Changes in deoxyribonucleic acid linking number due to treatment of mammalian cells with the intercalating agent 4'-(9-acridinylamino)methanesulfon-m-anisidide.
Treatment of mammalian cells with DNA intercalating agents produces protein-associated DNA strand breaks. These breaks have been proposed to represent the action of a topoisomerase, which would alter the DNA linking number. Changes in DNA linking number in cells treated with the intercalating agent 4'-(9-acridinylamino)methanesulfon-m-anisidide (m-AMSA) were studied by ethidium titration of nucleoid sedimentation. m-AMSA treatment was found to produce an increase in DNA linking number. Previously, we had proposed that intercalator-induced protein-associated DNA breaks act to reduce DNA torsional strain that results from the intercalator-induced decrease in DNA twist. In such a model, linking number would be expected to decrease. The finding that the DNA linking number increased following m-AMSA treatment suggests that intercalators may block enzymes that normally decrease linking number. Such enzymes would have DNA gyrase like properties. Consistent with this possibility, a DNA gyrase inhibitor, novobiocin, inhibited the restoration of normal linking number and, to a lesser degree, the reversal of protein-associated strand breaks after removal of intercalator.
D000609:Aminoacridines / Q000494:pharmacology*; D000677:Amsacrine; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism*; D004273:DNA, Neoplasm / Q000378:metabolism*; D003852:Deoxyribonucleoproteins / Q000378:metabolism*; D004996:Ethidium / Q000494:pharmacology; D007364:Intercalating Agents / Q000494:pharmacology*; D007700:Kinetics; D007939:Leukemia L1210 / Q000378:metabolism*; D051379:Mice; D009675:Novobiocin / Q000494:pharmacology
D000609:Aminoacridines; D001549:Benzamides; D004273:DNA, Neoplasm; D003852:Deoxyribonucleoproteins; D007364:Intercalating Agents; D000677:Amsacrine; D009675:Novobiocin; C025160:3-aminobenzamide; D004996:Ethidium