Protective, restorative, and therapeutic properties of recombinant colony-stimulating factors.
Pretreatment of mice with recombinant murine (rM) colony-stimulating factor-granulocyte-macrophage (CSF-gm) or recombinant human (rH) CSF-g provides partial protection from the lethal effects of ionizing radiation or the alkylating agent cyclophosphamide (CTX). In addition, these agents can significantly prolong survival if administered following lethal doses of irradiation or CTX. To induce protective activity, cytokines were injected 20 hours before lethal irradiation or CTX administration. To accelerate recovery from lethal irradiation, the cytokines must be administered shortly following irradiation, and the induction of maximal levels of activity is dependent on chronic administration. In contrast, because of their longer half-lives, accelerated recovery from alkylating agents requires a delay of at least 24 to 48 hours to allow complete clearance of CTX before administration of a CSF. Studies quantitating peripheral blood leukocytes and bone marrow cellularity as well as colony-forming units per culture (CFU-C) frequency and CFU-C per femur revealed a significant correlation between these parameters and the ability to survive lethal irradiation. This is a US government work. There are no restrictions on its use.
Talmadge
J E
JE
Program Resources, Inc, National Cancer Institute-Frederick Cancer Research Facility, MD.
Tribble
H
H
Pennington
R
R
Bowersox
O
O
Schneider
M A
MA
Castelli
P
P
Black
P L
PL
Abe
F
F
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology; D016026:Bone Marrow Transplantation; D003114:Colony-Forming Units Assay; D003115:Colony-Stimulating Factors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000633:toxicity; D004334:Drug Administration Schedule; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006410:Hematopoiesis / Q000187:drug effects; D007274:Injections, Intraperitoneal; D007700:Kinetics; D007970:Leukopenia / Q000139:chemically induced / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D011828:Radiation Chimera; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003520:Cyclophosphamide