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PMID: 6738530 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

UV radiation facilitates methotrexate resistance and amplification of the dihydrofolate reductase gene in cultured 3T6 mouse cells.

Molecular and cellular biology ·Vol. 4 ·No. 6 ·1984-06-00 ·Pages 1050-6

Tlsty TD, Brown PC, Schimke RT

Abstract

Pretreatment of 3T6 murine cells with the carcinogen UV radiation or N-acetoxy-N-acetylaminofluorene increased the number of methotrexate-resistant colonies. This carcinogen-induced enhancement was seen only at low toxicities. The enhancement was transient and was observed at its maximum when cells were subjected to methotrexate selection 12 to 24 h after treatment. The addition of a tumor-promoting agent, 12-O-tetradecanoylphorbol-13-acetate, during or after carcinogen treatment further enhanced this effect. A large proportion of the resistant colonies had an increase in the dihydrofolate reductase gene copy number and the relative proportions of colonies with amplified genes were similar, regardless of whether selected cells were untreated, treated with carcinogen, or treated with carcinogen plus promoter. We discuss some of the variables which both enhance the generation and improve the detection of methotrexate-resistant colonies, as well as certain implications of our results for the generation and mechanism of gene amplification.

MeSH Terms
Acetoxyacetylaminofluorene/toxicity Animals Cells, Cultured DNA Replication/drug effects,radiation effects Dose-Response Relationship, Drug Drug Resistance Gene Amplification/drug effects,radiation effects Genes/drug effects,radiation effects Kinetics Methotrexate/toxicity Mice Tetradecanoylphorbol Acetate/toxicity Tetrahydrofolate Dehydrogenase/genetics Ultraviolet Rays
Chemicals
Acetoxyacetylaminofluorene Tetrahydrofolate Dehydrogenase Tetradecanoylphorbol Acetate Methotrexate
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Tlsty T D
Brown P C
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.4.6.1050-1056.1984
Published
1984-06-00
Pages
1050-6
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC368872
Subset
IM
Grants
NCI NIH HHS · CA 09302 · United States
NCI NIH HHS · CA 16318 · United States
External Links
PubMed source DOI: 10.1128/mcb.4.6.1050-1056.1984 PMC Full Text View journal details
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