Stem cell factor enhances the survival of murine intestinal stem cells after photon irradiation.
Recombinant rat stem cell factor (SCF) has been shown to decrease lethality in mice exposed to total-body irradiation (TBI) in the lower range of lethality through radioprotection of hematopoietic stem cells and acceleration of bone marrow repopulation. This study evaluates the effect of SCF on the survival of the intestinal mucosal stem cell after TBI. This non-hematopoietic stem cell is clinically relevant. Gastrointestinal toxicity is common during and after abdominal and pelvic radiation therapy and limits the radiation dose in these regions. As observed with bone marrow, the administration of SCF to mice prior to TBI enhanced the survival of mouse duodenal crypt stem cells. The maximum enhancement of survival was seen when 100 micrograms/kg of SCF was given intraperitoneally 8 h before irradiation. This regimen increased the survival of duodenal crypt stem cells after 12.0 Gy TBI from 22.5 +/- 0.7 per duodenal cross section for controls to 30.0 +/- 1.7 after treatment with SCF (P = 0.03). The TBI dose producing 50% mortality at 6 days (LD50/6) was increased from 14.9 Gy for control mice to 19.0 Gy for mice treated with SCF (dose modification factor = 1.28). These findings demonstrate that SCF has radioprotective effects on a non-hematopoietic stem cell population and suggest that SCF may be of clinical value in preventing radiation injury to the intestine.
Leigh
B R
BR
Department of Radiation Oncology, Stanford University Hospital, California 94305.
Khan
W
W
Hancock
S L
SL
Knox
S J
SJ
D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology*; D007422:Intestines / Q000528:radiation effects*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D017785:Photons; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D019089:Stem Cell Factor; D013234:Stem Cells / Q000187:drug effects / Q000528:radiation effects*
D016298:Hematopoietic Cell Growth Factors; D011837:Radiation-Protective Agents; D019089:Stem Cell Factor