PMID- 10954901
OWN - NLM
STAT- MEDLINE
DCOM- 20001010
LR  - 20131121
IS  - 1043-0342 (Print)
IS  - 1043-0342 (Linking)
VI  - 11
IP  - 12
DP  - 2000 Aug 10
TI  - GST-pi gene-transduced hematopoietic progenitor cell transplantation overcomes 
      the bone marrow toxicity of cyclophosphamide in mice.
PG  - 1671-81
AB  - Autologous transplantation of bone marrow cells (BMCs) transduced with the 
      multidrug resistance 1 (MDR1) gene or dihydrofolate reductase (DHFR) gene has 
      already been applied in clinical chemoprotection trials. However, anticancer 
      drugs frequently used in high-dose chemotherapy (HDC), such as alkylating agents, 
      are not relevant to MDR1 or DHFR gene products. In this context, we have 
      previously reported that glutathione S-transferase-pi (GST-pi) gene-transduced 
      human CD34(+) cells showed resistance in vitro against 
      4-hydroperoxicyclophosphamide, an active form of cyclophosphamide (CY). In the 
      present study, a subsequent attempt was made in a murine model to evaluate the 
      effectiveness of transplantation of GST-pi-transduced BMCs to protect bone marrow 
      against high-dose CY. The gene transfection was carried out retrovirally, 
      employing a recombinant fibronectin fragment. Transfection efficiency into CFU-GM 
      was 30%. After the transplantation, recipient mice (GST-pi mice) received three 
      sequential courses of high-dose CY. As the chemotherapy courses advanced, both 
      shortening of recovery period from WBC nadir and shallowing of WBC nadir were 
      observed. In contrast to the fact that three of seven control mice died, possibly 
      due to chemotoxicity, all seven GST-pi mice were alive after the third course, at 
      which point the vector GST-pi gene was detected in 50% of CFU-GM derived from 
      their BMCs and peripheral blood mononuclear cells. When BMCs obtained from these 
      seven mice were retransplanted into secondary recipient mice, 20% of CFU-GM from 
      BMCs showed positive signals for vector GST-pi DNA after 6 months. These data 
      indicate that the GST-pi gene can confer resistance to bone marrow against CY by 
      being transduced into long-term repopulating cells.
FAU - Matsunaga, T
AU  - Matsunaga T
AD  - Fourth Department of Internal Medicine, Sapporo Medical University School of 
      Medicine, Japan.
FAU - Sakamaki, S
AU  - Sakamaki S
FAU - Kuga, T
AU  - Kuga T
FAU - Kuroda, H
AU  - Kuroda H
FAU - Kusakabe, T
AU  - Kusakabe T
FAU - Akiyama, T
AU  - Akiyama T
FAU - Konuma, Y
AU  - Konuma Y
FAU - Hirayama, Y
AU  - Hirayama Y
FAU - Kobune, M
AU  - Kobune M
FAU - Kato, J
AU  - Kato J
FAU - Sasaki, K
AU  - Sasaki K
FAU - Kogawa, K
AU  - Kogawa K
FAU - Koyama, R
AU  - Koyama R
FAU - Niitsu, Y
AU  - Niitsu Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Hum Gene Ther
JT  - Human gene therapy
JID - 9008950
RN  - 0 (Antineoplastic Agents, Alkylating)
RN  - 0 (Isoenzymes)
RN  - 8N3DW7272P (Cyclophosphamide)
RN  - EC 2.5.1.18 (GSTP1 protein, human)
RN  - EC 2.5.1.18 (Glutathione S-Transferase pi)
RN  - EC 2.5.1.18 (Glutathione Transferase)
RN  - EC 2.5.1.18 (Gstp1 protein, mouse)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents, Alkylating/*toxicity
MH  - Bone Marrow/*drug effects
MH  - Cyclophosphamide/*toxicity
MH  - Female
MH  - *Gene Transfer Techniques
MH  - Glutathione S-Transferase pi
MH  - Glutathione Transferase/*genetics/metabolism
MH  - *Hematopoietic Stem Cell Transplantation
MH  - Hematopoietic Stem Cells/*drug effects
MH  - Humans
MH  - Isoenzymes/*genetics/metabolism
MH  - Leukocyte Count
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Polymerase Chain Reaction
EDAT- 2000/08/24 11:00
MHDA- 2000/10/14 11:01
CRDT- 2000/08/24 11:00
PHST- 2000/08/24 11:00 [pubmed]
PHST- 2000/10/14 11:01 [medline]
PHST- 2000/08/24 11:00 [entrez]
AID - 10.1089/10430340050111322 [doi]
PST - ppublish
SO  - Hum Gene Ther. 2000 Aug 10;11(12):1671-81. doi: 10.1089/10430340050111322.