A molecular and genetic approach to understanding the mechanisms by which fractionated X-irradiation induces leukemia in mice.

Our laboratory's approach to try to shed light on the question of a viral etiology for radiation-induced leukemia has focused on defining, localizing and understanding the mode of action of genes involved in susceptibility to FXI-induced disease. These studies have indicated that multiple genes control the process of leukemogenesis. In addition not every mouse strain which shows some susceptibility to FXI-induced leukemia carries the susceptible gene at each of the multiple loci involved in the disease process. Thus, it is plausible to conclude that more than one mechanism of leukemogenesis can be triggered by FXI. Our studies have focused on the mode of action of one such locus Ril-1. Several reagents have been developed to help us clone and characterize this locus. Currently chromosomal "walking" and "hopping" techniques are being used in conjunction with an RFLP molecular probe which is adjacent to Ril-1. In addition a cDNA library has been prepared from a radiation-induced thymoma and subtraction hybridization analysis is being used in the search for Ril-1.