title: Analyses of combined effects of cytostatic drugs on micronucleus formation in the Tradescantia.
abstract: Recent experiments showed that 5-fluorouracil (5FU), cisplatin (CDDP), etoposide (ET), and imatinib mesylate (IM), which are currently among the most widely used anticancer drugs, cause damage of the genetic material in higher plants. The aim of the present study was to determine whether mixtures of these drugs cause synergistic or antagonistic effects which may have an impact on their environmental safety. Therefore, the effects of binary mixtures of these anticancer drugs on the induction of micronuclei (MN) which reflect structural and numerical chromosomal aberrations were assessed in Tradescantia tetrads. Synergistic/antagonistic effects were determined by comparison with single exposures that would be equally effective in a reference model of independent action. This comparison was performed at two distinct effect sizes. We found clear evidence for synergisms in combination experiments with IM and antagonism in a high-dose experiment with ET and 5FU. Our findings indicate that IM increases the genotoxic effects of other anticancer drugs. The maximal effects which we found were in the range between 19 and 38 % in the excess of effect sizes predicted under independent action. These effects may have an impact on the overall genotoxic activities of untreated hospital waste waters but not on the environment in general as the predicted environmental concentrations of the studied drugs are several orders of magnitude lower as the levels which are required to cause induction of MN in higher plants.
authors.affiliation: Institute for Cancer Research, Department of Internal Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Borschkegasse 8a, A-1090, Vienna, Austria.
authors.forename: Miroslav
authors.initials: M
authors.lastname: Mišík
authors.affiliation: Department for Genetic Toxicology and Cancer Biology, National Institute of Biology, Ljubljana, Slovenia.
authors.forename: Metka
authors.initials: M
authors.lastname: Filipic
authors.affiliation: Institute for Cancer Research, Department of Internal Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Borschkegasse 8a, A-1090, Vienna, Austria.
authors.forename: Armen
authors.initials: A
authors.lastname: Nersesyan
authors.affiliation: Department of Botany, Faculty of Natural Sciences, Comenius University, Bratislava, Slovakia.
authors.forename: Katarína
authors.initials: K
authors.lastname: Mišíková
authors.affiliation: Institute for Cancer Research, Department of Internal Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Borschkegasse 8a, A-1090, Vienna, Austria. siegfried.knasmueller@meduniwien.ac.at.
authors.forename: Siegfried
authors.initials: S
authors.lastname: Knasmueller
authors.affiliation: Medical University of Vienna, Institute of Environmental Health, Medical University of Vienna, Wien, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Kundi
mesh_terms: D054697:Cytostatic Agents / Q000633:toxicity*; D004249:DNA Damage; D004338:Drug Combinations; D015162:Micronucleus Tests; D034823:Tradescantia / Q000187:drug effects
chemical_list: D054697:Cytostatic Agents; D004338:Drug Combinations
keywords: Antagonism; Cytostatics; Micronuclei; Synergism; Tradescantia