Inhibition of DNA synthesis and cytotoxic effects of some DNA topoisomerase II and gyrase inhibitors in Chinese hamster V79 cells.
In this study, some DNA topoisomerase II and gyrase inhibitors have been identified as inhibitors of polymerization of deoxyribonucleotides [novobiocin (NVB), nalidixic acid (NDA), oxolinic acid (OXA)], or inhibitors of replicon initiation and DNA-chain elongation [etoposide (VP-16), teniposide (VM-26), 4'-(9-acridinylamino)methansulfon-m-anisidine (m-AMSA), ellipticine (ELT)]. The inhibitors of deoxyribonucleotide polymerization produced a significant (greater than 85%) suppression of [3H]thymidine incorporation into V79 cells within 20 min of treatment, followed by a rapid recovery of DNA synthesis, and reduced cell killing. In contrast, the inhibitors of replicon initiation and DNA-chain elongation needed about 60 min to induce a partial, but irreversible inhibition of DNA replication, associated with extensive cell killing.
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Department of Radiology and Radiation Biology, Colorado State University, Fort Collins 80523.
D000818:Animals; D002458:Cell Fractionation; D002467:Cell Nucleus; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004261:DNA Replication / Q000187:drug effects* / Q000528:radiation effects; D003854:Deoxyribonucleotides / Q000378:metabolism; D012093:Replicon / Q000187:drug effects; D059005:Topoisomerase II Inhibitors
D003854:Deoxyribonucleotides; D059005:Topoisomerase II Inhibitors