Enhancement of cytogenetic and cytotoxic effects on multidrug-resistant (MDR) cells by a calcium antagonist (verapamil).
The cytogenetic effects of a calcium antagonist, verapamil, on anticancer antibiotic-induced chromosomal damage and cytotoxicity were studied in multidrug-resistant (MDR) Chinese hamster ovary (CHO) cells in vitro. Nine colchicine-resistant (CHr) sublines were obtained by stepwise culturing with increasing concentrations of colchicine. Compared with the parent CHO cells, CHr sublines exhibited an approximately 2.6- to 120-fold higher resistance to colchicine. CHr sublines were cross-resistant to mitomycin C (MMC), actinomycin D (ACD), daunomycin (DM), bleomycin (BLM) and adriamycin (ADM). These anticancer antibiotics are known to induce chromosomal aberrations in various cell types. However, one MDR subline, CHr-500, showed resistance to induction of chromosomal aberrations by MMC. In CHr-500 cells, verapamil at a non-toxic concentration of 10 micrograms/ml enhanced the MMC-induced chromosomal damage and cytotoxicity to the levels seen in the sensitive parent cells. The increase in chromosomal damage in the presence of verapamil was correlated with the increase in cytotoxicity.
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Toxicology Department, Tanabe Seiyaku Co. Ltd., Osaka, Japan.
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D002478:Cells, Cultured; D002875:Chromosomes / Q000187:drug effects*; D003078:Colchicine / Q000494:pharmacology; D004351:Drug Resistance; D004357:Drug Synergism; D014700:Verapamil / Q000494:pharmacology*
D000903:Antibiotics, Antineoplastic; D014700:Verapamil; D003078:Colchicine