Gene Amplification in Mammalian Cells after Exposure to Ionizing Radiation and UV
Since the initial observations (1, 2), gene amplifications have been detected in several organisms and cell cultures (review: 3). One system has been studied extensively: The development of resistance to methotrexate (MTX). This resistance is associated with the amplification of the gene for the methotrexate target enzyme, dihydrofolate reductase (4). In this system, the spontaneous rate of gene amplification has been determined to 10−3 events per cell division (5). Amplification is enhanced not only by MTX treatment but also by other agents which affect nucleotide metabolism (3), or by treatment of cells with tumor promoters or mutagens (6, 7). The amplification goes along with the appearance of unstable chromosomal structures called double minute chromosomes (8), or of stably integrated homogeneously staining regions (9).
KeywordsGene Amplification Alpha Particle Dihydrofolate Reductase Human Skin Fibroblast Ataxia Telangiectasia
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