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In vivo radioprotective effects of recombinant human granulocyte colony-
stimulating factor in lethally irradiated mice
FM Uckun, L Souza, KG Waddick, M Wick and CW Song
Department of Therapeutic Radiology-Radiation Oncology, University of
Minnesota, Minneapolis.
The purpose of this study was to investigate the in vivo radioprotective
effects of recombinant human granulocyte colony stimulating factor
(rhG-CSF) in lethally irradiated BALB/c mice. We initially analyzed the
effects of increasing doses of rhG-CSF on survival of mice receiving 700
cGy (LD100/30) single dose total body irradiation (TBI). While 1
microgram/kg to 100 micrograms/kg doses of rhG-CSF were not
radioprotective, a dose-dependent radioprotection was observed at 200
micrograms/kg to 4,000 micrograms/kg rhG-CSF. We next compared four
different rhG-CSF treatment regimens side by side for their radioprotective
effects in LD100/30 irradiated mice. One hundred percent of control mice
receiving phosphate buffered saline died within 21 days after TBI with a
median survival of 14 days. The median survival was prolonged to 20 days
and the actuarial 60-day survival rate was increased to 27% when mice
received 2,000 micrograms/kg rhG- CSF 24 hours before TBI (P = .0002;
Mantel-Peto-Cox). Similarly, the median survival time was prolonged to 24
days and the actuarial 60-day survival rate was increased to 33%, when mice
were given 2,000 micrograms/kg rhG-CSF 30 minutes before TBI. Optimal
radioprotection was achieved when 2,000 micrograms/kg rhG-CSF was
administered in two divided doses of 1,000 micrograms/kg given 24 hours
before and 1,000 micrograms/kg given 30 minutes before TBI. This regimen
prolonged the median survival time of LD100/30 irradiated mice to more than
60 days and increased the actuarial 60-day survival rate to 62% (P = .0001;
Mantel-Peto-Cox). By comparison, no survival advantage was observed when
mice received rhG-CSF 24 hours post-TBI. Similar radioprotective effects
were observed when mice were irradiated with 650 cGy (LD80/30). The
presented findings provide conclusive evidence that rhG-CSF has significant
in vivo radioprotective effects for mice receiving LD100/30 or LD80/30 TBI.
Volume 75,
Issue 3,
pp. 638-645,
02/01/1990
Copyright © 1990 by The American Society of Hematology
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