Purine salvage rescue by xanthine-guanine phosphoribosyltransferase (XGPRT) potentiates methotrexate resistance conferred by transfer of a mutated dihydrofolate reductase gene Journal Article
| Authors: | Mineishi, S.; Nakahara, S.; Takebe, N.; Zhao, S. C.; Banerjee, D.; Bertino, J. R. |
| Article Title: | Purine salvage rescue by xanthine-guanine phosphoribosyltransferase (XGPRT) potentiates methotrexate resistance conferred by transfer of a mutated dihydrofolate reductase gene |
| 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. |
| Keywords: | genetics; methotrexate; mouse; animal; metabolism; animals; mice; bone marrow cells; antimetabolites, antineoplastic; drug resistance; drug resistance, neoplasm; mice, inbred c57bl; gene transfer; c57bl mouse; gene vector; genetic vectors; nucleotide sequence; gene therapy; base sequence; purines; purine derivative; bone marrow cell; dna primers; primer dna; dihydrofolate reductase; tetrahydrofolate dehydrogenase; antineoplastic antimetabolite; blotting, northern; cell strain 3t3; tioguanine; retrovirus; retroviridae; 3t3 cells; northern blotting; gene transfer techniques; pentosyltransferases; glycosyltransferase; male; article; xanthine phosphoribosyltransferase; thioguanine; dhfr; xgprt |
| Journal Title: | Cancer Gene Therapy |
| Volume: | 5 |
| Issue: | 3 |
| ISSN: | 0929-1903 |
| Publisher: | Nature Publishing Group |
| Date Published: | 1998-05-01 |
| Start Page: | 144 |
| End Page: | 149 |
| Language: | English |
| PUBMED: | 9622097 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 12 December 2016 -- Source: Scopus |
