title: Assessment of genotoxicity and acute toxic effect of the imatinib mesylate in plant bioassays.
abstract: Imatinib mesylate (IM) is at present one of the most widely used cytostatic drugs in developed countries but information on its ecotoxicological activities is scarce. This article describes the results of the first investigation in which genotoxic and acute toxic properties of the drug were studied in higher plants. IM was tested in two widely used plant bioassays namely in micronucleus (MN) assays with meiotic tetrad cells of Tradescantia (clone #4430) and in mitotic root tip cells of Allium cepa. Additionally, acute toxic effects (inhibition of cell division and growth of roots) were monitored in the onions. Furthermore, we studied the impact of the drug on the fertility of higher plants in pollen abortion experiments with three wildlife species (Chelidonium majus, Tradescantia palludosa and Arabidopsis thaliana). In MN assays with Tradesacantia a significant effect was seen with doses ⩾10μM; the Allium MN assay was even more sensitive (LOEL⩾1.0μM). A significant decrease of the mitotic indices was detected at levels ⩾10μM in the onions and reduction of root growth with ⩾100μM. In the pollen fertility assays clear effects were observed at doses ⩾147.3mgkg(-1). Data concerning the annual use of the drug in European countries (France, Germany, Slovenia) enable the calculation of the predicted environmental concentration (PEC) values which are in the range between 3.3 and 5.0ngL(-1). Although comparisons with the genotoxic potencies of other commonly used cytostatic drugs and with highly active heavy metal compounds show that IM is an extremely potent genotoxin in higher plants, it is evident that the environmental concentrations are ⩾5 orders of magnitude lower as the levels which are required to cause adverse effects.
authors.affiliation: Institute of Cancer Research, Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Borschkegasse 8a, A-1090 Vienna, Austria.
authors.forename: Clemens
authors.initials: C
authors.lastname: Pichler
authors.affiliation: National Institute of Biology, Večna pot 111, Ljubljana, Slovenia.
authors.forename: Metka
authors.initials: M
authors.lastname: Filipič
authors.affiliation: The Institute for Hygiene and Applied Immunology, Medical University of Vienna, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Kundi
authors.affiliation: Institute of Cancer Research, Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Borschkegasse 8a, A-1090 Vienna, Austria.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Rainer
authors.affiliation: Institute of Cancer Research, Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Borschkegasse 8a, A-1090 Vienna, Austria. Electronic address: siegfried.knasmueller@meduniwien.ac.at.
authors.forename: Siegfried
authors.initials: S
authors.lastname: Knasmueller
authors.affiliation: Institute of Cancer Research, Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Borschkegasse 8a, A-1090 Vienna, Austria.
authors.forename: Miroslav
authors.initials: M
authors.lastname: Mišík
mesh_terms: D000490:Allium / Q000187:drug effects / Q000502:physiology; D017360:Arabidopsis / Q000187:drug effects / Q000502:physiology; D001549:Benzamides / Q000633:toxicity*; D004249:DNA Damage / Q000187:drug effects; D004785:Environmental Pollutants / Q000633:toxicity*; D000068877:Imatinib Mesylate; D018519:Meristem / Q000187:drug effects / Q000502:physiology; D015162:Micronucleus Tests; D009153:Mutagens / Q000633:toxicity*; D019697:Onions / Q000187:drug effects / Q000502:physiology; D010879:Piperazines / Q000633:toxicity*; D018521:Plant Physiological Phenomena / Q000187:drug effects; D018517:Plant Roots / Q000187:drug effects / Q000502:physiology; D010944:Plants / Q000187:drug effects*; D011058:Pollen / Q000187:drug effects / Q000502:physiology; D011743:Pyrimidines / Q000633:toxicity*; D034823:Tradescantia / Q000187:drug effects / Q000502:physiology
chemical_list: D001549:Benzamides; D004785:Environmental Pollutants; D009153:Mutagens; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate
keywords: Allium; Imatinib; Micronucleus; Pollen abortion; Root growth; Tradescantia