Radiation-induced germline instability at minisatellite loci

Abstract

Purpose: To review the results of recent studies on radiation induced germline instability at mammalian minisatellite loci. Results: Evidence has been obtained recently that germline mutation at minisatellites is remarkably sensitive to ionizing radiation, in both mice and humans. In mice, an elevated mutation rate was found after acute irradiation of pre-meiotic spermatogonia, with a doubling dose of 0.33Gy, a value close to those obtained in mice after acute spermatogonia irradiation using other systems for mutation detection. In humans, analysis of germline mutation rate at minisatellites among children born in areas of the Mogilev district of Belarus, which was heavily polluted after the Chernobyl accident, has shown a twofold higher mutation rate in exposed families compared with non-irradiated families from the United Kingdom. Within the Belarus cohort, the mutation rate was significantly greater in families exposed to a higher parental radiation dose, consistent with radiation induction of germline mutation. The data in this study also demonstrate the indirect nature of radiation-induced germline mutation at mammalian minisatellite loci suggesting a strong similarity with the phenomenon of genomic instability in somatic cells. Conclusions: Minisatellite loci provide a powerful system for the efficient monitoring of germline mutation in humans and are capable of detecting induced mutations in relatively small population samples.