title: Crocidolite asbestos causes an induction of p53 and apoptosis in cultured A-549 lung carcinoma cells.
abstract: A number of genotoxic chemicals and agents, such as benzo(a)pyrene and ultraviolet light, are able to induce nuclear accumulation of p53 protein. Usually, this response is transient and a consequence of stabilization of the wild-type p53 protein. After withdrawal of the exposure, the amount of p53 protein returns to a normal level within hours or a few days. We have studied the p53 response to the exposure of crocidolite asbestos in A-549 lung carcinoma cells using three different methods, i.e., p53 immunohistochemistry, Western blotting and metabolic labelling followed by p53 immunoprecipitation. With these techniques we demonstrate a dose-dependent p53 nuclear response to crocidolite exposure. The half-life of p53 protein in A-549 lung carcinoma cells cultured in serum-free media increased from 30 up to 80 min, and the protein reacted with a wild-type specific antibody suggesting that it was in a wild-type conformation. In situ 3'-end labelling of A-549 cells demonstrated a dose-dependent increase in apoptotic activity. Our data support the idea that increased apoptotic activity, induced by crocidolite, is mediated by p53.
authors.affiliation: Department of Pathology, University of Oulu, Oulu, Finland. Paavo.Paako@oulu.fi
authors.forename: P
authors.initials: P
authors.lastname: Pääkkö
authors.forename: M
authors.initials: M
authors.lastname: Rämet
authors.forename: K
authors.initials: K
authors.lastname: Vähäkangas
authors.forename: N
authors.initials: N
authors.lastname: Korpela
authors.forename: Y
authors.initials: Y
authors.lastname: Soini
authors.forename: S
authors.initials: S
authors.lastname: Turunen
authors.forename: M
authors.initials: M
authors.lastname: Jaworska
authors.forename: A
authors.initials: A
authors.lastname: Gillissen