Cell and Molecular Biology of Ataxia Telangiectasia Heterozygous Human Mammary Epithelial Cells Irradiated in Culture
Abstract
The goal of this research is to define markers expressed in clinically normal human mammary epithelial cells (HMEC) such that a molecular epidemiological model of ionizing radiation-induced cancer may be considered. This approach has value since existing predictive models for radiogenic late effects have high uncertainty, and since tools of molecular biology have recently advanced such that molecular epidemiology is now a good investigative area for advancing predictive risk modeling. Early markers related to carcinogenic pathway are identified for examination as panels of protein expression to be probed in HMEC in tissue culture irradiated or not with cesium-137 gamma rays. Panels of markers chosen relate to the dynamics of extracellular matrix, the architecture of the cell, and the repair of DNA-damage and control of cell proliferation. Marker-expression is determined as a function of age (passage number) and phase of growth (log versus plateau) of HMEC. Whereas any specific malignant cancer is likely to be of clonal origin, it is hypothesized that predictive value of some early markers reside in their widespread expression in populations of irradiated HMEC as field effects that promote selection of genetically altered cells providing the malignant phenotype. It is found that expression of ATM gene product, p53, estrogen receptor, cytokeratin 18, and apparent apoptosis-related nuclear fragmentation are altered as field effects in irradiated HMEC, and may thus be - considered for use in the assessment of carcinogenic risk of ionizing radiation.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2002
- Accession Number
- ADA412826
Entities
People
- Robert C. Richmond
Organizations
- National Aeronautics and Space Administration