This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ghosh, S. Articles by Morris, G. F. Search for Related Content PubMed PubMed Citation Articles by Ghosh, S. Articles by Morris, G. F.

Bleomycin Sensitivity of Mice Expressing Dominant-Negative p53 in the Lung Epithelium

Program in Lung Biology, Section of Pulmonary Diseases, Critical Care and Environmental Medicine; and Department of Pathology, Tulane/Xavier Center for Bioenvironmental Research and Tulane Cancer Center, New Orleans, Louisiana

Correspondence and requests for reprints should be addressed to Gilbert F. Morris, Department of Pathology, SL-79, Tulane University Health Sciences Center, 1430 Tulane Avenue, New Orleans, LA 70118. E-mail: gmorris2{at}tulane.edu

The chemotherapeutic drug bleomycin causes DNA damage and apoptosis in the lungs of mice within hours of endotracheal instillation followed by inflammation and fibrosis weeks later. The p53 tumor suppressor protein mediates cellular responses to DNA damage, including induction of apoptosis, but the effects of p53 activation in the various cell types of the lung during bleomycin-induced pulmonary fibrosis remain unclear. We show here that a transgene with a dominant-negative mutant form of human p53 expressed from the surfactant protein C promoter sensitizes mice to bleomycin-induced lung injury. The bleomycin-exposed transgenic animals display more severe lung pathology with associated collagen deposition and more pronounced lung eosinophilia than simultaneously exposed nontransgenic littermates. These observations suggest that compromising p53 function in the alveolar epithelium impairs recovery of the lung from bleomycin-induced injury.

Key Words: p53 • bleomycin • pulmonary fibrosis • transgenic mice

This article has been cited by other articles:

				S. Shetty, P. Shetty, S. Idell, T. Velusamy, Y. P. Bhandary, and R. S. Shetty Regulation of Plasminogen Activator Inhibitor-1 Expression by Tumor Suppressor Protein p53 J. Biol. Chem., July 11, 2008; 283(28): 19570 - 19580. [Abstract] [Full Text] [PDF]

				V. Panduri, S. Surapureddi, S. Soberanes, S. A. Weitzman, N. Chandel, and D. W. Kamp P53 Mediates Amosite Asbestos-Induced Alveolar Epithelial Cell Mitochondria-Regulated Apoptosis Am. J. Respir. Cell Mol. Biol., April 1, 2006; 34(4): 443 - 452. [Abstract] [Full Text] [PDF]

				M. E. Loewen and G. W. Forsyth Structure and Function of CLCA Proteins Physiol Rev, July 1, 2005; 85(3): 1061 - 1092. [Abstract] [Full Text] [PDF]

				W. E. Lawson, V. V. Polosukhin, O. Zoia, G. T. Stathopoulos, W. Han, D. Plieth, J. E. Loyd, E. G. Neilson, and T. S. Blackwell Characterization of Fibroblast-specific Protein 1 in Pulmonary Fibrosis Am. J. Respir. Crit. Care Med., April 15, 2005; 171(8): 899 - 907. [Abstract] [Full Text] [PDF]

				L. Wang, L. Bowman, Y. Lu, Y. Rojanasakul, R. R. Mercer, V. Castranova, and M. Ding Essential role of p53 in silica-induced apoptosis Am J Physiol Lung Cell Mol Physiol, March 1, 2005; 288(3): L488 - L496. [Abstract] [Full Text] [PDF]

				H Miyazaki, K Kuwano, K Yoshida, T Maeyama, M Yoshimi, M Fujita, N Hagimoto, R Yoshida, and Y Nakanishi The perforin mediated apoptotic pathway in lung injury and fibrosis J. Clin. Pathol., December 1, 2004; 57(12): 1292 - 1298. [Abstract] [Full Text] [PDF]

				G. F. Morris, A. R. Notwick, O. David, C. Fermin, A. R. Brody, and M. Friedman Development of Lung Tumors in Mutant p53-Expressing Mice After Inhalation Exposure to Asbestos Chest, May 1, 2004; 125(5_suppl): 85S - 86S. [Full Text] [PDF]

				M. J. Tobin Tuberculosis, Lung Infections, Interstitial Lung Disease, and Journalology in AJRCCM 2002 Am. J. Respir. Crit. Care Med., February 1, 2003; 167(3): 345 - 355. [Full Text] [PDF]