5-fluorouracil-induced thrombocytosis in mice is independent of the spleen and can be partially reproduced by repeated doses of cytosine arabinoside.
Experiments were done to characterize the pronounced and prolonged thrombocytosis that develops in mice during recovery from the marrow hypoplastic effects of a single injection of 5-fluorouracil (5-FU). Measurements were made of platelet and megakaryocyte numbers, size of mature megakaryocytes, marrow cellularity, hematocrit, and reticulocytes. Mice that had been splenectomized a month before receiving 5-FU displayed the same pattern of thrombocytosis as intact mice, so a role for the spleen in its genesis or persistence could not be identified. During recovery from two or three doses of cytosine arabinoside (Ara-C), given at intervals of 2 days, thrombocytosis and megakaryocytosis of similar magnitudes to those seen after 5-FU occurred. Bone marrow cellularity, hematocrits, and reticulocytes were identical after three doses of Ara-C or one dose of 5-FU. Megakaryocytes were initially macrocytic during recovery from the hypoplastic thrombocytopenia produced by 5-FU or Ara-C. These similarities to effects of repeated doses of Ara-C suggested that some of the effects of 5-FU were due to its prolonged action in vivo, which could cause sequential killing of proliferating cells. Abnormalities of megakaryocytes and platelets reversed promptly when normal or increased numbers of megakaryocytes and/or platelets were produced after Ara-C, but they persisted in mice that received 5-FU. This difference suggested that regulation of megakaryocyte progenitors was perturbed during recovery from 5-FU.
Ebbe
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Lawrence Berkeley Laboratory, University of California, Berkeley 94720.
Yee
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T
Phalen
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D000818:Animals; D001854:Bone Marrow Cells; D003561:Cytarabine / Q000494:pharmacology*; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology*; D008533:Megakaryocytes / Q000166:cytology; D051379:Mice; D010976:Platelet Count / Q000187:drug effects; D012156:Reticulocytes / Q000166:cytology; D013154:Spleen / Q000502:physiology*; D013922:Thrombocytosis / Q000139:chemically induced*; D013997:Time Factors
D003561:Cytarabine; D005472:Fluorouracil