DNA Double-Strand Breaks Induced in Human Cells by 6 Current Pesticides: Intercomparisons and Influence of the ATM Protein

Biomolecules

Adeline Granzotto¹  Mélanie L. Ferlazzo¹  Béatrice Fervers¹  Laurène Sonzogni¹  Nicolas Foray¹  Laurent Charlet² 

[1] INSERM U1296 Unit “Radiation: Defense, Health, Environment”, Centre Léon-Bérard, 69008 Lyon, France;ISTerre Team, University Grenoble Alpes, 38000 Grenoble, France;

关键词: pesticides;    toxicity;    DNA double-strand breaks;    ATM;    immunofluorescence;   

DOI  :  10.3390/biom12020250

来源: DOAJ

【 摘 要 】

A mechanistic model from radiobiology has emerged by pointing out that the radiation-induced nucleo-shuttling of the ATM protein (RIANS) initiates the recognition, the repair of DNA double-strand breaks (DSB), and the final response to genotoxic stress. More recently, we provided evidence in this journal that the RIANS model is also relevant for exposure to metal ions. To document the role of the ATM-dependent DSB repair and signaling after pesticide exposure, we applied six current pesticides of domestic and environmental interest (lindane, atrazine, glyphosate, permethrin, pentachlorophenol and thiabendazole) to human skin fibroblast and brain cells. Our findings suggest that each pesticide tested may induce DSB at a rate that depends on the pesticide concentration and the RIANS status of cells. At specific concentration ranges, the nucleo-shuttling of ATM can be delayed, which impairs DSB recognition and repair, and contributes to toxicity. Interestingly, the combination of copper sulfate and thiabendazole or glyphosate was found to have additive or supra-additive effects on DSB recognition and/or repair. A general mechanistic model of the biological response to metal and/or pesticide is proposed to define quantitative endpoints for toxicity.

【 授权许可】

Unknown