Our experiments have focused on the analysis of residual haematopoietic damage in 8-day-old and 12-week-old mice X-irradiated with a single dose of 7 Gy. In the case of the adult mice, analysis of the femoral and splenic CFU-S, CFU-GM and BFU-E showed a persistent depletion of these haematopoietic progenitor cells after irradiation. In contrast, in 1-week-old irradiated mice, a progressive recovery of the femoral haematopoietic progenitors was observed, achieving essentially normal values 1 year after irradiation. The spleens of these mice, however, contained significantly less haematopoietic progenitors than the control group, mainly as a consequence of the size reduction of this organ. In the peripheral blood, normal cellularity values were observed in most cases, although in the adult group a decline in numbers or circulating cells was noted after the first year following irradiation. Long-term bone marrow cultures (LTBMCs) established 1 year after the irradiation of adult mice generated poor adherent layers, while confluent stromas were observed in flasks corresponding to 8-day-old irradiated mice. Analyses of the functional activity of granulocytes obtained from either the peripheral blood or LTBMCs revealed that both young and adult irradiated mice produced granulocytes generating high levels of superoxide anion, in relation to age-matched controls. This finding was correlated with a long-term microenvironmental activation which resulted in an overproduction of granulocyte-macrophage colony-stimulating factor.

This paper analyzes the long-term (6 and 12 months) function of mouse granulocytes after total body irradiation with a single dose (5 Gy) of X-rays. Superoxide anion production has been investigated in granulocytes from peripheral blood, and also in those harvested from long term bone marrow cultures, with the aim of correlating the environmental damage induced by radiation with the functional properties of granulocytes. An in vivo and in vitro enhancement of superoxide anion production and protein levels in granulocytes from irradiated mice is described. The presence of some colony stimulating factor in the supernatant of cultures from irradiated mice could play an important role in the priming of granulocytes.

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Summary.Our experiments focused on the metabolic implications of the residual haemopoietic damage in adult mice given 5 Gy X-rays. Bone marrow cells from irradiated mice exhibited an increase in protein synthesis and a decrease in ATP levels, which could be related to the enhancement of the proliferative activity of haemopoietic precursor cells. However, the kinetic parameters (V max and K m ) of glucose uptake, the glycolytic flux and the hexose monophospate (HMP) shunt activity were similar to those found in the control group. On the other hand, a reduction of glucose uptake (V max ) was found in both resting and stimulated granulocytes from irradiated mice. This reduction was accompanied by a decrease in the glycolytic rate and ATP levels. However, HMP shunt activity was similar in resting granulocytes in both the control and the irradiated mice. The stimulation by PMA produced a significantly higher increase in the activity of the pathway in granulocytes from the irradiated mice and was in accordance with the enhancement of superoxide anion production that has been previously described in these cells.