[Calcium antagonists as amplifiers of the mutagenicity of cytostatic drugs].
Some calcium antagonists enhance synergistically the mutagenic efficiency of cytostatics. The results so far obtained concerning this phenomenon are described and discussed: (1) chromosome aberrations induced (in vitro) in human lymphocytes (cytostatics; bleomycin and peplomycin; calcium antagonists: verapamil and fendiline), (2) chromosome and chromatid aberrations induced (in vitro) in Chinese hamster ovary (CHO) cells (cytostatic: mitomycin C; calcium antagonist: verapamil), (3) gene mutations induced in the bacterium Salmonella typhimurium (cytostatics: mainly various anilinoacridine drugs; calcium antagonist: verapamil). In all 3 studies neither verapamil nor fendiline proved to be mutagenic when applied alone. The "comutagenicity" of calcium antagonists is compared with the enhancement of the cytotoxic (cell killing) efficiency of cytostatics by calcium antagonists. Both phenomena--potentiation of mutagenicity and of cytotoxicity--are interpreted on the basis of the "accumulation hypothesis". According to this hypothesis those calcium antagonists would enhance the mutagenic and cytotoxic efficiency of the cytostatics by inhibiting their extrusion from the cell. Consequently, the cytostatics would be accumulated in the cell and this would increase their mutagenic and cytotoxic efficiency. Since not all calcium antagonists investigated so far enhance the mutagenicity and cytotoxicity of cytostatics, this potentiation seems not to be caused by their calcium antagonistic action per se. Molecular, evolutionary, and medical aspects of the "accumulation hypothesis" are shortly discussed.
Scheid
W
W
Institut für Strahlenbiologie, Universität Münster, Deutschland.
Traut
H
H
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002869:Chromosome Aberrations; D004357:Drug Synergism; D006801:Humans; D009152:Mutagenicity Tests
D000970:Antineoplastic Agents; D002121:Calcium Channel Blockers
Kalziumantagonisten als Wirkverstärker der Mutagenität von Zytostatika.