title: A novel use for the comet assay: detection of topoisomerase II inhibitors.
abstract: BACKGROUND
  The simple and quick comet assay can quantitatively detect DNA cleavage in cells. This study aimed to determine whether the comet assay could be used to detect topoisomerase (topo) II inhibitors.
  
  
  METHODS
  HT-29 colon cancer cells were pre-incubated with aclarubicin, a topo II antagonist, then treated with topo II poisons: etoposide (VP-16), teniposide (VM-26), 4'-(acridinylamino) methansulfon-m-anisidide (m-AMSA) and adriamycin (doxorubicin). We also tested a topo I poison (camptothecin) and a microtubule depolymerization inhibitor (taxol).
  
  
  RESULTS
  Aclarubicin significantly reduced DNA cleavage induced by topo II poisons, but not that induced by camptothecin. In HL-60/MX2 cells (containing no topo II beta and reduced topo II alpha), DNA breakage induced by topo II poisons was lower. Also, aclarubicin antagonized topo I-mediated camptothecin-induced DNA cleavage in these resistant cells.
  
  
  CONCLUSIONS
  The comet assay can be used to detect topo II poisons in cultured cells. Also, aclarubicin has a dual topo I and topo II antagonism, with "preferential antagonism" of topo II when topo II beta catalytic activity is normally expressed.
authors.affiliation: University of Illinois at Chicago, College of Medicine, Department of Surgical Oncology (M/C 820) 60612, USA.
authors.forename: G I
authors.initials: GI
authors.lastname: Salti
authors.forename: T K
authors.initials: TK
authors.lastname: Das Gupta
authors.forename: A I
authors.initials: AI
authors.lastname: Constantinou
mesh_terms: D015250:Aclarubicin / Q000494:pharmacology; D000677:Amsacrine / Q000494:pharmacology; D002166:Camptothecin / Q000494:pharmacology; D020552:Comet Assay; D004247:DNA / Q000187:drug effects; D004249:DNA Damage; D004317:Doxorubicin / Q000494:pharmacology; D005047:Etoposide / Q000494:pharmacology; D018922:HL-60 Cells; D019073:HT29 Cells; D006801:Humans; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology*; D017239:Paclitaxel / Q000494:pharmacology; D013713:Teniposide / Q000494:pharmacology; D059005:Topoisomerase II Inhibitors
chemical_list: D019384:Nucleic Acid Synthesis Inhibitors; D059005:Topoisomerase II Inhibitors; D000677:Amsacrine; D005047:Etoposide; D015250:Aclarubicin; D004317:Doxorubicin; D004247:DNA; D013713:Teniposide; D017239:Paclitaxel; D002166:Camptothecin