ABSTRACT
A recently introduced disk for solid-phase extraction of pollutants from water (C18 Speedisk) has been tested for the analysis of polychlorinated dibenzo-p-dioxins (PCDD) and dibenzofurans (PCDF). The complete procedure of analysis has been validated with spiked deionized water. The accuracy, expressed as recovery for the sum of 2,3,7,8-substituted congeners. is 92% and the precision, expressed as the RSD of reproducibility, is 5.8%. The limit of detection (LOD), using 2 l of water, is 4.2 pg/l (0.6 pg ITEQ/l) for the sum of 2,3,7,8-substituted congeners. Actually, the C18 Speedisks have substituted the use of other C18 membrane disks in our laboratory because they allow the fast and efficient analysis of samples with high content of suspended material and reduce the time of elution of free-particulate samples. These disks have been successfully applied to the analysis of water from different sources and with very different physical and chemical characteristics: seawater, rain water, an industrial effluent, a landfill leachate and the inlet and chlorinated and non-chlorinated outlet water from a wastewater treatment plant.
Subject(s)
Benzofurans/analysis , Polychlorinated Dibenzodioxins/analysis , Soil Pollutants/analysis , Carbon/chemistry , Dibenzofurans, Polychlorinated , Environmental Monitoring/instrumentation , Environmental Monitoring/methods , Polychlorinated Dibenzodioxins/analogs & derivatives , Reproducibility of Results , Sensitivity and Specificity , Water Pollutants, Chemical/analysisABSTRACT
The genotoxic potency of certain classes of topoisomerase II poisons is correlated with their affinity to the topoisomerase protein rather than with the presence of 'classical' structural alerts for DNA reactivity: bacterial topoisomerase II poisons (specifically named gyrase inhibitors) are highly genotoxic in prokaryotic systems; mammalian topoisomerase II poisons are potent mutagens/clastogens in eukaryotic systems. Studies with bacterial, lower eukaryotic and mammalian genotoxicity tests were performed to draw structure-activity conclusions and address risk-benefit considerations for the class of quinolone gyrase inhibitors. All 17 gyrase inhibitors investigated in this study showed genotoxic activity in Salmonella typhimurium strain TA102 and the SOS test. The genotoxic and the toxic activities increased in a highly parallel fashion from the parent compounds, nalidixic acid and oxolinic acid, to the new generation fluoroquinolones. Generally, the most potent fluoroquinolones also show clear-cut positive effects in eukaryotic test systems, although at concentrations 100-1000-fold higher than those effective in bacteria and also 100-1000-fold higher than the minimal genotoxic concentrations of antitumour topoisomerase II inhibitors (ellipticine, teniposide, mAMSA) used as reference compounds. However, subtle structural modifications of the quinolones can strongly diminish the preferential genotoxicity in the prokaryotic test systems.
Subject(s)
Chromosome Aberrations , Enzyme Inhibitors/toxicity , Micronucleus Tests , Mutagenicity Tests , Mutagens/toxicity , Topoisomerase II Inhibitors , Animals , Biotransformation , CHO Cells , Cell Line , Cricetinae , Cricetulus , DNA Repair , Escherichia coli/drug effects , Escherichia coli/genetics , Eukaryotic Cells , Hypoxanthine Phosphoribosyltransferase/genetics , Lymphoma , Mice , Microsomes, Liver/metabolism , Molecular Structure , Mutagenesis , Prokaryotic Cells , Quinolones/toxicity , Rats , Saccharomyces cerevisiae/drug effects , Saccharomyces cerevisiae/growth & development , Salmonella typhimurium/drug effects , Structure-Activity Relationship , Tumor Cells, CulturedABSTRACT
Ro 5-4864 (4-chlorodiazepam), PK 11195 (1-(2-chlorophenyl)-1,3-dihydro-1-methyl-propyl)isoquinoline carboxamide) and diazepam inhibit, in a concentration-dependent way, the proliferation of V79 Chinese hamster lung cells (IC50 values were: 65.0 +/- 3.73 microM, 57.70 +/- 4.75 microM and 106.80 +/- 8.89 microM, respectively) without being cytotoxic. This antiproliferative effect is mediated by mitosis arrest in the G2 + M stage without affecting DNA synthesis and seems unrelated to a specific interaction of these drugs with the peripheral-type benzodiazepine receptor.
Subject(s)
Benzodiazepinones/pharmacology , Cell Division/drug effects , Diazepam/pharmacology , Isoquinolines/pharmacology , Animals , Calcium/metabolism , Cells, Cultured , Cricetinae , Cricetulus , DNA/analysis , Dose-Response Relationship, DrugABSTRACT
A rapid and simple procedure for the micronucleus test (MNT) in vitro using Chinese hamster ovary (CHO) cells was established in our laboratory. The assay is intended to quickly screen chromosomal aberrations in vitro within the framework of industrial genotoxicity studies. To test the sensitivity of the assay in the experiments described here, four substances, classified as noncarcinogens but reported as weak inducers of micronuclei (MN) in bone-marrow cells of mice, were evaluated in the MNT in vitro. Of the four compounds, ascorbic acid, phenol, and 2,6-diaminotoluene proved to be genotoxic in the MNT in vitro. Titanium dioxide, which could not be dissolved in the culture medium, did not induce MN. The MNT in vitro proved to be quick and relatively simple and to yield highly reproducible results when testing the four chemicals.
