Cell-cycle, phase-specific cell killing by carmustine in sensitive and resistant cells.
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.
Linfoot
P A
PA
Department of Neurological Surgery, University of California, San Francisco 94143-0520.
Barcellos-Hoff
M H
MH
Brent
T P
TP
Marton
L J
LJ
Deen
D F
DF
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
D008780:Methyltransferases; D019853:O(6)-Methylguanine-DNA Methyltransferase; D002330:Carmustine