Enhancement of bleomycin-induced DNA damage by exposing isolated DNA to high concentrations of the calcium antagonist verapamil.
The calcium antagonist verapamil was found to enhance synergistically the DNA (desoxyribonucleic acid) strand breakage activity of the radiomimetic antitumor agent bleomycin in vitro. The induction of single and double strand breaks in isolated DNA was investigated by agarose gel electrophoresis. Three types of DNA (two plasmids and one native eukaryotic DNA) were used as target molecules. The effect of verapamil was concentration dependent (concentration range tested: 0.75-3.0 mmol/l). However, at those low concentrations, as they were used in cytotoxicity assays and cytogenetic experiments, no potentiating effect of verapamil on bleomycin action could be observed. The significance of these findings is discussed with respect to various hypothesis concerning the potentiation of tumor drug efficiency by verapamil and other calcium antagonists.
Weber
J
J
Institut für Strahlenbiologie, Universität Münster, Fed. Rep. of Germany.
Scheid
W
W
Traut
H
H
D000818:Animals; D001761:Bleomycin / Q000494:pharmacology*; D004247:DNA / Q000187:drug effects*; D004249:DNA Damage; D004269:DNA, Bacterial / Q000187:drug effects; D004357:Drug Synergism; D004587:Electrophoresis, Agar Gel; D010957:Plasmids; D013768:Tetrahymena / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology*
D004269:DNA, Bacterial; D001761:Bleomycin; D004247:DNA; D014700:Verapamil