title: Wood dust exposure induces cell transformation through EGFR-mediated OGG1 inhibition.
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.
authors.affiliation: Department of Clinical and Molecular Science.
authors.forename: Sara
authors.initials: S
authors.lastname: Staffolani
authors.affiliation: Department of Clinical and Molecular Science.
authors.forename: Nicola
authors.initials: N
authors.lastname: Manzella
authors.affiliation: Department of Clinical and Molecular Science.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Strafella
authors.affiliation: Department of Clinical and Molecular Science.
authors.forename: Linda
authors.initials: L
authors.lastname: Nocchi
authors.affiliation: Department of Clinical and Molecular Science.
authors.forename: Massimo
authors.initials: M
authors.lastname: Bracci
authors.affiliation: Department of Clinical and Molecular Science.
authors.forename: Veronica
authors.initials: V
authors.lastname: Ciarapica
authors.affiliation: Department of Clinical and Molecular Science.
authors.forename: Monica
authors.initials: M
authors.lastname: Amati
authors.affiliation: Department of Biomedical Sciences and Public Health.
authors.forename: Corrado
authors.initials: C
authors.lastname: Rubini
authors.affiliation: Department of Clinical Sciences, Polytechnic University of Marche, via Tronto, 10A, 60020 Ancona, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Re
authors.affiliation: Department of Clinical and Molecular Science.
authors.forename: Armanda
authors.initials: A
authors.lastname: Pugnaloni
authors.affiliation: UOC-ORL Budrio-Metropolitan Hospital Via Benni, 44, Budrio 40054, Bologna, Italy and.
authors.forename: Ernesto
authors.initials: E
authors.lastname: Pasquini
authors.affiliation: Department of E.N.T. Polyclinic 'Sant'Orsola Malpighi' Otolaryngology Clinic, University of Bologna Via Pietro Albertoni, 15, 40138, Bologna, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Tarchini
authors.affiliation: Department of Clinical and Molecular Science.
authors.forename: Matteo
authors.initials: M
authors.lastname: Valentino
authors.affiliation: Department of Clinical and Molecular Science, m.tomasetti@univpm.it.
authors.forename: Marco
authors.initials: M
authors.lastname: Tomasetti
authors.affiliation: Department of Clinical and Molecular Science.
authors.forename: Lory
authors.initials: L
authors.lastname: Santarelli
mesh_terms: D017209:Apoptosis; D015153:Blotting, Western; D001980:Bronchi / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002478:Cells, Cultured; D045647:DNA Glycosylases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D004391:Dust; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology*; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D018919:Neovascularization, Physiologic; D016273:Occupational Exposure / Q000009:adverse effects*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D014934:Wood / Q000737:chemistry*
chemical_list: D004391:Dust; D012333:RNA, Messenger; C000624653:TSC2 protein, human; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins; C546842:MTOR protein, human; C512478:EGFR protein, human; D066246:ErbB Receptors; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human