Megakaryocyte DNA content and platelet formation in rats after a sublethal dose of thio-TEPA.
The megakaryocytopoiesis in rats was studied following a single dose of thio-TEPA to determine the mechanisms for the thrombocytopenia and subsequent recovery. The blood platelet number, platelet production (measured by 35S incorporation into platelets), mean platelet volume, and the number and DNA content of bone marrow megakaryocytes (MK) were observed. The blood platelet counts, platelet production, and total MK number decreased to low values following the administration of thio-TEPA, and stayed low until regeneration started around day 10. The mean platelet volume increased from the normal 6.6 fl to 7.8 fl during the early regeneration days 8-14. The MK were divided into four ploidy classes: 2N-4N, 8N, 16N, and 32N-64N. The number of MK within all ploidy classes decreased to nearly zero within four days after the injection of thio-TEPA. The regeneration started around day 10 with increasing numbers of 2N-4N and 8N MK, while the number of 16N and 32N-64N MK increased more than four days later. It is concluded that decreased or blocked influx of progenitor cells into the MK compartment is the main reason for thrombocytopenia after exposure to thio-TEPA.
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D000818:Animals; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects*; D002452:Cell Count / Q000187:drug effects; D004247:DNA / Q000378:metabolism*; D006410:Hematopoiesis / Q000187:drug effects*; D008297:Male; D008533:Megakaryocytes / Q000187:drug effects* / Q000378:metabolism; D010976:Platelet Count / Q000187:drug effects; D011003:Ploidies / Q000187:drug effects; D051381:Rats; D011917:Rats, Inbred Lew; D013852:Thiotepa / Q000633:toxicity*
D004247:DNA; D013852:Thiotepa