Cell biology: Gene amplification and drug resistance

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Gene Amplification, Drug Resistance, and Cancer1

The finding that genetic alterations, i.e., mutations, can involve quantitative changes, as contrasted to the qualitative changes, in a genome was first made in Drosophila (88) and more recently has been examined extensively as a developmental process with ribosomal genes in amphibians (18; see Ref. 13 for review). The phenomenon of selective gene amplification in cultured mam malian cells was ...

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Gene amplification and drug resistance in cultured murine cells.

Resistance of mouse cells to the folate analog, methotrexate, results from selection of increasingly resistant cells on progressive increases of methotrexate in the culture medium. High-level resistance is associated with high rates of synthesis of dihydrofolate reductase and correspondingly high numbers of reductase genes. In some variants high resistance and gene copy number are stable in the...

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Frequency of Drug Resistance Gene Amplification in Clinical Leishmania Strains

Experimental studies about Leishmania resistance to metal and antifolates have pointed out that gene amplification is one of the main mechanisms of drug detoxification. Amplified genes code for adenosine triphosphate-dependent transporters (multidrug resistance and P-glycoproteins P), enzymes involved in trypanothione pathway, particularly gamma glutamyl cysteine synthase, and others involved i...

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Mathematical models of gene amplification with applications to cellular drug resistance and tumorigenicity.

An increased number of copies of specific genes may offer an advantage to cells when they grow in restrictive conditions such as in the presence of toxic drugs, or in a tumor. Three mathematical models of gene amplification and deamplification are proposed to describe the kinetics of unstable phenotypes of cells with amplified genes. The models differ in details but all assume probabilistic mec...

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Drug-Resistant Tuberculosis Transmission and Resistance Amplification within Families

Drug-resistant tuberculosis is caused by transmission of resistant strains of Mycobacterium tuberculosis and by acquisition of resistance through inadequate treatment. We investigated the clinical and molecular features of the disease in 2 families after drug-resistant tuberculosis was identified in 2 children. The findings demonstrate the potential for resistance to be transmitted and amplifie...

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ژورنال

عنوان ژورنال: Nature

سال: 1984

ISSN: 0028-0836,1476-4687

DOI: 10.1038/307212a0