These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Increased resistance to nitrogen mustards and antifolates following in vitro selection of murine fibroblasts and primary hematopoietic cells transduced with a bicistronic retroviral vector expressing the rat glutathione S-transferase A3 and a mutant dihydrofolate reductase.
    Author: Belzile JP, Karatzas A, Shiu HY, Létourneau S, Palerme JS, Cournoyer D.
    Journal: Cancer Gene Ther; 2003 Aug; 10(8):637-46. PubMed ID: 12872145.
    Abstract:
    We have constructed a retroviral bicistronic vector, MFG/GID, that transduces the expression of both the A3 isoform of the rat glutathione S-transferase (GST A3), and the tyr-22 variant of the human dihydrofolate reductase (DHFR(L22Y)). Transduction of murine 3T3 fibroblasts with this vector increased their in vitro resistance to chlorambucil (1.8-fold) and trimetrexate (TMTX) (748-fold). TMTX selection of a mixed population of 20% GID-transduced NIH 3T3 cells and 80% control cells resulted in a marked increase in the GST peroxidase activity associated with the GST A3 isoform (17.7-fold). MFG/GID-transduced primary clonogenic murine hematopoietic progenitor cells were likewise more resistant to TMTX and chlorambucil than control beta-gal-transduced cells. Selecting GID-transduced hematopoietic cells with a combination of TMTX and a nucleoside transport inhibitor resulted in a marked increase in resistance upon re-exposure to TMTX (99% survival). Similarly, GID-transduced hematopoietic cells selected with TMTX were more resistant to chlorambucil, with 40% survival at a drug concentration that killed practically all control cells. These results suggest that antifolate-mediated selection of MFG/GID-transduced hematopoietic cells could be used as a mean to enrich the population of transduced cells prior to or following transplantation, thus potentially conferring in vivo chemoprotection to nitrogen mustards and antifolates.
    [Abstract] [Full Text] [Related] [New Search]