Effect of human recombinant granulocyte colony-stimulating factor on
induction of myeloid leukemias by X-irradiation in mice
Y Kawase, M Akashi, H Ohtsu, Y Aoki, A Akanuma and G Suzuki
Division of Radiation Health, National Institute of Radiological Sciences,
Chiba, Japan.
Hematopoietic suppression is one of the serious problems induced by whole
body irradiation. Granulocyte colony-stimulating factor (G-CSF) stimulates
the progenitors of granulocytes and accelerates their recovery from bone
marrow suppression induced by cytotoxic chemotherapy or radiation. On the
other hand, G-CSF stimulates proliferation of myeloid leukemia cells as
well as normal granulocytes in vitro. We designed a method to determine if
G-CSF affects the incidence of myeloid leukemias induced by irradiation and
the types of leukemias induced according to the French-American-British
(FAB) classification in RFM/MsNrs mice. Administration of G-CSF (2
micrograms/d for 7 days) after a single 3-Gy irradiation significantly
increased the number of peripheral blood neutrophils as compared with those
in control mice. Even after discontinuation of G-CSF, both the total
leukocyte and neutrophil counts increased to day 10, and their levels
remained elevated until day 14. The incidence of myeloid leukemia in mice
exposed to a single 3-Gy irradiation was 18.6% (38 of 204), and treatment
with G-CSF did not increase the incidence (15.7% [32 of 204]). In the mice
with radiation-induced leukemia, those receiving G- CSF had a mean survival
time of 357 days, whereas those not receiving the factor survived for 349
days. There was no significant difference of survivals between the two
groups. Most of the radiation-induced leukemias in the two groups were M1
or M2, according to the FAB classification; no characteristic difference
was observed among the types of leukemias. Although G-CSF stimulated the
leukemia cells in vitro, G-CSF administration after irradiation did not
increase the occurrence of radiation-induced myeloid leukemias. Our results
show that administration of G-CSF effectively accelerates neutrophil
recovery from irradiation-induced hematopoietic injury and does not enhance
the induction of myeloid leukemia in RFM/MsNrs mice by irradiation.
Volume 82,
Issue 7,
pp. 2163-2168,
10/01/1993
Copyright © 1993 by The American Society of Hematology
