Transfection with a bcl-2 expression vector protects transplanted bone marrow from chemotherapy-induced myelosuppression.
The use of cytokines such as granulocyte-colony-stimulating factor (G-CSF) to ameliorate chemotherapy-induced myelosuppression may not only stimulate the recovery of normal hematopoietic cells but may also enhance the proliferation of the tumor cells with functional receptors for these cytokines. In this study, we show that administration of recombinant human (rh) G-CSF decreased the in vitro and in vivo cytotoxic effects of Adriamycin or etoposide on L1210 murine leukemic cells with receptors for rhG-CSF. Transplantation of bone marrow cells expressing high levels of bcl-2 from a retroviral construct [MPZenNeo(bcl-2)] (bcl-2-BMT) did not decrease the in vivo cytotoxic effect of etoposide on L1210 cells, but enabled recovery of myelopoiesis following etoposide-induced myelosuppression to almost the same extent as did the administration of rhG-CSF. These findings suggest the possibility that bcl-2 transfection could be used to protect transplanted bone marrow from chemotherapy-induced myelosuppression on behalf of administration of rhG-CSF, in case of treatment of tumors with functional receptors for rhG-CSF.
Kondo
S
S
Department of Neurosurgery, National Utano Hospital, Kyoto, Japan.
Yin
D
D
Morimura
T
T
Oda
Y
Y
Kikuchi
H
H
Takeuchi
J
J
D000818:Animals; D000970:Antineoplastic Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D001853:Bone Marrow / Q000187:drug effects* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004347:Drug Interactions; D005047:Etoposide / Q000037:antagonists & inhibitors / Q000494:pharmacology; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D007939:Leukemia L1210 / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D007958:Leukocyte Count / Q000187:drug effects; D051379:Mice; D009504:Neutrophils / Q000187:drug effects; D011519:Proto-Oncogenes; D011994:Recombinant Proteins / Q000494:pharmacology; D014162:Transfection / Q000235:genetics* / Q000379:methods
D000970:Antineoplastic Agents; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D005047:Etoposide; D004317:Doxorubicin