A METHOD FOR INVESTIGATION OF STEMCELL KINETICS
A new radiobiologic method for investigation of stem cells is presented and some limitations of the Fe/sup 59/ method of estimating erythropoiesis are pointed out. The technique was conducted by giving young adult mice two daily intraperitoneal injections of homologous red cells. By 5 days after the second transfusion, erythrocyte formation was almost completely eliminated, and at varying times after total-body x irradiation, the functional integrity of the stem-cell compartment was tested by determining the response to a subcutaneous stimulating dose of 6 units of erythropoietin per mouse. Forty-eight hr later, when the wave of erythropoiesis induced by erythropoietin was entering its late stage, 5 mu C of Fe/sup 59/Cl/sub 3/ was administered intraperitoneally. Seventy-two hr after the injection of radioiron, animals were sacrificed and the per cent radioiron incorporated by newly formed erythrocytes was determined. A plot of Fe/sup 59/ incorporated into newly formed erythrocytes against the radiation dose in roentgens yielded a curve with a 37% dose slope of about a10 rad and an extrapolation number (to no radiation) of about 1.2 to 1.3. When the incorporation of radioiron was plotted as a function of the time between irradiation and administration of erythropoietin, a dip in the number of available stem cells 24 hr after irradiation was seen. At 5 days after irradiation the stem-cell compartment was not appreciably more receptive to the stimulating action of a standard dose of erythropoietin than it was immediately after irradiation. Recovery was then rapid, however, and in the next 24 hr became complete. The erythropoietic response, as measured by incorporation of a tracer dose of Fe/sup 59/, to 6 units of erythropoietin was as effective 6 or 7 days after 150 r as it is in nonirradiated mice. The sequence of events are described as: immediate damage (at 0 time), postirradiation dip (at 24 hr), abortive recovery (48 hr to 5 days), and ultimate recovery (5 to 7 days). Serum Fe levels rose sharply in the normal rat following whole-body irradiation; however, such a change does not occur in transfused rats. This is due to the striking reduction in erythropoiesis prior to irradiation, and to the greatly elevated plasma iron resulting from the daily breakdown of the increased red-cell mass. Nevertheless, the plasma iron would be expected to fall when erythropoiesis is reinstituted in the polycythemic animal by erythropoietin. This fall is probably progressively less as the radiation dose increases and inhibits response to erythropoietin. Consequently, suitable corrections for this have to be made. (BBB)
- Research Organization:
- Churchill Hospital, Oxford
- Sponsoring Organization:
- USDOE
- NSA Number:
- NSA-18-015833
- OSTI ID:
- 4070233
- Journal Information:
- Brit. J. Haematol., Vol. Vol: 8; Other Information: Orig. Receipt Date: 31-DEC-64
- Country of Publication:
- Country unknown/Code not available
- Language:
- English
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