Pretreatment with cytosine arabinoside does not protect against the delayed effects of irradiation on thrombopoiesis and erythropoiesis.
We have examined the capacity of the thrombopoietic and erythropoietic systems to respond to challenge with the cytotoxic drug 5-fluorouracil (5-FU) following sublethal doses of irradiation. Normal adult mice respond to 5-FU with a mild thrombocytopenia followed by a marked rebound thrombocytosis. One month after 2 Gy whole-body radiation, platelet counts took longer than normal to reach a nadir after 5-FU, and the rebound thrombocytosis was reduced. A normal response was seen when the interval after radiation was extended to 4 months. Increasing the radiation dose to 6.5 Gy resulted in a much smaller rebound thrombocytosis when 5-FU was given 1 month later. Extending the interval before the drug was given resulted in a normal response being regained between 4 and 7 months. Erythrocyte levels were temporarily depressed after 5-FU in all mice, and it took longer for recovery to occur if they had been irradiated. In another series of experiments, we investigated the effect of priming the mice before irradiation to see if this resulted in radioprotection. An injection of cytosine arabinoside (Ara-C) 2 days before a dose of 6.5 Gy resulted in the expected earlier recovery in platelet counts. To see if cells of the megakaryocyte lineage were protected from the delayed effects of irradiation by this treatment, mice were given 5-FU 1 month after Ara-C plus irradiation. The period of thrombocytopenia was followed by only a small rebound thrombocytosis, and platelet counts were indistinguishable from those found for mice not primed with Ara-C before irradiation. These experiments revealed a delayed effect of irradiation on the thrombopoietic and erythropoietic systems, which was long-lasting but not permanent at the doses used. The effects were not eliminated by priming mice with Ara-C before irradiation.
Peter MacCallum Cancer Institute, Melbourne, Australia.
J M
JM
Radley
L
L
Barber
G S
GS
Hodgson
D000818:Animals; D003561:Cytarabine / Q000494:pharmacology*; D004906:Erythrocyte Count; D004920:Erythropoiesis / Q000187:drug effects / Q000528:radiation effects*; D005472:Fluorouracil / Q000494:pharmacology; D006410:Hematopoiesis / Q000187:drug effects / Q000528:radiation effects*; D007700:Kinetics; D008297:Male; D008533:Megakaryocytes / Q000187:drug effects / Q000528:radiation effects*; D051379:Mice; D010976:Platelet Count; D014916:Whole-Body Irradiation
D003561:Cytarabine; D005472:Fluorouracil