[Selective myelo-protection by MDR1 and MnSOD genes regulated by a specific promoter].
OBJECTIVE
To study the specific protection of myeloid cells from chemotherapeutic agents and radiation.


METHODS
The recombinant retroviral vectors containing MDR1 gene and MnSOD gene regulated by APN myeloid promoter were constructed and introduced into myeloblastic cell line KG1a and hepatoma cell line BEL7402. The resistance of the cells to antitumor drugs and radiation were analyzed by cell survival assay. In vivo, the murine bone marrow cells were isolated and infected by the retroviral particles, which were transplanted into recipient mouse treated with paclitaxel or X-ray. The murine white blood cell (WBC) was counted in order to assay the effects of MDR1 or MnSOD gene on hematopoiesis in the course of chemotherapy and radiotherapy.


RESULTS
The resistance to chemotherapeutic agents such as cochicine, Vp-16, vincristine, doxorubcin and paclitaxel were elevated markedly by 10.6, 10.4, 11.2, 4.2 and 14.2 folds in KG1a cell line transduced with MDR1 gene. The resistance to radiation increased 3.7 folds at the dose of 10 Gy compared with parental cells in KGla cell line transduced with MnSOD gene derived by APN promoter. In contrast, the chemosensitivity and the radiosensitivity showed no significant change in BEL 7402 cell line transduced with MDR1 gene and MnSOD gene. In vivo, the WBC counts in the mouse introduced with MDR1 gene or MnSOD gene were higher than those in the control mouse (P < 0.01).


CONCLUSIONS
The expression of MDR1 gene and MnSOD gene regulated by APN myeloid promoter is effective on myelo-specific protection without enhancing the resistance of tumor cells in vitro. The hematopoiesis can be reconstituted in vivo during anticancer drug or radiation treatment. This study may provide experimental evidence and new clues for myeloprotection of cancer patients being treated with chemotherapy and/or radiotherapy.
Liang
Li-bo
LB
Cancer Institute (Hospital), Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100021, China.
Ma
Ye-wei
YW
Zhou
Xiao-shan
XS
Yang
Jun
J
Li
Yan-chun
YC
Wang
Zheng
Z
Zhou
Lan-ping
LP
Zhang
Yang-pei
YP
Zhao
Qing-zheng
QZ
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001853:Bone Marrow / Q000187:drug effects / Q000502:physiology; D018826:CD13 Antigens / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects; D004347:Drug Interactions; D005047:Etoposide / Q000494:pharmacology; D005786:Gene Expression Regulation; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000235:genetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011401:Promoter Regions, Genetic; D020011:Protective Agents / Q000494:pharmacology*; D011837:Radiation-Protective Agents / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000235:genetics / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014750:Vincristine / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D020011:Protective Agents; D011837:Radiation-Protective Agents; D014750:Vincristine; D005047:Etoposide; D013482:Superoxide Dismutase; D018826:CD13 Antigens