Enhanced sensitivity to topoisomerase inhibitors in synchronous CHO cells pre-treated with 5-azacytidine.
Multidrug combination has been shown to be very useful to improve antitumor activity as well as to reduce the toxicity of different anti-cancer drugs. We have evaluated the interaction between the hypomethylating agent 5-azacytidine and the topoisomerase I and topoisomerase II inhibitors Camptothecin (CPT) and 4'-(9-acridinylamino) methanesulfon-m-anisidide (m-AMSA) respectively, based on the hypothesis that through the alteration of chromosome replication timing following DNA hypomethylation, the number of replication forks in early S phase might increase, so enhancing the probability of a collision between a blocked cleavable complex (DNA-topo I-CPT or DNA-topo II-m-AMSA) and a replication fork. We have tested the capacity of CPT and m-AMSA to induce chromosomal aberrations as well as reproductive cell death in synchronous cultured Chinese hamster ovary cells after a pretreatment with 5-azacytidine with positive results.
López-Baena
M
M
Department of Cell Biology, Faculty of Biology, University of Seville, Seville, Spain.
Mateos
S
S
Piñero
J
J
Trinidad Ortiz
Cortés
F
F
D000677:Amsacrine / Q000494:pharmacology; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D001374:Azacitidine / Q000494:pharmacology*; D016466:CHO Cells; D002166:Camptothecin / Q000494:pharmacology; D002869:Chromosome Aberrations; D006224:Cricetinae; D019175:DNA Methylation; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016196:S Phase; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors
D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D004791:Enzyme Inhibitors; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D000677:Amsacrine; D001374:Azacitidine; D002166:Camptothecin