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At least 91 records · Page 5Linked to original sources
PubMed1992

Mechanism of cadmium-decreased glucuronidation in the rat.

In isolated rat hepatocytes, cadmium (0-200 microM) decreased the overall glucuronidation of both isopropyl N-(3-chloro-4 hydroxyphenyl)carbamate (4-hydroxychlorpropham, 4-OHCIPC) and 4-nitrophenol in a concentration-dependent manner. In contrast, in native rat liver microsomes, glucuronidation of 4-OHCIPC was increased by cadmium through activation of microsomal 4-OHCIPC glucuronosyl transferase. In addition, in rat microsome incubations, the net amount of 4-OHCIPC glucuronide was also indirectly increased by cadmium through a reduction in the activity of beta-glucuronidase. As the effect of cadmium on the activity of 4-OHCIPC glucuronosyl transferase could not account for the decrease in glucuronide formation in intact hepatocytes, the influence of cadmium on the availability of UDP-glucuronic acid (UDPGA) was investigated further. In isolated rat hepatocytes, cadmium depleted the UDPGA content in a dose-dependent manner without a change in the UDP glucose (UDPG) content. Cadmium did not increase the breakdown of UDPGA by microsomal UDPGA pyrophosphatase but strongly decreased (30-66%) the synthesis of the cofactor in the cytosol by inhibiting UDP-glucose dehydrogenase (UDPGDH). Cadmium (10-50 microM) was found to inhibit the purified enzyme from bovine liver (EC 1.1.1.22) non-competitively. In vivo in the absence of a substrate undergoing glucuronidation, cadmium administration, 1.5 and 2.5 mg Cd/kg i.v., to normally fed rats resulted in a 15 and 30% decrease of hepatic UDPGA, respectively. However, in the liver, neither the NAD+/NADH ratio nor the UDPG content was significantly changed following cadmium treatment. Both in vitro and in vivo results support the conclusion that in intact cells the reduction in overall 4-OHCIPC glucuronidation caused by cadmium was due to a decrease in UDPGA availability which results from the inhibiting effect of cadmium on UDPGDH.

Animals↗
PubMed1986

Na+-coupled D-glucose uptake and membrane order of enterocyte brush border membrane vesicles, under the effect of a series of N-phenylcarbamates.

The importance of the hydrophobic effect of exogenous substances and of modifications of membrane order on D-glucose uptake are still poorly defined. Our results show that the concentrative Na+ -coupled D-glucose uptake of rat enterocyte brush border membrane vesicles is inhibited by N-phenylcarbamates increase the membrane order. However, since the concentrations required for membrane order increase are much greater than those active on D-glucose uptake, the effects on lipid order cannot be responsible for the inhibition of D-glucose uptake. Measurements of D-glucose uptake under conditions of Na+ equilibrium show that these carbamates do not act directly on the carrier but indirectly by favouring the dissipation of the Na+ gradient.

Animals↗
PubMed2006

Assessment of uncertainty in a probabilistic model of consumer exposure to pesticide residues in food.

The assessment of consumer exposure to pesticides is an important part of pesticide regulation. Probabilistic modelling allows analysis of uncertainty and variability in risk assessments. The output of any assessment will be influenced by the characteristics and uncertainty of the inputs, model structure and assumptions. While the use of probabilistic models is well established in the United States, in Europe problems of low acceptance, sparse data and lack of guidelines are slowing the development. The analyses in the current paper focused on the dietary pathway and the exposure of UK toddlers. Three single food, single pesticide case studies were used to parameterize a simple probabilistic model built in Crystal Ball. Data on dietary consumption patterns were extracted from National Diet and Nutrition Surveys, and levels of pesticide active ingredients in foods were collected from Pesticide Residues Committee monitoring. The effect of uncertainty on the exposure estimate was analysed using scenarios, reflecting different assumptions related to sources of uncertainty. The most influential uncertainty issue was the distribution type used to represent input variables. Other sources that most affected model output were non-detects, unit-to-unit variability and processing. Specifying correlation between variables was found to have little effect on exposure estimates. The findings have important implications for how probabilistic modelling should be conducted, communicated and used by policy and decision makers as part of consumer risk assessment of pesticides.

Body Weight↗
PubMed1974

Microtubule biogenesis and cell shape in Ochromonas. 3. Effects of herbicidal mitotic inhibitor isopropyl N-phenylcarbamate on shape and flagellum regeneration.

The role of microtubules and microtubule nucleating sites in the unicell, Ochromonas has been examined through the use of two mitotic inhibitors, isopropyl N-phenylcarbamate (IPC) and isopropyl N-3-chlorophenyl carbamate (CIPC). Although IPC and CIPC have little or no effect on intact microtubules, the assembly of three separate sets of microtubules in Ochromonas has been found to be differentially affected by IPC and CIPC. The assembly of flagellar microtubules after mechanical deflagellation is partially inhibited; the reassembly of rhizoplast microtubules after pressure depolymerization is totally inhibited (however, macrotubules may form at the sites of microtubule initiation or elsewhere); and, the reassembly of the beak set of microtubules after pressure depolymerization may be unaffected although similar concentrations of IPC and CICP completely inhibit microtubule regeneration on the rhizoplast. These effects on microtubule assembly, either inhibitory or macrotubule inducing, are fully reversible. The kinetics of inhibition and reversal are found to be generally similar for both flagellar and cell shape regeneration. Incorporation data suggest that neither IPC nor CIPC has significant effects on protein synthesis in short term experiments. Conversely, inhibiting protein synthesis with cycloheximide has little effect on microtubule regeneration when IPC or CIPC is removed. Although the exact target for IPC and CIPC action remains uncertain, the available evidence suggests that the microtubule protein pool or the microtubule nucleating sites are specifically and reversibly affected. Comparative experiments using the mitotic inhibitor colchicine indicate some similarities and differences in its mode of action with respect to that of IPC and CIPC on assembly and disassembly of microtubules in these cells.

Amino Acids↗
PubMed1982

Cell cycle specificity of certain antimicrotubular drugs in Schizosaccharomyces pombe.

Of the seven antimicrotubular drugs tested, nocodazole, mebendazole and trifluralin at saturable concentrations failed to inhibit cell division in Schizosaccharomyces pombe, while carbendazim, thiabendazole and chloropropham each at 50 micrograms ml- and amiprophos methyl at 200 micrograms ml-1 completely arrested cell division. This inhibition was associated with striking morphological changes in which carbendazim- and thiabendazole-treated cells became elongated and pseudohyphal, whereas chloropropham- and amiprophos methyl-treated cells appeared small and rounded with occasional V-shaped pairs. Lomofungin staining revealed that nuclear division was also arrested by these drugs. Suspected blockage of defined cell cycle stages was confirmed by pulse-induction experiments which revealed that cells could be synchronized into division using exposure to a drug for one generation. Further experiments with synchronous cultures prepared by size selection showed that different drugs possessed different transition points; for example, carbendazim and thiabendazole were effective in blocking a late stage of the cell cycle just prior to division, whereas amiprophos methyl affected a very early stage. The results suggest that some of the drugs used exert cell cycle specificity in S. pombe either by impairing microtubule assembly mechanisms (as with carbendazim and thiabendazole) or by inhibiting synthesis of tubulin subunits (as with amiprophos methyl). These drugs could prove useful in studies of microtubule biogenesis during the cell cycle in yeast.

Ascomycota↗
PubMed1990

The role of microfilaments and microtubules in apical growth and dimorphism of Candida albicans.

Cytoskeleton inhibitors were used to study morphogenesis in the pathogenic and dimorphic fungus Candida albicans. Nocodazole is a specific microtubule inhibitor and chloropropham (CIPC), at high concentrations, is an inhibitor of microtubules and microfilaments. Distribution of microtubules and microfilaments was studied by immunofluorescence techniques using anti-tubulin antibody with FITC-conjugated secondary antibody, and by staining with Rh-phalloidin. Nocodazole did not arrest apical cell elongation at a concentration (20 micrograms ml-1) that inhibited nuclear division and migration. Cytoplasmic and nuclear microtubules disappeared within 30 min in filamentous cells under these conditions. However, the Rh-phalloidin-stained actin granules which were localized in the tips of filamentous cells, and the microfilaments, were arranged normally at this concentration of nocodazole. Growth, and normal distribution of microtubules and microfilaments, were inhibited by a high concentration (200 micrograms ml-1) of CIPC. At a concentration (100 micrograms ml-1) of CIPC that permitted nuclear division, apical cell elongation was arrested, and filamentous growth was converted into yeast growth. At this concentration of CIPC, microtubules were distributed normally in filamentous cells. Long microfilaments were not observed, and actin granules did not localize in the tips of filamentous cells, but were distributed throughout the cytoplasmic cortex. Our results show that cytoplasmic microtubules are not essential for the elongation of filamentous cell tips but that microfilaments are apparently essential for this process.

Actin Cytoskeleton↗