| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Regular Articles |
1 Department of Health Sciences, University of Genoa, Genoa, Italy; 2 Washington University School of Medicine, St. Louis, Missouri; and 3 National Cancer Institute, Rockville, Maryland
We showed previously that p53 mutations play a role in cigarette smoke-related carcinogenesis not only in humans but also in A/J mice. In fact, (UL53–3 x A/J)F1 mice, carrying a dominant-negative germ-line p53 mutation, responded to exposure to environmental cigarette smoke more efficiently than their wild-type (wt) littermate controls in terms of molecular alterations, cytogenetic damage, and lung tumor yield. To clarify the mechanisms involved, we analyzed by cDNA array the expression of 1,185 cancer-related genes in the lung of the same mice. Neither environmental cigarette smoke nor the p53 status affected the expression of the p53 gene, but the p53 mutation strikingly increased the basal levels of p53 nuclear protein in the lung. Environmental cigarette smoke increased p53 protein levels in wt mice only. The p53 mutation enhanced the expression of positive cell cycle regulators in sham-exposed mice, which suggests a physiologic protective role of p53. In environmental cigarette smoke-exposed mice, the p53 mutation resulted in a lack of induction of proapoptotic genes and in overexpression of genes involved in cell proliferation, signal transduction, angiogenesis, inflammation, and immune response. Mutant mice and wt mice reacted to environmental cigarette smoke in a similar manner regarding genes involved in metabolism of xenobiotics, multidrug resistance, and protein repair. Irrespective of the p53 status, environmental cigarette smoke poorly affected the expression of oncogenes, tumor suppressor genes, and DNA repair genes. Taken together, these findings may explain the increased susceptibility of p53 mutant mice to smoke-related alterations of intermediate biomarkers and lung carcinogenesis.
This article has been cited by other articles:
|
|
 |
|
  F. D'Agostini, L. Mastracci, A. Izzotti, R. Balansky, T. M. Pennisi, V. E. Steele, and S. De Flora Modulation by Phenethyl Isothiocyanate and Budesonide of Molecular and Histopathologic Alterations Induced by Environmental Cigarette Smoke in Mice Cancer Prevention Research, June 1, 2009; 2(6): 546 - 556. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Izzotti, G. A. Calin, P. Arrigo, V. E. Steele, C. M. Croce, and S. De Flora Downregulation of microRNA expression in the lungs of rats exposed to cigarette smoke FASEB J, March 1, 2009; 23(3): 806 - 812. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Balansky, G. Ganchev, M. Iltcheva, V. E. Steele, F. D'Agostini, and S. De Flora Potent carcinogenicity of cigarette smoke in mice exposed early in life Carcinogenesis, October 1, 2007; 28(10): 2236 - 2243. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M.v. Leeuwen, E. v. Agen, R. W.H. Gottschalk, R. Vlietinck, M. Gielen, M. H.M.v. Herwijnen, L. M. Maas, J. C.S. Kleinjans, and J. H.M.v. Delft Cigarette smoke-induced differential gene expression in blood cells from monozygotic twin pairs Carcinogenesis, March 1, 2007; 28(3): 691 - 697. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. De Flora, F. D'Agostini, A. Izzotti, N. Zanesi, C. M. Croce, and R. Balansky Molecular and Cytogenetical Alterations Induced by Environmental Cigarette Smoke in Mice Heterozygous for Fhit Cancer Res., February 1, 2007; 67(3): 1001 - 1006. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. D'Agostini, A. Izzotti, R. Balansky, N. Zanesi, C. M. Croce, and S. De Flora Early loss of fhit in the respiratory tract of rodents exposed to environmental cigarette smoke. Cancer Res., April 1, 2006; 66(7): 3936 - 3941. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. D. Gross, J. O. Boyle, J. D. Morrow, M. K. Williams, C. S. Moskowitz, K. Subbaramaiah, A. J. Dannenberg, and A. J. Duffield-Lillico Levels of Prostaglandin E Metabolite, the Major Urinary Metabolite of Prostaglandin E2, Are Increased in Smokers Clin. Cancer Res., August 15, 2005; 11(16): 6087 - 6093. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
