Membrane and cytoplasmic changes in 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU)-sensitive and resistant human malignant glioma-derived cell lines.
Human glioma-derived cell lines previously determined by a microtiter chemotherapy assay to be either 'sensitive' or 'resistant' to 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) were treated with BCNU (1-80 micrograms/ml) and observed using microcinematography, scanning electron microscopy, and transmission electron microscopy. Striking bleb formation and cell retraction were observed to occur in a dose-dependent relationship within minutes in the cells known to be BCNU-sensitive. At 15 micrograms/ml, 69% of cells showed blebs by 30 min, 87% by 90 min, and 100% by 4 hr. This activity was not seen in BCNU-resistant cells. These morphological changes occur at a time too early to be accounted for by the known BCNU mechanism of DNA alkylation and cross-link formation and suggest that cytoplasmic and/or membrane events may be significant initial events in the cytotoxic actions of BCNU.
D000328:Adult; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000648:ultrastructure; D002330:Carmustine / Q000494:pharmacology*; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects* / Q000648:ultrastructure; D003593:Cytoplasm / Q000187:drug effects* / Q000648:ultrastructure; D004351:Drug Resistance; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000648:ultrastructure; D006801:Humans; D008297:Male; D008855:Microscopy, Electron, Scanning; D008871:Microvilli / Q000187:drug effects / Q000648:ultrastructure; D008875:Middle Aged
D002330:Carmustine