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

Journal Article · Fri Jun 01 00:00:00 EDT 1984 · Mol. Cell. Biol.; (United States)

DOI:https://doi.org/10.1128/MCB.4.6.1050· OSTI ID:6133404

Tlsty, T D; Brown, P C; Schimke, R T

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.

• Research Organization: Stanford Univ., CA (United States)
• OSTI ID: 6133404
• Journal Information: Mol. Cell. Biol.; (United States), Vol. 4:6
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
FIBROBLASTS
BIOLOGICAL RADIATION EFFECTS
GENES
CONDENSED AROMATICS
METHOTREXATE
MICE
PHORBOL ESTERS
TUMOR PROMOTERS
ULTRAVIOLET RADIATION
ANIMAL CELLS
ANIMALS
ANTIMETABOLITES
AROMATICS
BIOLOGICAL EFFECTS
CARCINOGENS
CONNECTIVE TISSUE CELLS
DRUGS
ELECTROMAGNETIC RADIATION
ESTERS
MAMMALS
ORGANIC COMPOUNDS
PROMOTERS
RADIATION EFFECTS
RADIATIONS
RODENTS
SOMATIC CELLS
VERTEBRATES
550400* - Genetics