Accelerated bone marrow recovery from radiation damage in etoposide-pretreated mice.
OBJECTIVE
Etoposide inhibits the activity of Topoisomerase II, and possesses radiosensitizing effects on cultured cells. We showed that pretreatment of mice with etoposide 1 day before whole-body irradiation (WBI) had a protective effect against radiation-induced bone marrow death. The number of endogenous colony-forming units (CFU-S) surviving in WBI mice was significantly increased by pretreatment with etoposide. The purpose of the present study is to clarify mechanisms underlying the protective activity of etoposide against radiation-induced bone marrow damage.


METHODS
The spleen colony-forming cells (CFU-S) of femoral marrow were assayed by the method of Till and McCulloch. The proliferative state of CFU-S was assessed using the technique of Hodgson. The reduction in exogenous CFU-S after hydroxyurea injection was used to determine the fraction size of S-phase in CFU-S.


RESULTS
Etoposide pretreatment did not modify the cell survival parameters of exogeneous CFU-S when bone marrow cells were assayed immediately after WBI. Recovery of CFU-S in femoral marrow started earlier in mice receiving etoposide pretreatment than in the radiation alone group. Administration of hydroxyurea revealed that the accelerated recovery of CFU-S was due to an increased population of S phase cells, suggesting etoposide pretreatment shortened generation time of CFU-S.


CONCLUSIONS
The mechanism for the radioprotection appears to be accelerated proliferation of survived bone marrow cells rather than a change in cellular sensitivity to radiation.
Yamada
S
S
Division of Clinical Research and Radiation Health, National Institute of Radiological Sciences, Chiba, Japan.
Ando
K
K
Koike
S
S
Isono
K
K
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000528:radiation effects*; D002450:Cell Communication; D005047:Etoposide / Q000494:pharmacology*; D005260:Female; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000528:radiation effects; D051379:Mice; D008809:Mice, Inbred C3H; D008813:Mice, Inbred ICR; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D014916:Whole-Body Irradiation
D011837:Radiation-Protective Agents; D005047:Etoposide