title: Bitumen products induce skin cell apoptosis in chronically exposed road pavers.
abstract: BACKGROUND
  Worker's exposure to bitumen fumes, via inhalation and skin contamination, is related to adverse effects including an increased risk of lung, stomach and non-melanoma skin cancers and leukaemia. The two major mechanisms regulating apoptosis include the mitochondria-mediated intrinsic pathway and the extrinsic pathway induced by death signalling ligands. In a previous study, we showed activation of apoptosis-regulating proteins BAX and BCL-2 in road pavers chronically exposed to bitumen fumes. These molecules play a central role in activation of programmed cell death by the intrinsic pathway. In this study, we hypothesized that the apoptosis mechanism could be activated in the skin of road pavers chronically exposed to bitumen fumes also through the extrinsic pathway, via mediation by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its death receptor, DR5.
  
  
  METHODS
  Skin punch biopsies from 16 occupationally exposed workers and a control group were processed immunohistochemically for TRAIL and DR5. Activation of programmed cell death was also investigated by expression of caspase-3 and visualization of DNA strand breaks.
  
  
  CONCLUSIONS
  TRAIL, DR5 and caspase-3 overexpression and enhanced Terminal Deoxynucleotidyl Transferase Mediated dUTP Nick End Labeling (TUNEL) positivity were found in chronically bitumen-exposed skin, suggesting activation of apoptosis as a defence mechanism.
authors.affiliation: Department of Molecular Pathology, Polytechnic University of Marche, Ancona, Italy.
authors.forename: Venerando
authors.initials: V
authors.lastname: Rapisarda
authors.forename: Maria L
authors.initials: ML
authors.lastname: Carnazza
authors.forename: Candida
authors.initials: C
authors.lastname: Caltabiano
authors.forename: Carla
authors.initials: C
authors.lastname: Loreto
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Musumeci
authors.forename: Matteo
authors.initials: M
authors.lastname: Valentino
authors.forename: Giuseppa
authors.initials: G
authors.lastname: Martinez
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001706:Biopsy; D053148:Caspase 3 / Q000096:biosynthesis*; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects; D005260:Female; D006801:Humans; D006838:Hydrocarbons / Q000633:toxicity*; D008297:Male; D009369:Neoplasms / Q000139:chemically induced / Q000473:pathology; D016273:Occupational Exposure / Q000009:adverse effects*; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000096:biosynthesis*; D012307:Risk Factors; D012867:Skin / Q000378:metabolism* / Q000473:pathology*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000096:biosynthesis*; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis
chemical_list: C494826:BAX protein, human; D006838:Hydrocarbons; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D051028:bcl-2-Associated X Protein; C006647:asphalt; C505407:CASP3 protein, human; D053148:Caspase 3