Recent in vivo and in vitro data of patients analyzed for genetic susceptibility 
to radiation during cancer therapy have shown structural changes in the 
chromosomes to be prevalent both in the patients being treated and in their 
immediate family members. As structural changes in chromosomes frequently lead 
to activation of proto-oncogenes and elimination of tumor-suppressor genes, they 
represent important mechanisms for the initiation of DNA repair processes and 
tumorigenesis. With the exception of rare genetic syndromes such as AT (Ataxia 
telangiectasia) or NBS (Nijmegen Breakage Syndrome), the background for the 
inheritance of genetic susceptibility to radiation is unknown. Recently, a 
large-scale genetic screen of mouse mutants has been established within the 
German Human Genome Project (Hrabè de Angelis and Balling 1998). The goal of 
this ENU (ENU: ethylnitrosourea) mutagenesis screen is the generation of mutant 
mice that will serve as animal models for human diseases and genetic 
susceptibility. In order to fully utilize the potential of a genetic screen of 
this magnitude, in which exploration for genes responsible for genomic 
instability and radiation sensitivity is to occur, it is necessary to establish 
a simple assay system that is amenable to automation. Hence, we are using the 
single-cell gel electrophoresis (comet assay) to detect mouse mutants that 
display a genetic susceptibility to ionizing radiation. We have established the 
analysis parameters in the comet assay which are currently used to detect 
radiation-sensitive mouse mutants and to control the variance within the mouse 
population in the ENU screen. The assay can be used to isolate genes that are 
responsible for DNA repair and radiation sensitivity in mouse and human.