Effects of fractionated x-irradiation on the Ly-6--Ril-1--Pol-5 region.
Our laboratory has focused on defining, localizing, and understanding the mode of action of genes involved in fractionated x-irradiation (FXI) leukemia in susceptible and restraint mouse strains. We have described the genetic and molecular evidence suggesting the existence of multiple independent loci involved in FXI-induced leukemogenesis. These studies indicated that one of these, Ril-1, a locus on the distal portion of chromosome 15, is the major locus influencing susceptibility to the disease. Our data unequivocally place Ril-1 in the gene complex Ly-6--Ril-1--Sis--H-30--Pol-5. Ril-1 appears to be closest to Ly-6 and Sis. We report that in FXI-induced leukemias there are hypomethylation changes in the Ly-6 region as compared to normal thymocytes. In contrast, Sis was found to be hypermethylated and not expressed. In addition, we have noted DNA rearrangements in the Ly-6--Pol-5 region in the majority of tumors examined using the Ly-6 and spleen focus-forming virus (SFFLV) molecular probes. Increased expression of Ly-6 and other surface markers encoded in this region has been noted in FXI-induced thymomas.
Department of Pathology, New York University Medical Center, NY 10016.
N M
NM
Amari
S
S
Kamiura
D
D
Meruelo
D000818:Animals; D015152:Blotting, Northern; D015139:Blotting, Southern; D002884:Chromosomes, Human, Pair 15 / Q000528:radiation effects*; D004247:DNA / Q000032:analysis; D015180:Electrophoresis, Gel, Two-Dimensional; D005434:Flow Cytometry; D015870:Gene Expression / Q000528:radiation effects; D015321:Gene Rearrangement / Q000528:radiation effects; D008040:Genetic Linkage; D006801:Humans; D007953:Leukemia, Radiation-Induced / Q000235:genetics*; D051379:Mice; D008815:Mice, Inbred Strains; D012150:Polymorphism, Restriction Fragment Length; D012313:RNA / Q000032:analysis; D011877:Radionuclide Imaging; D013945:Thymoma / Q000000981:diagnostic imaging / Q000235:genetics; D013953:Thymus Neoplasms / Q000000981:diagnostic imaging / Q000235:genetics; D014965:X-Rays / Q000009:adverse effects
D012313:RNA; D004247:DNA