Recent developments in molecular biology have stimulated general interest in the genetic determinants of radiation sensitivity. Since late S phase is the most radiation resistant portion of the cell cycle to ionizing radiation, elucidation of the genetic regulatory mechanisms of the G1/S cell cycle transition would likely be fundamental to an understanding of cellular radiation sensitivity. Both the putative tumor suppressor gene, p53 and the G1/S cyclin, cyclin D1 or PRAD-1, serve as genetic regulatory elements at the G1/S boundary. Potential associations among cell cycle alterations, periodic changes in levels of expression of these genes, and phenotypic changes in cellular radiation sensitivity remain poorly characterized. Transfection studies of both primary rat embryo cells (REC) and human glioblastoma cell lines will reveal how p53 and PRAD-1 affect the phenotypes of cellular radiation sensitivity, cell cycle kinetics, and in vivo tumorigenicity. Cell kinetic analyses of transfected cells will lead to a better understanding of basic mechanisms of cell cycle control, both prior to as well as following irradiation. The role that WAF-1(CIP-1), -a gene regulated by both p53 and cyclin D1, plays in the modulation of the intrinsic radiation sensitivity and cell cycle kinetics of transfected cellular populations will be examined. The proposed program of investigation should thus not only lead to a better understanding of cellular radiation sensitivity, as it relates to basic mechanisms of cell cycle regulation, but may serve to unify concepts in radiation biology and molecular biology.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Clinical Investigator Award (CIA) (K08)
Project #
1K08CA001761-01A1
Application #
2084432
Study Section
Cancer Institutional Fellowship Review Committee (CT)
Project Start
1995-09-01
Project End
1996-06-30
Budget Start
1995-09-01
Budget End
1996-06-30
Support Year
1
Fiscal Year
1995
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02199
Pardo, Francisco S; Aronen, Hannu J; Fitzek, Markus et al. (2004) Correlation of FDG-PET interpretation with survival in a cohort of glioma patients. Anticancer Res 24:2359-65