EVIDENCE FOR AN UNCOMMON MICROSATELLITE INSTABILITY ON MOUSE-CHROMOSOME-2 AND MOUSE-CHROMOSOME-4 AND ITS POSSIBLE ROLE IN RADIATION LEUKEMOGENESIS

Although microsatellite instability (MSI), usually detected by DNA len gth polymorphisms, has been implicated in the induction of solid tumor s in both humans and animals, its role in leukemogenesis is unclear. T he goal of this study was to investigate whether there is an associati on between MSI and radiation leukemogenesis in CBA/Ca mice, Microsatel lite lengths at 55 loci, mapped to eight different mouse chromosomes, were examined in two groups of DNA samples: 1) 10 normal DNA samples c ollected from the bone marrow cells of control male CBA/Ca mice, and 2 ) 17 DNA samples isolated from the spleens of mice that developed myel oid leukemia (ML) after exposure to neutrons, or X rays, or gamma rays . Microsatellite markers were amplified using the non-radioisotopic mu ltiplex-touchdown PCR protocols developed in our laboratory, and the s izes of amplicons were examined on 6% non-denaturing polyacrylamide ge ls, Although no correlation between microsatellite length polymorphism s and radiation leukemogenesis was observed at the 55 CBA/Ca mouse loc i tested in this study, an uncommon MSI, manifested as the absence of DNA bands after PCR amplification at 2 loci (D2MIT140 and D4MIT104), w as observed in both control and ML samples. However, the frequency of ML samples showing this type of MSI is statistically significant (p<0. 05). Although there is no direct evidence that this type of MSI predis poses mice to the development of leukemia, the results suggests that g enes flanking the D2MIT140 and D4MIT104 are susceptible to spontaneous mutation and perhaps to damage caused by ionizing radiation.