Biochemical evidence for two different mechanisms for bleomycin-induced cell killing.
Using pulsed-field gel electrophoresis, we have measured the ability of two bleomycin-sensitive mutants, XR-1 and BL-10, to repair DNA double-strands breaks (DSB). XR-1 was originally isolated by its hypersensitivity to killing with ionizing radiation, but we have also shown that it is sensitive to killing with bleomycin. In contrast, BL-10 was isolated by its extreme sensitivity to killing with bleomycin, and it is not cross-sensitive to other DNA breaking agents. A 1-h treatment of bleomycin induces a similar number of DNA double-strand breaks in XR-1, BL-10 and CHO cells. However, XR-1 is unable to repair bleomycin-induced DNA double-strand breaks, whereas BL-10 possesses the same kinetics of repair as parental CHO. These data lead us to conclude that at least two mechanisms of killing exist for bleomycin; one of them is DNA DSB-dependent, and the other seems to be DNA DSB-independent.
Giaccia
A J
AJ
Department of Radiation Oncology, Stanford University School of Medicine, CA 94305.
Shieh
J
J
Cholon
A
A
Brown
J M
JM
D000818:Animals; D001761:Bleomycin / Q000633:toxicity*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D004249:DNA Damage; D004260:DNA Repair; D004587:Electrophoresis, Agar Gel; D007700:Kinetics; D009154:Mutation / Q000187:drug effects
D001761:Bleomycin