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: P Pääkkö, M Rämet, K Vähäkangas, N Korpela, Y Soini, S Turunen, M Jaworska, A Gillissen
• Journal: Apoptosis : an international journal on programmed cell death (Apoptosis) Vol. 3 Issue 3 Pg. 203-12 ( 1998) ISSN: 1360-8185 [Print] Netherlands
• PMID: 14646501 (Publication Type: Journal Article)