Exposure to the Fungicide Captan Induces DNA Base Alterations and Replicative Stress in Mammalian Cells
| Autor: | Gladys Mirey, Elisa Boutet-Robinet, Julien Vignard, Anne Fernandez-Vidal, Liana C. Arnaud, Manon Maumus, Marianne Chevalier, Bernard Salles |
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| Rok vydání: | 2018 |
| Předmět: |
0303 health sciences
DNA synthesis Epidemiology DNA damage Health Toxicology and Mutagenesis Chinese hamster ovary cell food and beverages Mutagen 010501 environmental sciences medicine.disease_cause 01 natural sciences Cell biology Ames test 03 medical and health sciences chemistry.chemical_compound chemistry medicine Carcinogenesis Genetics (clinical) Captan Genotoxicity 030304 developmental biology 0105 earth and related environmental sciences |
| Zdroj: | Environmental and Molecular Mutagenesis. 60:286-297 |
| ISSN: | 0893-6692 |
| DOI: | 10.1002/em.22268 |
| Popis: | The classification of the fungicide captan (CAS Number: 133-06-2) as a carcinogen agent is presently under discussion. Despite the mutagenic effect detected by the Ames test and carcinogenic properties observed in mice, the genotoxicity of this pesticide in humans is still unclear. New information is needed about its mechanism of action in mammalian cells. Here, we show that Chinese Hamster Ovary (CHO) cells exposed to captan accumulate Fpg-sensitive DNA base alterations. In CHO and HeLa cells, such DNA lesions require the XRCC1-dependent pathway to be repaired. Captan also induces a replicative stress that activated the ATR signaling response and resulted in double-strand breaks and micronuclei. The replicative stress is characterized by a dramatic decrease in DNA synthesis due to a reduced replication fork progression. However, impairment of the XRCC1-related repair process did not amplify the replicative stress, suggesting that the fork progression defect is independent from the presence of base modifications. These results support the involvement of at least two independent pathways in the genotoxic effect of captan that might play a key role in carcinogenesis. Environ. Mol. Mutagen. 60:286-297, 2019. © 2018 Wiley Periodicals, Inc. |
| Databáze: | OpenAIRE |
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