Study of the Effects of Chemotherapeutic Agents on the “Early” and “Late” Responses to Erythropoietin ∗

Summary

Dactinomycin in doses, 0,01 μg/gm 4 times 1/hour, which markedly depress the effect measured 48 hours after erythropoietin (EP) injection (“late” response) does not affect that measured 24 hours after EP injection (“early” response). Methotrexate 0.5 mg/kg followed 4 hours later by 3 mg of leucovorin, completely supresses the “early” response when given 4 hours after EP. The effect of methotrexate on the “late” response is phasic: Minimum when given together with, maximum when given either 4 hours before or after. Vinblastine supresses both the “early” and “late” response, although larger doses are required to affect the “early” response. The data are discussed in relation to the difference between the “early” and “late” responses and the involvement in both of cells in reproductive cycle. The “late” response would reflect differentiation of EP responsive cells in cycle, while the “early” response would reflect entry into cycle of erythroid cells which, in the absence of EP, would not have divided.