PMID: 8449831Jan 1, 1993Paper

Differential alterations of dihydrofolate reductase gene in human leukemia cell lines made resistant to various folate analogues

Japanese Journal of Cancer Research : Gann
H MiyachiY Ando

Abstract

In order to clarify a molecular mechanism of folate resistance in leukemia cells, we studied alterations of the dihydrofolate reductase (DHFR) gene in a human leukemia cell line, MOLT-3, and its sublines made resistant to methotrexate (MTX), trimetrexate (TMQ) and N10-propargyl-5,8-dideazafolic acid (CB3717), alone or in combination. Major alterations of the DHFR gene were examined by Southern analysis of high-molecular-weight DNA. The presence of a base change (T-->C) at nucleotide position 91 of the DHFR gene, which is reported to be responsible for the reduced affinity of the enzyme for MTX in an MTX-resistant human colon carcinoma cell, was examined by allele-specific oligonucleotide hybridization. In a 10,000-fold MTX-resistant subline (MOLT-3/MTX10,000), the normal allele of DHFR gene had been amplified. In contrast, a 200-fold TMQ-resistant subline (MOLT-3/TMQ200) and a 30-fold CB3717-resistant subline selected from MOLT-3/TMQ200 (MOLT-3/TMQ200-CB-3717(30)) were shown to have the mutant allele. Furthermore, the mutant allele had been amplified in a 500-fold MTX-resistant subline, which was established by the continuous exposure of the MOLT-3/TMQ200 cells to stepwise increases of drug concentration and designated as MOLT-...Continue Reading

References

Jan 1, 1991·Cancer Chemotherapy and Pharmacology·Y TakemuraT Ohnuma
Nov 3, 1983·The New England Journal of Medicine·J JolivetB A Chabner
Jan 1, 1981·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·T R JonesK R Harrap
May 1, 1980·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·A H CalvertK R Harrap

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