The relationships between p53 and radiation sensitivity are being investigated with mouse cell lines transfected with different forms of p53 mutations. The results will determine the phenotypic and functional changes of p53 and their involvement in the radiation sensitivity of mammalian cells. The goal of the interferon study is to investigate whether its effect on radiation sensitivity is mediated through the Ku 70/80 and DNA-dependent protein kinase (DNA-PK) activity. Ku 70/80 and DNA-PK are known to be involved in the repair of radiation-induced DNA double-strand breaks. A better understanding of the interaction between interferon beta and radiation would improve the efficacy of cancer therapy with combined treatments of radiation and drugs.

We are also studying the function of a yeast G2/M checkpoint gene, rad9, in mammalian cells. Mutation of rad9 in yeast abrogates the function of G2/M arrest and makes the cells very sensitive to ionizing radiation. We have identified a rad9 equivalent gene from the human lung tumor A549 cells. The expression of this gene as a function of the cell cycle is being investigated after various radiation conditions. We plan to explore the role of rad9 in G2/M arrest and radiation sensitivity of human tumor cells.

Helt CE, Staversky RJ, Lee YJ, Bambara RA, Keng PC,and O’Reilly MA. 2003. The CDK and PCNA domains on p21 Cip1 both function to inhibit G1/S progression during hyperoxia. Am J Physiol Lung Cell Mol Physiol. 2003 Aug 22

Roper JM, Staversky RJ, Finkelstein JN, Keng PC, and O’Reilly MA. 2003. Identification and isolation of mouse type II cells on the basis of intrinsic expression of enhanced green fluorescent protein. Am J Physiol Lung Cell Mol Physiol. Sep;285(3):L691-700.

Chen Y, Pandya K, Keng PC, Johnstone D, Li J, Lee YJ, Smudzin T, and Okunieff P. 2003. Phase I/II Clinical Study of Pulsed Paclitaxel Radiosensitization for Thoracic Malignancy: A Therapeutic Approach on the Basis of Preclinical Research of Human Cancer Cell Lines. Clin Cancer Res. Mar;9(3):969-975.

Roper JM, Staversky RJ, Finkelstein JN, Keng PC, and O’Reilly MA. 2003. Identification and isolation of mouse type II cells based upon intrinsic expression of enhanced green flourescent protein Am J Physiol Lung Cell Mol Physiol. 2003 May 9 [Epub ahead of print]

O’Reilly MA, Staversky RJ, Finkelstein JN, and Keng, PC. 2003. Activation of the G2 cell cycle checkpoint enhances survival of epithelial cells exposed to hyperoxia. Am J Physiol Lung Cell Mol Physiol. Feb;284(2):L368-375. Epub 2002 Oct 11.

Rancourt RC, Hayes DD, Chess PR, Keng PC, O'Reilly MA 2002. Growth arrest in G1 protects against oxygen-induced DNA damage and cell death. J Cell Physiol. Oct;193(1):26-36.

Matsui Y, Tsuchida Y, and Keng PC. 2001. Effects of p53 mutations on cellular sensitivity to ionizing radiation. Am J Clin Oncol. Oct;24(5):486-490.

O’Reilly MA, Staversky RJ, Watkins RH, Reed CK, de Mesy Jensen KL, Finkelstein JN, Keng PC. 2001. The cyclin-dependent kinase inhibitor p21 protects the lung from oxidative stress. Am J Respir Cell Mol Biol Jun;24(6):703-10.

Rancourt RC, Keng PC, Helt CE, and O'Reilly MA. 2001. The role of p21(CIP1/WAF1) in growth of epithelial cells exposed to hyperoxia. Am J Physiol Lung Cell Mol Physiol. Apr;280(4):L617-626.

O'Reilly, M.A., Staversky, R.J., Watkins, R.H., Maniscalco, W.M., and Keng, P.C. 2000. p53-independent induction of GADD45 and GADD153 in mouse lungs exposed to hyperoxia. Am. J. Physiol. 278:L552-L559.

Wheeler, K.T., Wang, L.M., Wallen, C.A., Childers, S.R., Cline, J.M., Keng, P.C., and Mach, R.H. 2000. Sigma-2 receptors as a biomarker of proliferation in solid tumours. Br. J. Cancer 82:1223-1232.

Lee, J., Moran, J.P., Fenton, B.M., Koch, C.J., Frelinger, J.G., Keng, P.C. and Lord, E.M. 2000. Alteration of tumour response to radiation by interleukin-2 gene transfer. Br. J. Cancer. 82:937-944.

Links are to the National Library of Medicine's PubMed publication database.