Evidence of a reduced DNA topoisomerase II mRNA expression after ionizing radiation

DNA topoisomerase II (top2) is a nuclear enzyme which resolves the topologi cal constraints during DNA metabolism and is the target of some of the most active drugs used in cancer chemotherapy. Top2 is regulated both transcrip tionally and post- transcriptionally and its expression is coupled to cell cycle position. To explore the regulation of top2 after DNA damage, we stud ied the behavior of cell lines of the National Cancel Institute Anticancer Drug Screen, previously characterized for p53 status, in response to ionizi ng radiation. The kinetics of top2 mRNA expression were measured using quan titative hybridization. A profound and transient decrease of top2 mRNA afte r irradiation was detected within four hours in 30 % of the 25 cell lines t ested This transient top2 decrease in mRNA expression occured independently of the p53 status of the cell lines and was not associated with increased apoptotic DNA fragmentation. This observation indicates that a transient de crease in top2 mRNA expression may occur after DNA damage and suggests the need for preferential schedule when planning the use of top2 inhibitors wit h ionizing radiation during combined radio-chemotherapy treatments.