Abstract
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.
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