Induction of DNA double-strand breaks in Chinese hamster V79 cells by 2-chlorodeoxyadenosine.
2-Chlorodeoxyadenosine was found to induce DNA double-strand breaks as well as cell death in log-phase Chinese hamster V79 cells. The induction of DNA double-strand breaks, measured by a neutral elution technique, was observed after a 2-h incubation of the cells in the presence of 5 microM of 2-chlorodeoxyadenosine, but these breaks were almost rejoined by a subsequent 1-h incubation, even though this drug was present in the medium during incubation. This repair was prevented by the addition of nicotinamide, which is known to inhibit poly(ADP-ribose) synthesis that is strongly associated with the DNA ligation, but not prevented by the addition of 9-beta-D-arabinofuranosyladenine (araA), which is known to inhibit DNA polymerization. These results suggest that the repair of CdA-induced double-strand breaks is achieved by ligation alone without DNA polymerization. When 35 microM of cycloheximide and 1.3 mM of dibutyryl cAMP were added to the medium, it was found that the induction of double-strand breaks by 2-chlorodeoxyadenosine was suppressed, while the cytotoxicity of 2-chlorodeoxyadenosine measured by colony-forming ability was not interfered with. These results suggest that the induction of DNA double-strand breaks is not associated with the cytotoxicity of this drug.
Tanabe
K
K
Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
Hiraoka
W
W
Kuwabara
M
M
Sato
F
F
Matsuda
A
A
Ueda
T
T
D015762:2-Chloroadenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002460:Cell Line; D017338:Cladribine; D006224:Cricetinae; D003412:Cricetulus; D003513:Cycloheximide / Q000494:pharmacology; D004247:DNA / Q000187:drug effects / Q000302:isolation & purification; D004249:DNA Damage; D003839:Deoxyadenosines / Q000494:pharmacology*; D007700:Kinetics; D008168:Lung; D011865:Radioisotope Dilution Technique; D013936:Thymidine / Q000378:metabolism; D014316:Tritium
D003839:Deoxyadenosines; D014316:Tritium; D015762:2-Chloroadenosine; D017338:Cladribine; D003994:Bucladesine; D004247:DNA; D003513:Cycloheximide; D013936:Thymidine