Lead contamination results in late and slowly repairable DNA double-strand breaks and impacts upon the ATM-dependent signaling pathways

Autor: Nicolas Foray, Jérôme Gastaldo, Aurélie Joubert, A. M. Charvet, Muriel Viau, Zuzana Bencokova, Jacques Balosso
Přispěvatelé: European Synchrotron Radiation Facility (ESRF), Rayonnement Synchrotron et Recherche Medicale (RSRM), European Synchrotron Radiation Facility (ESRF)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire Lésions des Acides Nucléiques (LAN), Service de Chimie Inorganique et Biologique (SCIB - UMR E3), Institut Nanosciences et Cryogénie (INAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS)-Institut Nanosciences et Cryogénie (INAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS), Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Département de cancérologie et d'hématologie, CHU Grenoble-Hôpital Michallon, Serduc, Raphael, Université Joseph Fourier - Grenoble 1 (UJF)-European Synchrotron Radiation Facility (ESRF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut Nanosciences et Cryogénie (INAC), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Institut de Radioprotection et de Sureté Nucléaire
Jazyk: angličtina
Rok vydání: 2007
Předmět:
MESH: Signal Transduction
Time Factors
DNA Repair
MESH: DNA Breaks
Double-Stranded
Cell Cycle Proteins
Ataxia Telangiectasia Mutated Proteins
DNA-Activated Protein Kinase
Toxicology
medicine.disease_cause
S Phase
MESH: Dose-Response Relationship
Drug
Histones
0302 clinical medicine
MRE11 Homologue Protein
DNA Breaks
Double-Stranded
MESH: Rad51 Recombinase
MESH: Endothelial Cells
Recombination
Genetic
Genetics
MESH: DNA Repair
MESH: Histones
0303 health sciences
MESH: Oxidative Stress
MESH: S Phase
General Medicine
3. Good health
Cell biology
DNA-Binding Proteins
MESH: Nitrates
030220 oncology & carcinogenesis
MESH: Recombination
Genetic
Signal transduction
MESH: Lead
Signal Transduction
G2 Phase
Programmed cell death
DNA damage
Protein Serine-Threonine Kinases
Biology
MESH: Protein-Serine-Threonine Kinases
Cell Line
03 medical and health sciences
MESH: X-Rays
MESH: Cell Cycle Proteins
MESH: Mutagens
medicine
Humans
MESH: Tumor Suppressor Proteins
Kinase activity
030304 developmental biology
Nitrates
MESH: Humans
Dose-Response Relationship
Drug
Tumor Suppressor Proteins
X-Rays
MESH: Time Factors
Endothelial Cells
MESH: Cell Line
Oxidative Stress
MESH: G2 Phase
Lead
13. Climate action
MESH: DNA-Activated Protein Kinase
Rad51 Recombinase
Homologous recombination
Genotoxicity
MESH: DNA-Binding Proteins
Mutagens
Zdroj: Toxicology Letters
Toxicology Letters, 2007, 173 (3), pp.201-14. ⟨10.1016/j.toxlet.2007.08.003⟩
Toxicology Letters, Elsevier, 2007, 173 (3), pp.201-14. ⟨10.1016/j.toxlet.2007.08.003⟩
ISSN: 0378-4274
1879-3169
DOI: 10.1016/j.toxlet.2007.08.003⟩
Popis: International audience; Despite a considerable amount of data, evaluation of the potential genotoxicity and cancer proneness of lead compounds remains unclear, probably due to the plethora of experimental procedures, biological endpoints and cellular models used. In parallel, the understanding in DNA damage formation, repair and signaling has considerably progressed all along these last years, notably for DNA double-strand breaks (DSBs). Here, were examined DNA damage formation and repair in human cells exposed to lead nitrate (Pb(NO(3))(2)) and their consequences upon the ATM-dependent stress signaling, cell cycle progression and cell death. As observed with anti-pH2AX immunofluorescence, exposure to Pb(NO(3))(2) results in formation of late DSBs, that would not originate from conversion of nucleotide damage but likely by a direct production of single-strand breaks. Lead contamination inhibits non-homologous end-joining repair process by preventing the DNA-PK kinase activity whereas the MRE11-dependent repair pathway is exacerbated. Lead contamination triggers successive synchronization of cells in G2/M phase in which the RAD51-dependent homologous recombination was found to be activated. Altogether, our findings support that lead contamination generates late unrepairable DSBs that impact upon the ATM-dependent stress signaling pathway by favoring propagation of errors. Such findings should help to consider more carefully the biological action of lead compounds in the frame of public and occupational exposures.
Databáze: OpenAIRE
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