Wood dust exposure induces cell transformation through EGFR-mediated OGG1 inhibition
| Autor: | Armanda Pugnaloni, Elisabetta Strafella, Monica Amati, Sara Staffolani, Matteo Valentino, Paolo Tarchini, Linda Nocchi, Veronica Ciarapica, Massimo Bracci, Corrado Rubini, Massimo Re, Ernesto Pasquini, Nicola Manzella, Marco Tomasetti, Lory Santarelli |
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| Rok vydání: | 2015 |
| Předmět: |
DNA damage
DNA repair Health Toxicology and Mutagenesis Blotting Western Cell Neovascularization Physiologic Apoptosis Bronchi Real-Time Polymerase Chain Reaction Toxicology complex mixtures DNA Glycosylases Immunoenzyme Techniques chemistry.chemical_compound Occupational Exposure Tuberous Sclerosis Complex 2 Protein Botany Genetics medicine Humans Neoplastic transformation RNA Messenger Phosphorylation Protein kinase B Cells Cultured Genetics (clinical) PI3K/AKT/mTOR pathway Carcinogen Cell Proliferation Reverse Transcriptase Polymerase Chain Reaction TOR Serine-Threonine Kinases Tumor Suppressor Proteins Dust Epithelial Cells Wood Cell biology ErbB Receptors Cell Transformation Neoplastic medicine.anatomical_structure chemistry Proto-Oncogene Proteins c-akt DNA |
| Zdroj: | Mutagenesis. 30:487-497 |
| ISSN: | 1464-3804 0267-8357 |
| DOI: | 10.1093/mutage/gev007 |
| Popis: | A high risk of neoplastic transformation of nasal and paranasal sinuses mucosa is related to the occupational exposure to wood dust. However, the role of occupational exposures in the aetiology of the airway cancers remains largely unknown. Here, an in vitro model was performed to investigate the carcinogenic effect of wood dusts. Human bronchial epithelial cells were incubated with hard and soft wood dusts and the DNA damage and response to DNA damage evaluated. Wood dust exposure induced accumulation of oxidised DNA bases, which was associated with a delay in DNA repair activity. By exposing cells to wood dust at a prolonged time, wood dust-initiated cells were obtained. Initiated-cells were able to form colonies in soft agar, and to induce blood vessel formation. These cells showed extensive autophagy, reduced DNA repair, which was associated with reduced OGG1 expression and oxidised DNA base accumulation. These events were found related to the activation of EGFR/AKT/mTOR pathway, through phosphorylation and subsequent inactivation of tuberin. The persistence in the tissue of wood dusts, their repetitious binding with EGFR may continually trigger the activation switch, leading to chronic down-regulation of genes involved in DNA repair, leading to cell transformation and proliferation. |
| Databáze: | OpenAIRE |
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