Molecular mechanisms of radiation-induced genomic instability in human cells

The overall strategy was to create a series of isogenic human cell lines that differ in key elements of cell cycle checkpoint, apoptosis, or DNA repair in response to radiation-induced damage. The goal then was to quantify the fractions of cells within a population that exhibit reduced telomere lengths and relate this to the genetic background of the cell, as well as to the response to ionizing radiation. Association between telomere length and degree of genomic instability in the population is being examined for seven closely related cell lines, that vary in p53 status, bcl-2 status, or ability to repair double strand breaks. Experiments utilize gamma rays at doses of 0, 10, and 200 cGy. During this time period the effort concentrated on generating data with two cell lines. Approximately one-third of the required clones were isolated, and analyses for mutagenesis and chromosome aberrations were undertaken