Cyclophosphamide-induced enhancement of stem cell recovery from whole-body irradiation is radiation dose-dependent.
Although the enhancement of CFU-S recovery by CY pretreatment has been described for combinations of TBI greater than 4 Gy, no information exists as to whether such enhancement is operative at lower TBI doses (less than 3 Gy). B6D2F1 mice received intraperitoneal injections of CY (2 and 5 mg/mouse) at various time intervals prior to 2, 5 or 9 Gy TBI. The control group received the same dose of TBI without CY pretreatment. Six days after TBI, we determined the femoral content of CFU-S. Administration of 5 mg CY per mouse 3 days prior to 5 or 9 Gy TBI enhanced recovery of CFU-S with a substantial increase in CFU-S of 3- and 30-fold over control, respectively. In contrast, the administration of CY prior to 2 Gy TBI delayed recovery with CFU-S remaining at only 10 to 40% of control. This prolongation in CFU-S recovery was similar for CY doses of either 2 or 5 mg per mouse at all the time intervals tested (2, 3, 4 and 7 days prior to TBI). Our results demonstrate an enhancement of CFU-S recovery by pretreatment with CY for high doses of TBI that is reversed if the subsequent TBI dose is too low.
Pantel
K
K
Department of Internal Medicine, Wayne State University School of Medicine, Detriot, Michigan 48201.
Nakeff
A
A
D000818:Animals; D003114:Colony-Forming Units Assay; D003520:Cyclophosphamide / Q000494:pharmacology*; D004307:Dose-Response Relationship, Radiation; D004334:Drug Administration Schedule; D006410:Hematopoiesis / Q000187:drug effects / Q000528:radiation effects*; D006412:Hematopoietic Stem Cells / Q000528:radiation effects*; D051379:Mice; D011837:Radiation-Protective Agents; D013154:Spleen / Q000166:cytology; D014916:Whole-Body Irradiation
D011837:Radiation-Protective Agents; D003520:Cyclophosphamide