Radiation-induced genomic instability and delayed activation of p53

Abstract

Recent studies have described that radiation induces genomic instability, which manifests in the progeny of surviving cells as a persistent decrease in plating efficiency (delayed reproductive death), increased chromosome instability, and increased mutation rate. Despite extensive studies into the process of delayed phenotypes, very little is known about the mechanism of genomic instability. Delayed chromosome instability is characterized by dicentric chromosomes, chromatid gaps and breaks, indicating that delayed DNA breakage is induced in the surviving cells several generations after irradiation. To determine the possibility, we have constructed a reporter plasmid containing the p53-responsible promoter and the β-galactosidase (β-gal) gene, and transfected the plasmid into human fibrosarcoma cells containing the wild-type p53 gene. The cells were irradiated with various doses of X-rays and plated to form the primary colonies. They were collected to perform the secondary colony formation, and we found that the expression of β-gal was frequently detected in the secondary colonies, derived from the primary colonies surviving X-rays. These observations indicate that p53 is frequently activated in the progeny of surviving cells, indicating that delayed DNA damage is responsible for the expression of delayed phenotypes.