| Popis: |
Gene amplification has been recently shown to play a pivotal role in the development of resistance to the folate analogue, methotrexate (MTX), in several cell culture systems (Schimke et al. 1978). Stepwise increases in the concentration of MTX supplied to the medium in which the murine lymphoblastoid line L5178Y was cultivated resulted in the development of 100,000-fold elevation in resistance (Dolnick et al. 1979). The resistant line, L5178YR, was able to grow in the presence of millimolar concentrations of MTX, and it was shown that these cells had a 300-fold elevation in the activity of the target enzyme, dihydrofolate reductase (DHFR). Moreover, the increase in DHFR activity could be correlated with a proportional increase in DHFR-specific mRNA (300-fold) as well as a 300 fold-increase in DHFR gene copies. |
