SarCNU, a novel chloroethylnitrosourea analogue, is transported by the extraneuronal uptake2 transporter (uptake2). SK-MG-1 human glioma cells are sensitive to SarCNU cytotoxicity and express uptake 2 whereas SKI-1 glioma cells have no detectable transporter, and are relatively resistant. To clone uptake2, we detected differences in RNA expression utilizing differential display. With differential display, we detected a novel sequence expressed in SK-MG-1 cells but not in SKI-1 cells, having 62% homology to an expressed sequence tag clone from human brain, and could be a partial sequence of uptake2. In the treatment of SF-295 glioma xenografts in athymic mice, SarCNU had superior activity than 1,3-bis-(2-chloroethyl)-1-nitrosourea. This suggested that SF-295 cells express uptake2. We determined if expression of uptake2 in the established SF-295 cell line correlated with the enhanced activity of SarCNU in vivo. Transport of [3H]SarCNU was not decreased by inhibitors of uptake2 in the SF-295 cell line and its steady state accumulation was similar to that of SKI-1. The increased stability of SarCNU versus BCNU may account for its enhanced activity in vivo or the expression of uptake2 in vivo may differ from its expression in vitro.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.20273 |
| Date | January 1997 |
| Creators | Marcantonio, Daniela. |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Division of Experimental Medicine.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001604656, proquestno: MQ44217, Theses scanned by UMI/ProQuest. |
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