| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Departments of 1 Environmental Medicine, 2 Radiation Oncology, and 3 Pediatrics, University of Rochester, Rochester, New York 14642
Previous studies have shown that hyperoxia inhibits proliferation and increases the expression of the tumor suppressor p53 and its downstream target, the cyclin-dependent kinase inhibitor p21CIP1/WAF1, which inhibits proliferation in the G1 phase of the cell cycle. To determine whether growth arrest was mediated through activation of the p21-dependent G1 checkpoint, the kinetics of cell cycle movement during exposure to 95% O2 were assessed in the Mv1Lu and A549 pulmonary adenocarcinoma cell lines. Cell counts, 5-bromo-2'-deoxyuridine incorporation, and cell cycle analyses revealed that growth arrest of both cell lines occurred in S phase, with A549 cells also showing evidence of a G1 arrest. Hyperoxia increased p21 in A549 but not in Mv1Lu cells, consistent with the activation of the p21-dependent G1 checkpoint. The ability of p21 to exert the G1 arrest was confirmed by showing that hyperoxia inhibited proliferation of HCT 116 colon carcinoma cells predominantly in G1, whereas an isogenic line lacking p21 arrested in S phase. The cell cycle arrest in S phase appears to be a p21-independent process caused by a gradual reduction in the rate of DNA strand elongation. Our data reveal that hyperoxia inhibits proliferation in G1 and S phase and demonstrate that p53 and p21 retain their ability to affect G1 checkpoint control during exposure to elevated O2 levels.
p53; oxidants; cell proliferation
This article has been cited by other articles:
|
|
 |
|
  B. M. Fischer, S. Zheng, R. Fan, and J. A. Voynow Neutrophil elastase inhibition of cell cycle progression in airway epithelial cells in vitro is mediated by p27kip1 Am J Physiol Lung Cell Mol Physiol, September 1, 2007; 293(3): L762 - L768. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. C. Gehen, P. F. Vitiello, R. A. Bambara, P. C. Keng, and M. A. O'Reilly Downregulation of PCNA potentiates p21-mediated growth inhibition in response to hyperoxia Am J Physiol Lung Cell Mol Physiol, March 1, 2007; 292(3): L716 - L724. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Gong, H. Sohn, L. Xue, G. L. Firestone, and L. F. Bjeldanes 3,3'-Diindolylmethane Is a Novel Mitochondrial H+-ATP Synthase Inhibitor that Can Induce p21Cip1/Waf1 Expression by Induction of Oxidative Stress in Human Breast Cancer Cells. Cancer Res., May 1, 2006; 66(9): 4880 - 4887. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. S. Shenberger, J. L. Myers, S. G. Zimmer, R. J. Powell, and A. Barchowsky Hyperoxia alters the expression and phosphorylation of multiple factors regulating translation initiation Am J Physiol Lung Cell Mol Physiol, March 1, 2005; 288(3): L442 - L449. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. E. Helt, R. J. Staversky, Y.-J. Lee, R. A. Bambara, P. C. Keng, and M. A. O'Reilly The Cdk and PCNA domains on p21Cip1 both function to inhibit G1/S progression during hyperoxia Am J Physiol Lung Cell Mol Physiol, March 1, 2004; 286(3): L506 - L513. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. C. Das and R. Dashnamoorthy Hyperoxia activates the ATR-Chk1 pathway and phosphorylates p53 at multiple sites Am J Physiol Lung Cell Mol Physiol, January 1, 2004; 286(1): L87 - L97. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. O'Reilly, R. H. Watkins, R. J. Staversky, and W. M. Maniscalco Induced p21Cip1 in premature baboons with CLD: implications for alveolar hypoplasia Am J Physiol Lung Cell Mol Physiol, October 1, 2003; 285(4): L964 - L971. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. O'Reilly, R. J. Staversky, J. N. Finkelstein, and P. C. Keng Activation of the G2 cell cycle checkpoint enhances survival of epithelial cells exposed to hyperoxia Am J Physiol Lung Cell Mol Physiol, February 1, 2003; 284(2): L368 - L375. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. M. Maniscalco, R. H. Watkins, M. A. O'Reilly, and C. P. Shea Increased epithelial cell proliferation in very premature baboons with chronic lung disease Am J Physiol Lung Cell Mol Physiol, November 1, 2002; 283(5): L991 - L1001. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. C. Das and C. W. White Redox systems of the cell: Possible links and implications PNAS, July 23, 2002; 99(15): 9617 - 9618. [Full Text] [PDF]
|
|
|
|
|
|
M. A. O'Reilly DNA damage and cell cycle checkpoints in hyperoxic lung injury: braking to facilitate repair Am J Physiol Lung Cell Mol Physiol, August 1, 2001; 281(2): L291 - L305. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Tom, T. A. Ranalli, V. N. Podust, and R. A. Bambara Regulatory Roles of p21 and Apurinic/Apyrimidinic Endonuclease 1 in Base Excision Repair J. Biol. Chem., December 21, 2001; 276(52): 48781 - 48789. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
