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PMID: 6877240 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Enhancement of methotrexate resistance and dihydrofolate reductase gene amplification by treatment of mouse 3T6 cells with hydroxyurea.

Molecular and cellular biology ·Vol. 3 ·No. 6 ·1983-06-00 ·Pages 1097-107

Brown PC, Tlsty TD, Schimke RT

Abstract

We investigated various parameters associated with the initial selection of mouse 3T6 cells for resistance to single concentrations of methotrexate and characterized resistant colonies for the presence of additional (amplified) copies of the dihydrofolate reductase gene. Our results indicate that the frequency of occurrence of dihydrofolate reductase gene amplification varies with the selecting concentration of methotrexate and is highly variable between clonally derived sublines of mouse 3T6 cells. Second, we increased the frequency of occurrence of cells with amplified dihydrofolate reductase genes by transiently inhibiting DNA synthesis with hydroxyurea before the selection of cells in single concentrations of methotrexate. This effect was dependent on the concentration of hydroxyurea, the time of exposure to the drug, and the time interval between the removal of hydroxyurea and the selection of cells in methotrexate.

MeSH Terms
Animals Cell Line DNA Replication/drug effects Drug Resistance Gene Amplification/drug effects Hydroxyurea/pharmacology Methotrexate/pharmacology Mice Tetrahydrofolate Dehydrogenase/genetics
Chemicals
Tetrahydrofolate Dehydrogenase Hydroxyurea Methotrexate
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Brown P C
Tlsty T D
Schimke R T
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44 references, click to expand
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/mcb.3.6.1097-1107.1983
Published
1983-06-00
Pages
1097-107
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC368639
Subset
IM
Grants
NCI NIH HHS · CA 16318 · United States
NIGMS NIH HHS · GM 14931 · United States
External Links
PubMed source DOI: 10.1128/mcb.3.6.1097-1107.1983 PMC Full Text View journal details
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