Forced differentiation of CFU-s by iron-55 erythrocytocide

Cascades of Auger electrons are emitted in the decay of 55Fe and absorbed in tissue within a 1 μm radius. Cytocidal amounts of 55Fe can therefore eliminate erythroid precursors with minimal damage to adjacent cells. Early events leave the granuloid series undisturbed but they are accompanied by a precipitous fall of pluripotent stem cells levels (CFU-s) in bone marrow, spleen, and blood. The pretreatment levels of CFU-s are not restored. Gradual decline of CFU-s is associated with intermittently increased turnover rate and reduced settings of cell production, yet unimpaired capacity for quick restoration of blood loss. The precipitous initial stem cell decrease is not caused by irradiation damage as shown in a separate experimental series which uses the frozen-storage cytocide technique. Only over several weeks could 55Fe radiation accumulate to lethal levels in nondividing stem cells. This irradiation is attributed to incorporation of small amounts of 55Fe into CFU-s from where it is slowly cleared. The stem cell loss immediately following 55Fe injection is in our interpretation caused by rapid differentiation along the erythroid pathway in a response that involves all progenitor populations. Data are consistent with the hypothesis of limited cell renewal capacity which thereby gains further support