Mutagenicity of some topoisomerase II-interactive agents

ABSTRACT

Among the anticancer drugs currently used in the treatment of human malignancies, as well as several new series of drugs under development, are targeted at topoisomerase II enzymes. Besides of inducing cell death due to both 'mitotic catastrophe' and the induction of apoptosis, topoisomerase-II-targeted drugs can increase the frequency of cells bearing mutations. These cells can develop resistance to the therapeutic agents or may lead to the development of secondary tumours and abnormal reproductive outcomes. This review focuses on the mutagenic properties of the topoisomerase II poisons etoposide, doxorubicin and amsacrine, which are front-line therapies for a variety of malignancies, and genistein, which is prominent in soybean foods and is believed to be a chemopreventative agent that contributes to the low incidence of specific cancers among Asian populations. In addition, the topoisomerase II catalytic inhibitor merbarone that is in clinical trials as an anticancer agent will be discussed. It clear from the present review that, the topoisomerase II-interactive anticancer agents appear to be mutagenic. Therefore, the clinical use of these mutagenic drugs must be weighed against the risks of secondary malignancies in cured patients and persistent genetic damage of their potential offspring