Purine salvage rescue by xanthine-guanine phosphoribosyltransferase (XGPRT) potentiates methotrexate resistance conferred by transfer of a mutated dihydrofolate reductase gene

Shin Mineishi, Saori Nakahara, Naoka Takebe, Shi Cheng Zhao, Debabrata Banerjee, Joseph R. Bertino

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

We have previously shown that successful gene transfer of a mutated dihydrofolate reductase (DHFR) cDNA confers resistance to methotrexate (MTX) upon infected cells. We constructed a retrovirus vector, DC/SV6S31GPT, which carries both the Escherichia coli xanthine-guanine phosphoribosyltransferase gene and the mutated Serine 31 DHFR gene. Mouse fibroblast NIH3T3 cells infected with DC/SV6S31GPT are more resistant to MTX than cells infected with DC/SV6S31, which carries the Serine 31 DHFR and the neomycin resistance gene cDNA. The mechanism of this augmented resistance is the increased salvaging of purines due to expression of xanthine-guanine phosphoribosyltransferase, as the augmentation does not occur when dialyzed serum, containing little xanthine or guanine, is used for cytotoxicity assays. These results indicate that coexpression of a metabolically related gene can potentiate the resistance carried by a drug resistance gene. This vector may be useful in clinical gene therapy to protect bone marrow from the toxic effects of MTX.

Original languageEnglish (US)
Pages (from-to)144-149
Number of pages6
JournalCancer Gene Therapy
Volume5
Issue number3
StatePublished - Dec 1 1998

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Tetrahydrofolate Dehydrogenase
Methotrexate
Genes
Serine
Complementary DNA
Purines
Xanthine
Neomycin
Poisons
Guanine
Retroviridae
Drug Resistance
Genetic Therapy
purine
xanthine phosphoribosyltransferase
Fibroblasts
Bone Marrow
Escherichia coli
Serum

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Molecular Biology
  • Cancer Research

Cite this

Mineishi, Shin ; Nakahara, Saori ; Takebe, Naoka ; Zhao, Shi Cheng ; Banerjee, Debabrata ; Bertino, Joseph R. / Purine salvage rescue by xanthine-guanine phosphoribosyltransferase (XGPRT) potentiates methotrexate resistance conferred by transfer of a mutated dihydrofolate reductase gene. In: Cancer Gene Therapy. 1998 ; Vol. 5, No. 3. pp. 144-149.
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abstract = "We have previously shown that successful gene transfer of a mutated dihydrofolate reductase (DHFR) cDNA confers resistance to methotrexate (MTX) upon infected cells. We constructed a retrovirus vector, DC/SV6S31GPT, which carries both the Escherichia coli xanthine-guanine phosphoribosyltransferase gene and the mutated Serine 31 DHFR gene. Mouse fibroblast NIH3T3 cells infected with DC/SV6S31GPT are more resistant to MTX than cells infected with DC/SV6S31, which carries the Serine 31 DHFR and the neomycin resistance gene cDNA. The mechanism of this augmented resistance is the increased salvaging of purines due to expression of xanthine-guanine phosphoribosyltransferase, as the augmentation does not occur when dialyzed serum, containing little xanthine or guanine, is used for cytotoxicity assays. These results indicate that coexpression of a metabolically related gene can potentiate the resistance carried by a drug resistance gene. This vector may be useful in clinical gene therapy to protect bone marrow from the toxic effects of MTX.",
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Purine salvage rescue by xanthine-guanine phosphoribosyltransferase (XGPRT) potentiates methotrexate resistance conferred by transfer of a mutated dihydrofolate reductase gene. / Mineishi, Shin; Nakahara, Saori; Takebe, Naoka; Zhao, Shi Cheng; Banerjee, Debabrata; Bertino, Joseph R.

In: Cancer Gene Therapy, Vol. 5, No. 3, 01.12.1998, p. 144-149.

Research output: Contribution to journalArticle

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