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Crocidolite asbestos causes an induction of p53 and apoptosis in cultured A-549 lung carcinoma cells

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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.

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Authors
  1. P. Pääkkö
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  2. M. Rämet
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  3. K. Vähäkangas
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  4. N. Korpela
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  5. Y. Soini
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  6. S. Turunen
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  7. M. Jaworska
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  8. A. Gillissen
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Pääkkö, P., Rämet, M., Vähäkangas, K. et al. Crocidolite asbestos causes an induction of p53 and apoptosis in cultured A-549 lung carcinoma cells. Apoptosis 3, 203–212 (1998). https://doi.org/10.1023/A:1009655007284

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  • DOI: https://doi.org/10.1023/A:1009655007284

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