Inactivation of O6-alkylguanine-DNA alkyltransferase in HeLa cells by cisplatin.
Inactivation of O6-alkylguanine-DNA alkyltransferase (O6-AGT) in HeLa CCL2 cells by cisplatin was studied. HeLa CCL2 cells treated with cisplatin showed a dose-dependent decline in O6-AGT activity. After cisplatin was removed and replaced with fresh medium, the transferase level began to rise slowly. By 72 h slightly more than 80% of the activity was recovered. It seems that the activity of the alkyltransferase can be inactivated by platinated DNA adducts. The data suggest that the O6-platinum-guanine formation and the O6-alkyltransferase depletion are not responsible for cytotoxicity but may result in a base substitution mutation in mammalian cells.
Wang
L G
LG
Institute of Materia Medica, Chinese Academy of Medical Sciences, Beijing, China.
Setlow
R B
RB
D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D006367:HeLa Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D007700:Kinetics; D008780:Methyltransferases / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D019853:O(6)-Methylguanine-DNA Methyltransferase
D008780:Methyltransferases; D019853:O(6)-Methylguanine-DNA Methyltransferase; D002945:Cisplatin