Further studies on cyclic erythropoiesis in mice.

When young adult female W/Wv mice are given 0.5 micro+Ci 89Sr/g body weight intravenously, their hematocrit values oscillate from nadirs of 26% to zeniths of 42% with a periodicity of 16 days [1]. The response of the W/Wv mouse to an assortment of radioactive and hematologic stresses have been examined in an effort to understand better the pathophysiology of cyclic erythropoiesis. When the dose of 89Sr is increased, the amplitude of cycling increases as nadirs are lowered, but periodicity is unchanged. When the dose of 89Sr is lowered to 0.3 microCi or less, cyclic erythropoiesis of substantial amplitude is observed only after five or six microoscillations. A single hematopoietic insult of 80 rad x-irradiation coupled with phlebotomy produces a transient form of cyclic erythropoiesis, namely, a series of dampened oscillations prior to recovery. Finally, we report that Wv/Wv mice exhibit a form of cyclic erythropoiesis in response to 0.5 microCi 89Sr/g body weight, in which the hematocrit values of successive nadirs gradually increase, and stabilize at about 100 days. 89Sr does not induce cyclic erythropoiesis in the +/+, W/+, or W/v/+ mice, the Hertwig strain of anemic mice, or in normal BDF1 mice.

Cyclic erythropoiesis in the S1/S1d mouse.

Previously we reported that when young adult female W/Wv mice are given 0.5 microCi strontium-89 per gram body weight IV, their hematocrit values oscillate from nadirs of 26% to zeniths of 42% with a periodicity of 16 days. We now report that a second strain of congenitally anemic female mice, the S1/ S1d , also exhibit large fluctuations in their hematocrit values following a dose of 0.5 microCi 89Sr/g body weight. The zeniths through which these mice cycled averaged 37% (range 35%-38%) and the nadirs averaged 13% (range 12%-14%). Reticulocytes fluctuated from highs averaging 40% (range 35%-45%) to lows that averaged 3% (range 1%-5%). The periodicity of cycling in these eight mice ranged from 16 to 19 days. The hematocrits of three out of five non-strontium-treated mice were found to cycle spontaneously in the absence of 89Sr-mediated hematopoietic insult, with nadirs averaging 22% and zeniths averaging 39%. Similarly, doses as small as 0.1 microCi 89Sr/g body weight coupled with antecedent phlebotomy induced cyclic erythropoiesis of substantial amplitude (average nadir 16% and average zenith of 39%). Splenectomy in the S1/ S1d mouse eliminates both spontaneous and 89Sr-induced cyclic erythropoiesis. If the spleen is removed prior to radiostrontium treatment, then cyclic erythropoiesis is not observed following a dose of 0.5 microCi 89Sr/g body weight.

Cyclic erythropoiesis in W/Wv mice following a single small dose of 89Sr.

Young adult female W/Wv mice were given 0.5 microCi 89Sr/g intravenously, a dose which produces no anemia and only mild transient thrombocytopenia in normal mice. In the W/Wv animals platelet counts fell from 10(6) to 3 x 10(5)/mm3, and hematocrits from 39% to 25% in two weeks. In the following 2 weeks, platelet counts rose to 7 x 10(5), stabilizing at this level. Average hematocrit values were observed to oscillate from a nadir of 26% to a zenith of 42%, with a periodicity of about 16 days. In a repeat experiment we found the average hematocrit fluctuation from 28 to 40%, amplitude of reticulocyte fluctuation 6 to 31%, periodicity of cycle 16 days. Several animals have been observed through as many as six complete cycles. Further study of cyclical erythropoiesis in the W/Wv mouse following hematopoietic injury produced by 89Sr may shed light on the causes of cyclical hematopoiesis observed occasionally in man and other animals.

The erythropoietic effect, in mice, of androgens combined with hypoxia.

Progressively higher levels of erythrocytosis were observed in female mice residing at simulated altitudes of 9, 12, and 18 thousand feet. Administration of testosterone enhanced red-cell production in female mice under all but the most severe hypoxic conditions. The spleen contributed to the extent of erythropoiesis produced by hypoxia and by the combination of hypoxia and androgen, but this extramedullary site of red-cell formation was not necessary for erythrocytosis to occur. As little as 0.1 mg of testosterone enanthate weekly had an erythropoietic effect in female mice residing at 12,000 feet. Normal male mice also responded to hypoxia, but did not demonstrate a further erythropoietic effect in response to the concurrent administration of androgen.