Mechanism of methotrexate-sensitivity of choriocarcinoma cells in culture.
Four cell lines established from choriocarcinoma were compared for sensitivity to methotrexate (MTX). In this paper, we have compared the relative gene copy number of dihydrofolate reductase (DHFR), the target enzyme of methotrexate (MTX), in order to clarify whether or not amplification of the gene is involved in the relative resistance to MTX observed for one of the cell lines, designated NaUCC-1, which is 4- to 5-fold more resistant to MTX as compared with the other cell lines and exhibits a reduced uptake of [3H]MTX. Neither dot blot nor Southern blot hybridization revealed any significant difference in the gene copy number among the four cell lines. Therefore, the resistance to MTX of the NaUCC-1 line is explained by a reduced uptake of the drug, rather than amplification of the target gene.
Inoue
T
T
Department of Obstetrics and Gynecology, Nagoya University School of Medicine.
Nagura
E
E
Toyoda
T
T
Ishizuka
T
T
Gotoh
S
S
Kawashima
K
K
Tomoda
Y
Y
Nagai
Y
Y
D000818:Animals; D002460:Cell Line; D002822:Choriocarcinoma / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D004247:DNA; D004262:DNA Restriction Enzymes; D005784:Gene Amplification / Q000187:drug effects; D006801:Humans; D008727:Methotrexate / Q000494:pharmacology*; D051379:Mice; D008819:Mice, Nude; D009693:Nucleic Acid Hybridization; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism
D004247:DNA; D013762:Tetrahydrofolate Dehydrogenase; D004262:DNA Restriction Enzymes; D008727:Methotrexate