Enhancement of an Mg(2+)-dependent nuclease activity in rat liver cells exposed to cisplatin.
An Mg(2+)-dependent deoxyribonuclease activity was highly purified from a 0.6 M NaCl extract of rat-liver nuclei. The template primer activity assay with a Klenow polymerase suggested that this nuclease plays a role in incision/excision of cisplatin-modified DNA strands to form single-strand gaps. In another experiment, rat-liver (Ac2F) cells were cultured in the presence of cisplatin. A 0.6 M NaCl extract was prepared from the cultured-cell nuclei and subjected to the activity blotting analysis [Seki et al. (1993) J. Chromatography 618, 147-166]. The nuclease activity of the extract was enhanced in response to cisplatin, but not in the presence of cycloheximide. These results imply that cisplatin-DNA lesions induce the Mg(2+)-dependent deoxyribonuclease activity in Ac2F cells to provide priming sites for the repair synthesis.
Hibino
Y
Y
Division of Cell Biology, Faculty of Pharmaceutical Sciences, Toyama Medical & Pharmaceutical University, Japan.
Kusashio
E
E
Terakawa
T
T
Sugano
N
N
D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000201:enzymology; D002945:Cisplatin / Q000494:pharmacology*; D003432:Cross-Linking Reagents; D003513:Cycloheximide / Q000494:pharmacology; D004247:DNA / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D004260:DNA Repair; D003851:Deoxyribonucleases / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000201:enzymology* / Q000648:ultrastructure; D008274:Magnesium / Q000494:pharmacology*; D010957:Plasmids; D051381:Rats; D014466:Ultraviolet Rays
D003432:Cross-Linking Reagents; D004247:DNA; D003513:Cycloheximide; D003851:Deoxyribonucleases; D008274:Magnesium; D002945:Cisplatin