Nonproductive Rearrangement of DNA Topoisomerase I and II Genes: Correlation With Resistance to Topoisomerase Inhibitors
- 15 November 1989
- journal article
- research article
- Published by Oxford University Press (OUP) in JNCI Journal of the National Cancer Institute
- Vol. 81 (22) , 1732-1735
- https://doi.org/10.1093/jnci/81.22.1732
Abstract
Topoisomerase inhibitors comprise an important group of agents that is used in cancer treatment. Because the development of resistance to cancer chemotherapeutic agents represents a major limitation of cancer chemotherapy, we investigated the mechanism of resistance by murine P388 leukemia to camptothecin (topoisomerase I inhibitor) or amsacrine (topoisomerase II inhibitor). The resistant cells contained reduced levels of topoisomerase activity and messenger RNA. The topoisomerase gene of these cells was rearranged (only in one allele) and hypermethylated. These topoisomerase gene alterations probably resulted in reduced transcription and, thus, enzyme production, which was correlated with resistance to the topoisomerase inhibitor. [J Natl Cancer Inst 81:1732–1735, 1989]This publication has 1 reference indexed in Scilit:
- Elevated DNA topoisomerase II activity in nitrogen mustard-resistant human cells.Proceedings of the National Academy of Sciences, 1987