Inactivation of O6-alkylguanine-DNA alkyltransferase in HeLa cells by cisplatin

Abstract

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.