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  • Title: Inactivation of O6-alkylguanine-DNA alkyltransferase in HeLa cells by cisplatin.
    Author: Wang LG, Setlow RB.
    Journal: Carcinogenesis; 1989 Sep; 10(9):1681-4. PubMed ID: 2766459.
    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.
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