We have isolated, following one-step mutagenesis, a Chinese hamster ovary cell mutant hypersensitive to the intercalating agent, adriamycin (4-fold compared to parental CHO-K1 cells). This agent exerts at least part of its cytotoxic action via inhibition of the nuclear enzyme, topoisomerase II. The mutant, designated ADR-3, showed hypersensitivity to all classes of topoisomerase II inhibitors, ...

Acute myeloid leukaemia (AML) is characterized by a block in differentiation and an unregulated proliferation of myeloid progenitor cells. While the cause of AML in children is unknown, risk factors that have been identified include exposure to toxins such as ethanol, pesticides and dietary topoisomerase II inhibitors, prior chemotherapy with alkylating agents or topoisomerase II inhibitors, co...

Gametocytocidal activities of pyronaridine and DNA topoisomerase II inhibitors against two isolates of multidrug-resistant Plasmodium falciparum, KT1 and KT3 were determined. After sorbitol treatment, pure gametocyte cultures of Plasmodium falciparum containing mostly young gametocytes (stage II and III) obtained on day 11 were exposed to the drugs for 48 h. The effect of the drugs on gametocyt...

DNA topoisomerases are ubiquitous enzymes that alter the configuration or topology of DNA. These enzymes play an important role in replicational, recombinational, and transcriptional events and are a key to cell growth processes. A number of therapeutically useful drugs apparently exert their effects by interfering with DNA topoisomerization reactions. Several inhibitors of bacterial DNA topois...

The antitrypanosomal and antifiliarial drug suramin is currently under investigation for treatment of advanced malignancies including prostatic cancer, adrenocortical cancer, and some lymphomas and sarcomas. Here we show that suramin is a potent inhibitor of the nuclear enzyme DNA topoisomerase II. Suramin inhibited purified yeast topoisomerase II with an IC50 of about 5 microM, as measured by ...

In this study the effect of eight DNA topoisomerase inhibitors on the growth Trypanosoma rangeli epimastigotes in cell culture was investigated. Among the eight compounds tested, idarubicin was the only compound that displayed promising trypanocidal activity with a half-maximal growth inhibition (GI(50)) value in the sub-micromolar range. Fluorescence-activated cell sorting analysis showed a re...