PMID- 3677020
OWN - NLM
STAT- MEDLINE
DCOM- 19880104
LR  - 20190619
IS  - 0008-543X (Print)
IS  - 0008-543X (Linking)
VI  - 60
IP  - 12
DP  - 1987 Dec 15
TI  - The effect of tumor necrosis factor on normal human hematopoietic progenitors.
PG  - 2965-70
AB  - Tumor necrosis factor-alpha (TNF-alpha), a product of activated macrophages that 
      is cytotoxic to tumor cells, could be used to purge tumor cells from bone marrow 
      before autologous bone marrow transplantation for hematologic malignancies and/or 
      solid tumors. To determine whether exposure to TNF-alpha would have an inhibitory 
      effect on hematopoietic progenitors, we incubated normal human bone marrow with a 
      wide range of concentrations of recombinant human TNF. In order to mimic the 
      conditions that would be used in bone marrow purging, bone marrow cell 
      suspensions were incubated with TNF in doses ranging from 500 to 100,000 U/ml for 
      24 hours, and were assayed for colony formation in agar. We noted a 
      dose-dependent inhibition of total colony-forming units (CFU) at days 7 and 14, 
      with 50% inhibition occurring at 60,000 U/ml of TNF. TNF exerted a differential 
      effect on CFU so that colony formation by erythroid (CFU-E), multipotential 
      (CFU-GEMM), and macrophage (CFU-M) progenitors was suppressed to a greater extent 
      than that by granulocyte progenitors (CFU-G). However, even after preincubation 
      with TNF at high doses such as 100,000 U/ml, the inhibitory effects of TNF could 
      be abolished by washing cells before culturing. This study demonstrates that 
      hematopoietic precursors survive treatment with TNF at doses that have been shown 
      to be cytotoxic to tumor cells. Although TNF has a significant inhibitory effect 
      on the growth of erythroid, multipotential, and macrophage progenitors in vitro, 
      this effect depends on continuous exposure to TNF for more than 24 hours. Thus, 
      TNF may be useful as a bone marrow purging agent against tumor cells, with 
      relative sparing of normal marrow elements.
FAU - Abboud, S L
AU  - Abboud SL
AD  - Department of Pathology, VA Medical Center, Cleveland, OH 44106.
FAU - Gerson, S L
AU  - Gerson SL
FAU - Berger, N A
AU  - Berger NA
LA  - eng
GR  - CA 24986/CA/NCI NIH HHS/United States
GR  - ESCAK11-00134/ES/NIEHS NIH HHS/United States
GR  - GM 26463/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Cancer
JT  - Cancer
JID - 0374236
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Colony-Forming Units Assay
MH  - Hematopoietic Stem Cells/*drug effects
MH  - Humans
MH  - In Vitro Techniques
MH  - Tumor Necrosis Factor-alpha/*pharmacology
EDAT- 1987/12/15 00:00
MHDA- 1987/12/15 00:01
CRDT- 1987/12/15 00:00
PHST- 1987/12/15 00:00 [pubmed]
PHST- 1987/12/15 00:01 [medline]
PHST- 1987/12/15 00:00 [entrez]
AID - 10.1002/1097-0142(19871215)60:12<2965::aid-cncr2820601219>3.0.co;2-o [doi]
PST - ppublish
SO  - Cancer. 1987 Dec 15;60(12):2965-70. doi: 
      10.1002/1097-0142(19871215)60:12<2965::aid-cncr2820601219>3.0.co;2-o.