Transfer of the cytidine deaminase cDNA into hematopoietic cells

被引：20

作者：

Flasshove, M ^{[1
]}

Frings, W ^{[1
]}

Schröder, JK ^{[1
]}

Moritz, T ^{[1
]}

Schütte, J ^{[1
]}

Seeber, S ^{[1
]}

机构：

[1] Univ Essen Gesamthsch, Sch Med, W German Canc Ctr, Dept Internal Med Canc Res, D-45122 Essen, Germany

来源：

LEUKEMIA RESEARCH | 1999年 / 23卷 / 11期

关键词：

drug resistance; gene therapy; cytidine deaminase; retroviral vector; hematopoiesis; cytosine arabinoside;

D O I：

10.1016/S0145-2126(99)00128-9

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

In order to investigate whether transfer of the cytidine deaminase (CDD) cDNA would increase chemotherapy resistance to cytosine arabinoside (ara-C) we used a retroviral vector expressing both, neomycin phosphotransferase and the CDD cDNA, to transduce hematopoietic cells from cell lines and from murine bone marrow (BM). After coculture on producer clones with a viral titer of 1 x 10(5) CFU/ml and up to 3-fold increased CDD enzymatic activity, WEHI-3 cell line and primary hematopoietic cells were exposed to ara-C in clonogenic assays. A transduction efficiency of 34.8 +/- 6.2% could be determined for BM clonogenic progenitor cells by G418 resistance. We could observe significantly more colonies (77 +/- 3.1%) surviving from transduced primary BM cells than from mock cells (51.7 +/- 9.3%) at 10(-8) mol/l ara-C, At 10(-7) mol/l ara-C 8.7% of BM cells became absolutely resistant after retroviral transduction. Our data confirm that CDD represents another candidate gene for increasing resistance to cytotoxic drugs in hematopoietic cells. (C) 1999 Elsevier Science Ltd. All rights reserved.

引用

页码：1047 / 1053

页数：7

共 41 条

[1] RETROVIRAL TRANSDUCTION AND EXPRESSION OF THE HUMAN ALKYLTRANSFERASE CDNA PROVIDES NITROSOUREA RESISTANCE TO HEMATOPOIETIC-CELLS [J].