Predicting bioavailability of sediment-associated organic contaminants for Diporeia spp. and oligochaetes.

Biota-sediment accumulation factors (BSAF) were calculated for Diporeia spp. and oligochaete worms exposed to polychlorinated biphenyls (PCBs) and polycyclic aromatic hydrocarbons (PAHs) from field-collected sediment. These data were compared to the contaminant fraction extracted from sediment with Tenax resin using a 24 h extraction.

Kinetics of adsorption and desorption of some organochlorine compounds on black carbon in a sediment.

Rate constants for adsorption and desorption of four organochlorine compounds on black carbon in a sediment were determined from measurements of the rate of removal, by gas purge, of the organochlorine compounds as single solutes from a water-sediment mixture immediately after addition of the solute to the system. The rates of removal fitted to a kinetic scheme based on Langmuir adsorption onto two types of sites in black carbon. The first-order rate constants for desorption from these sites were comparable to those for slow and very slow desorption from sediment.

Influence of long contact times on sediment sorption kinetics of spiked chlorinated compounds.

The desorption kinetics of hexachlorobenzene (HCB) and 2,4,4'-trichlororbiphenyl (PCB 28) spiked to a field sediment were studied using a gas-purge technique. A contact time of up to 1,461 d was used to assess long-term changes in desorption kinetics. Purge-induced desorption experiments lasted from 300 to more than 4,000 h.

Temperature effects on very slow desorption of native chlorobenzenes from sediment to water.

The temperature dependence of the kinetics of very slow desorption of eight chlorobenzenes was studied in laboratory batch experiments on a field-contaminated sediment from Lake Ketelmeer, The Netherlands. The observed rate constants for very slow desorption averaged (1.5 +/- 0.

Tenax extraction mimics benthic and terrestrial bioavailability of organic compounds.

Biota to sediment accumulation factors (BSAFs) are widely used to describe the potential accumulation of organic contaminants in organisms. From field studies it is known that these BSAFs can vary dramatically between sediments of different origin, which is possibly explained by the variation in bioavailability of organic contaminants in sediments. In the present study it is shown that the variability in BSAF values for different sediment samples obtained at two Dutch freshwater sites could largely be explained by the variation in Tenax-extractable concentrations in these sediments.

Influence of desorption and contact time on sediment-water distribution of spiked polychlorinated biphenyls and polycyclic aromatic hydrocarbons: relation with in situ distribution.

The long-term sediment-water distribution of polychlorinated biphenyls (PCBs) and polycyclic aromatic hydrocarbons (PAHs), spiked to Lake Ketelmeer (The Netherlands) sediment, was studied using a gas-purge technique. Contact times varied from 2 to 1,461 d for the PCBs and from 5 to 100 d for the PAHs. Purge-induced desorption experiments lasted 300 to > 4,000 h.

Slow and very slow desorption of organic compounds from sediment: influence of sorbate planarity.

The kinetics of desorption of in situ chlorobenzenes, PAHs, and PCBs from four different sediments was studied employing Tenax beads as an infinite sink for sorbates. Rate constants for slow desorption were 2.9+/-0.

Resistant sorption of in situ chlorobenzenes and a polychlorinated biphenyl in river Rhine suspended matter.

The desorption kinetics of in situ chlorobenzenes (dichlorobenzenes, pentachlorobenzene and hexachlorobenzene) and 2,4,4'-trichlorobiphenyl (PCB-28) were measured with a gas-purge technique for river Rhine suspended matter sampled in Lobith, The Netherlands. This suspended matter is the main source of sediment accumulation in lake Ketelmeer. In lake Ketelmeer sediment earlier observations showed that slow and very slow fractions dominate the desorption profile.

BNP7787, a novel protector against platinum-related toxicities, does not affect the efficacy of cisplatin or carboplatin in human tumour xenografts.

BNP7787 (2',2'-dithio-bis-ethane sulphonate sodium), a water-soluble disulphide, is chemically and mechanistically different from other sulphur-containing chemoprotective agents. Presently, BNP7787 is under investigation for its protective properties with regard to the side-effects of platinum compounds. In this study, we evaluated BNP7787, mesna and amifostine for their effects on the antitumour activity of platinum compounds.

Variation in the kinetics of caspase-3 activation, Bcl-2 phosphorylation and apoptotic morphology in unselected human ovarian cancer cell lines as a response to docetaxel.

Paclitaxel is able to cause cell death through the induction of apoptosis. Cell death characteristics for docetaxel have not yet been described in detail. We investigated four unselected human ovarian cancer cell lines for the sensitivity to a 1hr exposure to docetaxel and calculated the concentrations inhibiting 50% (IC(50)) and 90% (IC(90)) of cell growth.

Time-dependent changes in factors involved in the apoptotic process in human ovarian cancer cells as a response to cisplatin.

Objectives: Apoptosis is believed to be a major mechanism of cisplatin-induced cell death. We investigated the kinetics of apoptosis in four human ovarian cancer cell lines treated with cisplatin to obtain insight into the role and the behavior of a variety of factors involved in this process.

Methods: The cell lines A2780, H134, and IGROV-1 (all wild-type p53) and OVCAR-3 (mutant p53) were exposed to cisplatin for 1 h and the antiproliferative effects were measured after 96 h.

Induction of vascular endothelial growth factor expression and hypoxia-inducible factor 1alpha protein by the oxidative stressor arsenite.

Recent evidence suggests that vascular endothelial growth factor (VEGF) expression is up-regulated by oxidative stressors through activation of hypoxia-inducible Factor 1 (HIF-1). To investigate whether this is a general phenomenon, we studied the effects of the sulfhydryl reagent arsenite on VEGF expression in human ovarian cancer cells. Arsenite potently induces the production of reactive oxygen species (ROS) in several cell systems and directly interacts with sulfhydryl groups of cellular thiols.

Drug resistance features and S-phase fraction as possible determinants for drug response in a panel of human ovarian cancer xenografts.

Multidrug resistance (MDR) and more specifically the expression of P-glycoprotein (Pgp) have been studied extensively in vitro. Unfortunately, it appears that the predictive value of MDR recognized in vitro is mostly an incorrect measure to determine the responsiveness of a particular tumour in the clinic. This misunderstood or overvalued role of MDR might explain the failure of strategies to reverse Pgp function by the use of modulators in solid tumours.

The influence of P170-glycoprotein modulators on the efficacy and the distribution of vincristine as well as on MDR1 expression in BRO/mdr1.1 human melanoma xenografts.

Multidrug resistance modulators may increase the antitumour efficacy of drugs affected by P170-glycoprotein (Pgp) in Pgp-positive tumours in vivo. Inhibition of Pgp function in normal tissues, however, may enhance side-effects. Dexniguldipine-HCl, its analogues B9203-009 and B9303-036, and the dipyridamole derivative BIBW22BS could reverse vincristine (VCR) resistance in BRO/mdr1.

CPT-11 sensitivity in relation to the expression of P170-glycoprotein and multidrug resistance-associated protein.

The relevance of P170-glycoprotein (P-gp) and multidrug resistance-associated protein (MRP) for the sensitivity to CPT-11 was investigated in human malignant cell lines as well as in human tumour xenografts. In vitro, the P-gp-positive sublines BRO/mdr1.1 (transfected with MDR1) and 2780AD were slightly cross-resistant against carboxylesterase-activated CPT-11.

6-Mercaptopurine: cytotoxicity and biochemical pharmacology in human malignant T-lymphoblasts.

The effects of prolonged exposure to 2 and 10 microM 6-mercaptopurine (6MP) in the human lymphoblastic T-cell line MOLT-4 were studied with respect to cell-kinetic parameters, phosphoribosyl pyrophosphate (PRPP) and purine ribonucleotide levels, formation of 6MP-nucleotides, especially methyl-thio-IMP (Me-tIMP), DNA and RNA synthesis ([32P] incorporation), and [8-14C]6MP incorporation into newly synthesized DNA and RNA. The results provided new insights into the complex mechanism of action of 6MP in human malignant lymphoblasts. Exposure to 2 microM 6MP resulted in a rapid inhibition of purine de novo synthesis (PDNS) by increased levels of Me-tIMP, resulting in increased PRPP levels and decreased purine ribonucleotides, affecting cell growth and clonal growth, and less cell death.

Effects of methotrexate on purine and pyrimidine metabolism and cell-kinetic parameters in human malignant lymphoblasts of different lineages.

MOLT-4 (T-), RAJI (B-), and KM-3 (non-B-non-T-, common ALL) malignant lymphoblasts demonstrated significant differences in their activities of purine de novo synthesis (PDNS) and purine salvage pathway and in their cell-kinetic parameters. Incubations with concentrations of methotrexate (0.02 and 0.

Purine de novo synthesis as the basis of synergism of methotrexate and 6-mercaptopurine in human malignant lymphoblasts of different lineages.

Methotrexate (MTX) causes an inhibition of purine de novo synthesis (PDNS), resulting in increased intracellular availability of 5-phosphoribosyl-1-pyrophosphate (PRPP) in human malignant lymphoblasts with an active PDNS. Normal bone marrow cells and peripheral blood lymphocytes lack this capacity. The increased levels of PRPP can be used for enhanced incorporation of 6-mercaptopurine (6MP), indicating a potential time-, sequence- and dose-dependent synergism of both drugs.

Dose-related effects of methotrexate on purine and pyrimidine nucleotides and on cell-kinetic parameters in MOLT-4 malignant human T-lymphoblasts.

The effects of methotrexate (MTX) on cytotoxicity (trypan blue exclusion and soft agar clonal growth), cell cycle perturbation, and purine and pyrimidine ribonucleotide and deoxyribonucleotide pools have been studied in MOLT-4 malignant T-lymphoblasts. Two concentrations of MTX, 0.02 microM and 0.

Sequence-, time- and dose-dependent synergism of methotrexate and 6-mercaptopurine in malignant human T-lymphoblasts.

Methotrexate (MTX) and 6-mercaptopurine (6MP) are common drugs in the oral maintenance therapy of acute lymphoblastic leukemia (ALL). On the basis of their biochemical effects on cell metabolism, a sequence-dependent synergism might be anticipated. In order to investigate this hypothesis, MOLT-4 human malignant T-lymphoblasts were incubated with various concentrations of MTX.

A differential DNA-repair test using mixtures of E. coli K12 strains in liquid suspension and animal-mediated assays.

The feasibility of performing tests for repairable DNA damage in animal assay procedures was investigated by using repair-proficient and repair-deficient derivatives of E. coli K12 strain 343/113, including mutations in the uvrB, recA, polA and dam genes. To avoid variations in the relative recovery of viable cells from different samples, the strains were further marked with auxotrophic growth requirements, so that mixtures could be treated and the survival of each strain determined individually on media containing the corresponding growth factors.