Effects of recombinant transforming growth factor-beta 1 on hematologic recovery after treatment of mice with 5-fluorouracil.
Transforming growth factor beta 1 (TGF-beta 1) has been shown to inhibit bone marrow colony formation after in vitro treatment as well as after in vivo administration to normal mice. These data suggest that TGF-beta might either protect, or further depress, progenitor cell levels in mice exposed to a cell cycle-active drug such as 5-fluorouracil (5FU). rTGF-beta 1 was administered repeatedly by either the i.v. or i.p. routes to mice during the hyperproliferative state of the bone marrow that occurs 7 to 9 days after the i.v. administration of 150 mg/kg 5FU. The formation of both multilineage and the more differentiated (CFU-c) colonies was inhibited by 20 to 40%/culture, and 66 to 93%/mouse. When multiple doses of rTGF-beta 1 were administered systemically immediately before the injection of 5FU, the resulting rebound in the number of CFU-c and multilineage colonies containing granulocyte, erythroid, megakaryocyte, and macrophage lineage colonies per culture was markedly inhibited by 30 to 77%, whereas the total number of CFU per mouse was inhibited up to 93%. This effect was maximal when rTGF-beta 1 was administered at daily doses of greater than or equal to 5 micrograms/mouse for at least 3 days. This inhibition of the recovery of the bone marrow from 5FU treatment induced by rTGF-beta 1 was a delayed transient response because by day 16 the progenitor cell numbers and bone marrow cellularity were identical to the 5FU-treated marrow controls.
Jansen
R
R
Laboratory of Experimental Immunology, NCI-FCRDC, MD 21702-1201.
Damia
G
G
Usui
N
N
Keller
J
J
Futami
H
H
Goey
H
H
Back
T T
TT
Longo
D L
DL
Ruscetti
F W
FW
Wiltrout
R H
RH
D000818:Animals; D001853:Bone Marrow / Q000502:physiology; D003114:Colony-Forming Units Assay; D005472:Fluorouracil / Q000494:pharmacology*; D006410:Hematopoiesis / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D005472:Fluorouracil