Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2008-2-27
pubmed:abstractText
Tumor radiotherapy with large-field irradiation results in an increase in apoptosis of the radiosensitive hematopoietic stem cells (CD34(+)). The aim of this study was to demonstrate the radioprotective potential of MDR1 overexpression in human CD34(+) cells using a lentiviral self-inactivating vector. Transduced human undifferentiated CD34(+) cells were irradiated with 0-8 Gy and held in liquid culture under myeloid-specific maturation conditions. After 12 days, MDR1 expression was determined by the rhodamine efflux assay. The proportion of MDR1-positive cells in cells from four human donors increased with increasing radiation dose (up to a 14-fold increase at 8 Gy). Determination of expression of myeloid-specific surface marker proteins revealed that myeloid differentiation was not affected by transduction and MDR1 overexpression. Irradiation after myeloid differentiation also led to an increase of MDR1-positive cells with escalating radiation doses (e.g. 12.5-16% from 0-8 Gy). Most importantly, fractionated irradiation (3 x 2 Gy; 24-h intervals) of MDR1-transduced CD34(+) cells resulted in an increase in MDR1-positive cells (e.g. 3-8% from 0-3 x 2 Gy). Our results clearly support a radioprotective effect of lentiviral MDR1 overexpression in human CD34(+) cells. Thus enhancing repopulation by surviving stem cells may increase the radiation tolerance of the hematopoietic system, which will contribute to widening the therapeutic index in radiotherapy.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0033-7587
pubmed:author
pubmed:issnType
Print
pubmed:volume
169
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
301-10
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
MDR1 gene transfer using a lentiviral SIN vector confers radioprotection to human CD34+ hematopoietic progenitor cells.
pubmed:affiliation
Department of Radiation Oncology, Mannheim Medical Centre, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany. patrick.maier@radonk.ma.uni-heidelberg.de
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't