Delayed effects of long-term administration of granulocyte colony-stimulating factor to mice.
We studied the effects of chronic administration of granulocyte colony-stimulating factor in nonmobilizing doses to mice. Over 18 months of the study, 55% animals of the treatment group died of unknown cause, blood diseases and tumors were found in 20% mice, and in 5% animals pathological changes were absent. Control mice had no diseases (normal values of total and differential leukocyte count). The diagnoses made over the first 7 months mainly included myeloproliferative diseases. Solid tumors were found at later terms. Suppurative inflammation at the site of injection was observed in all mice after 3-month treatment with granulocyte colony-stimulating factor. Our results indicate that chronic administration of granulocyte colony-stimulating factor in low doses leads to the development of etiologically different tumors and sharply reduced animal life span. The use of granulocyte colony-stimulating factor during allogeneic transplantation of hemopoietic stem cells can be hazardous for donors.
Nifontova
I N
IN
Department of Bone Marrow Transplantation, Laboratory for Physiology of Hemopoiesis, Research Center for Hemology, Russian Academy of Medical Sciences, Moscow.
Svinareva
D A
DA
Chertkov
I L
IL
Drize
N I
NI
Savchenko
V G
VG
D000818:Animals; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage* / Q000009:adverse effects*; D019650:Hematopoietic Stem Cell Mobilization / Q000009:adverse effects; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007958:Leukocyte Count; D008136:Longevity / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D009196:Myeloproliferative Disorders / Q000139:chemically induced; D009369:Neoplasms / Q000139:chemically induced; D011994:Recombinant Proteins; D013997:Time Factors; D014019:Tissue Donors; D014184:Transplantation, Homologous
D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D000069585:Filgrastim