title: Cell-cycle, phase-specific cell killing by carmustine in sensitive and resistant cells.
abstract: Cell-cycle, phase-specific cell kill caused by carmustine (BCNU) was measured in 4 cell lines with different sensitivities to the drug. Cells were treated with BCNU for 1 hour after which enriched subpopulations in various phases of the cell cycle were obtained by centrifugal elutriation and were assayed for cell survival. Levels of activity of guanine O6-alkyltransferase were measured for each line; intracellular levels of this repair protein have been correlated with cellular resistance to chloroethylnitrosoureas. Only BTRC-19, a clone of the 9L line, had significant levels of alkyltransferase activity and exhibited a relatively flat age-response curve to BCNU. Alkyltransferase activity was not detected in the other 3 cell lines, all of which displayed a similar age response in which G1- and G2/M-phase cells were relatively sensitive to BCNU compared with the response of S-phase cells. We conclude that alkyltransferase activity may overwhelm other determinants that cause cell-cycle phase specificity to BCNU.
authors.affiliation: Department of Neurological Surgery, University of California, San Francisco 94143-0520.
authors.forename: P A
authors.initials: PA
authors.lastname: Linfoot
authors.forename: M H
authors.initials: MH
authors.lastname: Barcellos-Hoff
authors.forename: T P
authors.initials: TP
authors.lastname: Brent
authors.forename: L J
authors.initials: LJ
authors.lastname: Marton
authors.forename: D F
authors.initials: DF
authors.lastname: Deen
mesh_terms: D000818:Animals; D002330:Carmustine / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects*; D002478:Cells, Cultured; D004260:DNA Repair; D004351:Drug Resistance; D008780:Methyltransferases / Q000032:analysis; D019853:O(6)-Methylguanine-DNA Methyltransferase; D051381:Rats
chemical_list: D008780:Methyltransferases; D019853:O(6)-Methylguanine-DNA Methyltransferase; D002330:Carmustine