DNA Double-Strand Breaks Induced in Human Cells by 6 Current Pesticides: Intercomparisons and Influence of the ATM Protein
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 jo...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-02-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/12/2/250 |
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| author | Laurène Sonzogni Mélanie L. Ferlazzo Adeline Granzotto Béatrice Fervers Laurent Charlet Nicolas Foray |
| author_facet | Laurène Sonzogni Mélanie L. Ferlazzo Adeline Granzotto Béatrice Fervers Laurent Charlet Nicolas Foray |
| author_sort | Laurène Sonzogni |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T22:30:08Z |
| format | Article |
| id | doaj.art-b356214ec444426a854b47bfaca269ed |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-09T22:30:08Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-b356214ec444426a854b47bfaca269ed2023-11-23T18:58:53ZengMDPI AGBiomolecules2218-273X2022-02-0112225010.3390/biom12020250DNA Double-Strand Breaks Induced in Human Cells by 6 Current Pesticides: Intercomparisons and Influence of the ATM ProteinLaurène Sonzogni0Mélanie L. Ferlazzo1Adeline Granzotto2Béatrice Fervers3Laurent Charlet4Nicolas Foray5INSERM U1296 Unit “Radiation: Defense, Health, Environment”, Centre Léon-Bérard, 69008 Lyon, FranceINSERM U1296 Unit “Radiation: Defense, Health, Environment”, Centre Léon-Bérard, 69008 Lyon, FranceINSERM U1296 Unit “Radiation: Defense, Health, Environment”, Centre Léon-Bérard, 69008 Lyon, FranceINSERM U1296 Unit “Radiation: Defense, Health, Environment”, Centre Léon-Bérard, 69008 Lyon, FranceISTerre Team, University Grenoble Alpes, 38000 Grenoble, FranceINSERM U1296 Unit “Radiation: Defense, Health, Environment”, Centre Léon-Bérard, 69008 Lyon, FranceA 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.https://www.mdpi.com/2218-273X/12/2/250pesticidestoxicityDNA double-strand breaksATMimmunofluorescence |
| spellingShingle | Laurène Sonzogni Mélanie L. Ferlazzo Adeline Granzotto Béatrice Fervers Laurent Charlet Nicolas Foray DNA Double-Strand Breaks Induced in Human Cells by 6 Current Pesticides: Intercomparisons and Influence of the ATM Protein Biomolecules pesticides toxicity DNA double-strand breaks ATM immunofluorescence |
| title | DNA Double-Strand Breaks Induced in Human Cells by 6 Current Pesticides: Intercomparisons and Influence of the ATM Protein |
| title_full | DNA Double-Strand Breaks Induced in Human Cells by 6 Current Pesticides: Intercomparisons and Influence of the ATM Protein |
| title_fullStr | DNA Double-Strand Breaks Induced in Human Cells by 6 Current Pesticides: Intercomparisons and Influence of the ATM Protein |
| title_full_unstemmed | DNA Double-Strand Breaks Induced in Human Cells by 6 Current Pesticides: Intercomparisons and Influence of the ATM Protein |
| title_short | DNA Double-Strand Breaks Induced in Human Cells by 6 Current Pesticides: Intercomparisons and Influence of the ATM Protein |
| title_sort | dna double strand breaks induced in human cells by 6 current pesticides intercomparisons and influence of the atm protein |
| topic | pesticides toxicity DNA double-strand breaks ATM immunofluorescence |
| url | https://www.mdpi.com/2218-273X/12/2/250 |
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