Abstract:
:Topoisomerase II regulates DNA topology by generating transient double-stranded breaks. The anticancer drug etoposide targets topoisomerase II and is associated with the formation of secondary leukemias in patients. The quinone and catechol metabolites of etoposide may contribute to strand breaks that trigger leukemic translocations. To further analyze the characteristics of etoposide metabolites, we extend our previous analysis of etoposide quinone to the catechol. We demonstrate that the catechol is ∼2-3-fold more potent than etoposide and under oxidative reaction conditions induces high levels of double-stranded DNA cleavage. These results support a role for etoposide catechol in contributing to therapy-induced DNA damage.
journal_name
Chem Res Toxicoljournal_title
Chemical research in toxicologyauthors
Jacob DA,Gibson EG,Mercer SL,Deweese JEdoi
10.1021/tx400205nsubject
Has Abstractpub_date
2013-08-19 00:00:00pages
1156-8issue
8eissn
0893-228Xissn
1520-5010journal_volume
26pub_type
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