The effect of ionizing radiation on the response to erythropoietin of cultured rat marrow cells, at constant erythropoietin dose and constant cell density, differed according to the end point analyzed. Erythopoietin-induced RNA synthesis (an early response) and induced glucosamine incorporation into stroma (a late response) were relatively radioresistant. Induced hemoglobin synthesis was characterized by marked radiosensitivity. Inactivation parameters were n̄ = 1.04 and <tex-math>$D_{0}=63$</tex-math> R (59 rad) ± 15 R (95% confidence interval). The radiosensitivity was not the result of inactivation of secondary enzymic processes. The inactivation curves for stimulated hemoglobin synthesis at different doses of erythropoietin near the physiological range were found to be linear, with n̄ values in the range of 0.92 to 1.14. The corresponding log-log erythropoietin dose-response plots at different radiation doses were linear and parallel, a result inconsistent with an all-or-none action of radiation on erythropoietin-sensitive cells. At high cell density, the effect of 60 R on induced hemoglobin disappeared, whereas the effect on induced iron uptake persisted.

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