[MTX resistant mechanisms in human choriocarcinoma cells].
Choriocarcinoma cells grown in the presence of MTX have developed resistance in two ways. The HCCM derived sublines (relatively high MTX resistant) produced enhanced levels of DHFR and had relatively unimpaired transport of MTX, though altered transport was the primary determinant of response in the CC1 derived sublines (low MTX resistant). Since the selection procedure used was identical, it was assumed that altered MTX transport was insufficient to account entirely for various degrees of resistance. Increased 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 DMs in metaphases paralleled the degree of resistance. Since DMs were also present in the cells not showing DHFR gene amplification, mechanisms other than DHFR gene multiplication were responsible for the de novo synthesis of DMs.
D002478:Cells, Cultured; D002822:Choriocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006063:Chorionic Gonadotropin / Q000378:metabolism; D004273:DNA, Neoplasm / Q000032:analysis; D004351:Drug Resistance; D005260:Female; D006801:Humans; D008727:Methotrexate / Q000378:metabolism / Q000494:pharmacology*; D011247:Pregnancy; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics / Q000378:metabolism; D014594:Uterine Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
D006063:Chorionic Gonadotropin; D004273:DNA, Neoplasm; D013762:Tetrahydrofolate Dehydrogenase; D008727:Methotrexate