and 1000 µΜ) showed immediate cytotoxic effects; furthermore, after 24 h, captan-based fungicide, chlorothalonil-based fungicide and methyl thiophanate-based fungicide caused cytotoxic effects in the concentration ranges of 40–100 µM, 30–100 µM and 150–1000 µM, respectively. All fungicides generated DNA damage in the treated cells by activating ATM and H2A.X sensor proteins. The three fungicides tested generated DNA double-stranded breaks and showed cytotoxicity at concentrations 33, 34, and 5 times lower (captan, chlorothalonil and thiophanate-methyl respectively) than those used in the field, as recommended by the manufacturers.

Keywords:

• Genotoxicity
• cytotoxicity
• fungicide
• viability
• phosphorylation

Acknowledgments

The authors acknowledge Consejo Nacional de Ciencia y Tecnología (CONACYT) under project number 2018-000068-02NACF-23822 for the scholarship awarded to the main author. This work was conducted as part of the activities of the Laboratorio Nacional de Investigación y Desarrollo de Radiofármacos, Conacyt.