title: Acute toxic and genotoxic activities of widely used cytostatic drugs in higher plants: Possible impact on the environment.
abstract: Cytostatic drugs are highly toxic pharmaceuticals and it was repeatedly postulated that they may cause adverse effects in ecosystems. The acute toxic and genotoxic properties of these drugs have not been adequately investigated in higher plants so far; therefore, we studied the most widely used drugs (5-flurouracil, 5FU; etoposide, Et; cisplatin, CisPt; carboplatin, CaPt; vincristine sulfate, VinS and cyclophosphamide monohydrate, CP) in micronucleus (MN) assays with meiotic pollen tetrad cells of Tradescantia and with root cells from Allium cepa. MNi are formed as a consequence of chromosome breaks and aneuploidy. We monitored also the acute toxic properties of the drugs, i.e. inhibition of cell division (mitotic indices and retardation of root growth) in the latter species. All compounds caused in both indicator plants genotoxic effects. The order of genotoxic potencies expressed as NOELs in µM was CisPt (0.1)≥ Et (0.5)>CP (1.0)>CaPt (10)>5FU (30)>VinS (100) in Tradescantia. A similar order was seen in Allium MN but Et was less active (5.0µM). Four compounds caused alterations of the mitotic indices under the present conditions namely CisPt (0.5), Et (10.0), 5FU (10.0) and VinS (100). Inhibition of root growth decreased in the order CisPt (0.5)>Et (1.0)≥VinS (1.0)>5FU (5.0)>CaPt (33.0)>CP (>1000). Comparisons of the NOELs with the predicted environmental concentrations (PEC) show that the latter values are at least 5 orders of magnitude lower and indicate that it is unlikely that their release in the environment may cause adverse effects in higher plants. However, it is notable that the levels of both platinum compounds and of 5FU in hospital effluents may reach levels which may induce damage of the genetic material.
authors.affiliation: Institute for Cancer Research, Department of Internal Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
authors.forename: Miroslav
authors.initials: M
authors.lastname: Mišík
authors.affiliation: Institute for Cancer Research, Department of Internal Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
authors.forename: Clemens
authors.initials: C
authors.lastname: Pichler
authors.affiliation: Institute for Cancer Research, Department of Internal Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Rainer
authors.affiliation: 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, Vienna, Austria.
authors.forename: Armen
authors.initials: A
authors.lastname: Nersesyan
authors.affiliation: Institute for Cancer Research, Department of Internal Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria. Electronic address: siegfried.knasmueller@meduniwien.ac.at.
authors.forename: Siegfried
authors.initials: S
authors.lastname: Knasmueller
mesh_terms: D000490:Allium / Q000187:drug effects*; D000782:Aneuploidy; D019457:Chromosome Breakage / Q000187:drug effects*; D003520:Cyclophosphamide / Q000633:toxicity; D054697:Cytostatic Agents / Q000633:toxicity*; D005047:Etoposide / Q000633:toxicity; D005472:Fluorouracil / Q000633:toxicity; D015162:Micronucleus Tests; D019055:No-Observed-Adverse-Effect Level; D009944:Organoplatinum Compounds / Q000633:toxicity; D018517:Plant Roots / Q000166:cytology / Q000187:drug effects; D011058:Pollen / Q000187:drug effects; D018675:Toxicity Tests / Q000379:methods*; D034823:Tradescantia / Q000187:drug effects*; D014750:Vincristine / Q000633:toxicity
chemical_list: D054697:Cytostatic Agents; D009944:Organoplatinum Compounds; D014750:Vincristine; D005047:Etoposide; D003520:Cyclophosphamide; D005472:Fluorouracil
keywords: Allium; Cytostatics; EC(50); Micronuclei; Tradescantia