title: Inhaled asbestos fibers induce p53 expression in the rat lung.
abstract: Humans and rodents exposed to an aerosol of asbestos fibers develop lung injury that can lead to a fibroproliferative response culminating in excessive scarring and impaired lung function. To define the early events that precede asbestos-induced fibrotic lung disease, rats were exposed to an aerosol of chrysotile asbestos fibers for 5 h. At various times after exposure, the lungs of the asbestos-exposed animals were evaluated immunohistochemically for expression of the p53 tumor suppressor protein, a growth regulatory protein. p53 became detectable by immunostaining at the predicted sites of fiber deposition (the bronchiolar-alveolar duct bifurcations) by 24 h after exposure. The number of cells positive for p53 immunostaining increased to a maximal level at 8 days after exposure, decreased by 14 days and returned to a low basal level at the 30-day time point. Control groups of rats that were unexposed or exposed to an aerosol of iron beads were negative for p53 immunostaining throughout the 30-day assessment period. Simultaneous detection of the proliferating cell nuclear antigen (PCNA) at the sites of fiber deposition in the asbestos-exposed animals agrees with our previous finding that p53 binds and regulates the PCNA promoter.
authors.affiliation: Department of Pathology, Tulane University Medical Center, New Orleans, Louisiana 70112, USA.
authors.forename: A
authors.initials: A
authors.lastname: Mishra
authors.forename: J Y
authors.initials: JY
authors.lastname: Liu
authors.forename: A R
authors.initials: AR
authors.lastname: Brody
authors.forename: G F
authors.initials: GF
authors.lastname: Morris
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D001194:Asbestos / Q000008:administration & dosage / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D016158:Genes, p53; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D001194:Asbestos