title: Methotrexate-resistant mechanisms in human choriocarcinoma cells.
abstract: Choriocarcinoma cells grown in the presence of methotrexate (MTX) developed resistance in two ways. HCCM-derived sublines (relatively high MTX resistance) produced enhanced levels of dihydrofolate reductase (DHFR) and had impaired transport of MTX. Altered transport was the primary determinant of response in CC1-derived sublines (low MTX resistance). Since the selection procedures used were identical, it was assumed that altered MTX transport was insufficient to account entirely for the various degrees of resistance. An increased level of DHFR activity was necessary for the development of high MTX resistance. The overproduction of DHFR was the consequence of amplification of the DHFR gene sequence. The incidence of double minutes (DMs) in metaphase paralleled the degree of resistance. However, DMs were also present in cells not showing DHFR gene amplification. Mechanisms other than DHFR gene multiplication were responsible for the de novo synthesis of DMs.
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Hokkaido University, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Sakai
authors.forename: N
authors.initials: N
authors.lastname: Wake
authors.forename: T
authors.initials: T
authors.lastname: Fujino
authors.forename: T
authors.initials: T
authors.lastname: Yasuda
authors.forename: H
authors.initials: H
authors.lastname: Kato
authors.forename: S
authors.initials: S
authors.lastname: Fujimoto
authors.forename: K
authors.initials: K
authors.lastname: Fujinaga
mesh_terms: D015139:Blotting, Southern; D002822:Choriocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002869:Chromosome Aberrations; D004351:Drug Resistance; D005260:Female; D006801:Humans; D008727:Methotrexate / Q000493:pharmacokinetics / Q000494:pharmacology*; D013762:Tetrahydrofolate Dehydrogenase / Q000032:analysis / Q000235:genetics; D014407:Tumor Cells, Cultured; D014594:Uterine Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D013762:Tetrahydrofolate Dehydrogenase; D008727:Methotrexate