We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Wood dust exposure induces cell transformation through EGFR-mediated OGG1 inhibition.
- Authors
Staffolani, Sara; Manzella, Nicola; Strafella, Elisabetta; Nocchi, Linda; Bracci, Massimo; Ciarapica, Veronica; Amati, Monica; Rubini, Corrado; Re, Massimo; Pugnaloni, Armanda; Pasquini, Ernesto; Tarchini, Paolo; Valentino, Matteo; Tomasetti, Marco; Santarelli, Lory
- Abstract
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.
- Subjects
WOOD dust; CELL transformation; EPIDERMAL growth factor receptors; DNA repair; THRESHOLD limit values (Industrial toxicology)
- Publication
Mutagenesis, 2015, Vol 30, Issue 4, p487
- ISSN
0267-8357
- Publication type
Article
- DOI
10.1093/mutage/gev007