Direct DNA interaction and genotoxic impact of three metals: Cadmium, nickel and aluminum
| Autor: | David Bergé-Lefranc, Florence Chaspoul, Catherine Belliardo, Philippe Gallice, Carole Di Giorgio |
|---|---|
| Přispěvatelé: | Aix-Marseille Université - Faculté de pharmacie (AMU PHARM), Aix Marseille Université (AMU), Institut méditerranéen de biodiversité et d'écologie marine et continentale (IMBE), Centre National de la Recherche Scientifique (CNRS)-Institut de recherche pour le développement [IRD] : UMR237-Aix Marseille Université (AMU)-Avignon Université (AU), Avignon Université (AU)-Aix Marseille Université (AMU)-Institut de recherche pour le développement [IRD] : UMR237-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
cadmium [SDV]Life Sciences [q-bio] chemistry.chemical_element DNA condensation medicine.disease_cause 03 medical and health sciences chemistry.chemical_compound nickel medicine [CHIM]Chemical Sciences General Materials Science A-DNA Physical and Theoretical Chemistry DNA binding Cadmium genotoxicity Isothermal titration calorimetry Phosphate Atomic and Molecular Physics and Optics isothermal titration calorimetry Comet assay 030104 developmental biology chemistry 13. Climate action aluminum Biophysics Genotoxicity DNA |
| Zdroj: | Journal of Chemical Thermodynamics Journal of Chemical Thermodynamics, Elsevier, 2018, 125, pp.271-277. ⟨10.1016/j.jct.2018.05.028⟩ Journal of Chemical Thermodynamics, 2018, 125, pp.271-277. ⟨10.1016/j.jct.2018.05.028⟩ |
| ISSN: | 0021-9614 1096-3626 |
| DOI: | 10.1016/j.jct.2018.05.028⟩ |
| Popis: | International audience; This study simultaneously investigates direct DNA interaction and genotoxic impact of three typical metals: aluminum, cadmium and nickel, which the high concentration in soils and which the industries use, result in a daily significant exposure to humans. The three of them are suspected to be involved in carcinogenesis which implies genomic lesions. We propose to first study their genotoxic impact in vivo on primary normal human dermal fibroblast (NHDF) cells with comet assay at pH 7 to measure DNA breaks occurrence. Then, to characterize the metal/DNA interaction by isothermal titration calorimetry (ITC). Comet assay shows that Cd and Ni are genotoxic, they are responsible for DNA breaks starting from 1.10-4 mol.L-1 and 5.10-2 mol.L-1, respectively whereas Al has no effect (on DNA at pH7) as studied by ITC at pH 7. Cd and Ni present an electrostatic interaction with DNA phosphate groups. At high Cd concentration, a DNA condensation is observed by contrast. Al has no interaction with DNA phosphate groups, but at pH 4 the electrostatic interaction is strong and the same DNA condensation phenomenon is observed. Metal genotoxic effect seems linked to the electrostatic interaction on DNA phosphate groups. Genotoxic power evolves in parallel to DNA phosphate interaction strength as Cd > Ni > Al. If this study shows that metals do not directly break DNA, this binding could be a preferential site for damage due to reactive oxygen species. |
| Databáze: | OpenAIRE |
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