Evidence of a reduced DNA topoisomerase II mRNA expression after ionizing radiation.
DNA topoisomerase II (top2) is a nuclear enzyme which resolves the topological constraints during DNA metabolism and is the target of some of the most active drugs used in cancer chemotherapy. Top2 is regulated both transcriptionally and post-transcriptionally and its expression is coupled to cell cycle position. To explore the regulation of top2 after DNA damage, we studied the behavior of cell lines of the National Cancer Institute Anticancer Drug Screen, previously characterized for p53 status, in response to ionizing radiation. The kinetics of top2 mRNA expression were measured using quantitative hybridization. A profound and transient decrease of top2 mRNA after irradiation was detected within four hours in 30% of the 25 cell lines tested. This transient top2 decrease in mRNA expression occurred independently of the p53 status of the cell lines and was not associated with increased apoptotic DNA fragmentation. This observation indicates that a transient decrease in top2 mRNA expression may occur after DNA damage and suggests the need for preferential schedule when planning the use of top2 inhibitors with ionizing radiation during combined radio-chemotherapy treatments.
Goldwasser
F
F
Division of Basic Sciences, National Cancer Institute, National Institute of Health, Bethesda, Maryland, USA. F. Goldwasser@wanadoo.fr
Bae
I
I
Pommier
Y
Y
Fornace
A J
AJ
D017209:Apoptosis; D004249:DNA Damage; D004250:DNA Topoisomerases, Type II / Q000235:genetics*; D015536:Down-Regulation; D015971:Gene Expression Regulation, Enzymologic / Q000528:radiation effects*; D006801:Humans; D012333:RNA, Messenger / Q000235:genetics*; D011839:Radiation, Ionizing; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D004250:DNA Topoisomerases, Type II