Concept explainers
Interpretation:
A mammalian cell line was cultured for many generations in the presence of methotrexate, whose concentration in the culture medium was steadily increased. After maximum resistance to methotrexate had been achieved, the cells were transferred to drug-free medium for many more generations. At the beginning of the experiment, dihydrofolate reductase represented 0.1% of the soluble protein in the cell; at maximum resistance it was 10.0% and at the conclusion of the experiment, 1.5%. The qualitative terms the processes involved in generating maximum resistance needs to be described.
Concept Introduction:
Dihydrofolate reductase (DHFR) is asalvage pathway enzyme encoded by MDR gene involved in synthesis of dinucleotides like dTTP, dATP, dGTP used in DNA synthesis. Methotrexate (MTX) is a drug that inhibits DHFR.
The qualitative terms associated with this process are decreased by the uptake of MTX by mammalian cells and DHFR gene amplification resulting in its increased production.
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Biochemistry: Concepts and Connections (2nd Edition)
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