Loss and stabilization of amplified dihydrofolate reductase genes in mouse sarcoma S-180 cell lines

Journal Article · Tue Dec 01 04:00:00 EST 1981 · Mol. Cell. Biol.; (United States)

DOI:https://doi.org/10.1128/MCB.1.12.1084· OSTI ID:5996231

Kaufman, R J; Brown, P C; Schimke, R T

The authors studied the loss and stabilization of dihydrofolate reductase genes in clones of a methotrexate-resistant murine S-180 cell line. These cells contained multiple copies of the dihydrofolate reductase gene which were associated with double minute chromosomes. The growth rate of these cells in the absence of methotrexate was inversely related to the degree of gene amplification (number of double minute chromosomes). Cells could both gain and lose genes as a result of an unequal distribution of double minute chromosomes into daughter cells at mitosis. The loss of amplified dihydrofolate reductase genes during growth in the absence of methotrexate resulted from the continual generation of cells containing lower numbers of double minute chromosomes. Because of the growth advantage of these cells, they became dominant in the population. They also studied an unstably resistant S-180 cell line (clone) that, after 3 years of continuous growth in methotrexate, generated cells containing stably amplified dihydrofolate reductase genes. These genes were present on one or more chromosomes, and they were retained in a stable state.

• Research Organization: Dept. of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139
• OSTI ID: 5996231
• Journal Information: Mol. Cell. Biol.; (United States), Journal Name: Mol. Cell. Biol.; (United States) Vol. 1:12; ISSN MCEBD
• Country of Publication: United States
• Language: English

Related Subjects

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560300 -- Chemicals Metabolism & Toxicology
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AMINO ACIDS
ANIMALS
ANTIMETABOLITES
AROMATICS
AZAARENES
CARBOXYLIC ACIDS
CELL CULTURES
CELL DIVISION
CHROMOSOME LOSSES
CLONE CELLS
CLONING
CULTURE MEDIA
DISEASES
DNA-CLONING
DRUGS
ENZYMES
FOLIC ACID
GENE AMPLIFICATION
GENES
HEMATINICS
HEMATOLOGIC AGENTS
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
LOSSES
MAMMALS
METABOLISM
METHOTREXATE
MICE
MITOSIS
MUTAGENESIS
NEOPLASMS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
OXIDOREDUCTASES
PTERIDINES
RODENTS
SARCOMAS
SENSITIVITY
TOXICITY
VERTEBRATES
VITAMIN B GROUP
VITAMINS