Translocations in spleen cells from adult mice irradiated as fetuses are infrequent, but often clonal in nature.

We previously reported that mouse fetuses or neonates exposed to 2 Gy of X rays showed an unexpectedly low incidence of chromosome damage in lymphocytes, bone marrow, and spleen cells when the mice were subsequently examined at 20 weeks of age. However, cells bearing translocations were occasionally observed that, on the basis of 2-color whole chromosome painting appeared to be clonal descendants. Unfortunately, this approach typically did not permit unequivocal confirmation of their clonality. To overcome this problem, multi-color FISH (mFISH) was employed, which assigns all 21 individual chromosome types of the mouse a unique color. After mFISH analyses of the same cell samples studied previously, it was confirmed that spleen cells of 20-week-old mice irradiated either as 15.5-day fetuses or as 3- to 4-day-old neonates showed translocation frequencies close to zero. Translocations previously suspected as being clonal in nature were confirmed as such by mFISH, which also revealed the presence of an additional clone not previously detected or suspected. Since no evidence of clonality was observed in the irradiated mother, we concluded that in both fetuses and neonates, there exists a small fraction of stem cells that are distinct from the bulk of the stem cell compartment in terms of their ability to acquire and transmit radiation-induced chromosome damage through clonal expansion.