The role of glutathione in DNA damage by potassium bromate in vitro.
We have investigated the role of reduced glutathione (GSH) in the genetic toxicity of the rodent renal carcinogen potassium bromate (KBrO(3)). A statistically significant increase in the concentration of 8-oxodeoxyguanosine (8-oxodG) relative to deoxyguanosine was measured following incubation of calf thymus DNA with KBrO(3) and GSH or N-acetylcysteine (NACys). This was dependent on these thiols and was associated with the loss of GSH and production of oxidized glutathione. A short-lived (<6 min) intermediate was apparent which did not react with the spin trap dimethylpyrroline N-oxide. DNA oxidation was not evident when potassium chlorate (KClO(3)) or potassium iodate (KIO(3)) were used instead of KBrO(3), though GSH depletion also occurred with KIO(3), but not with KClO(3). Other reductants and thiols in combination with KBrO(3) did not cause a significant increase in DNA oxidation. DNA strand breakage was also induced by KBrO(3) in human white blood cells (5 mM) and rat kidney epithelial cells (NRK-52E, 1.5 mM). This was associated with an apparent small depletion of thiols in NRK-52E cells at 15 min and with an elevation of 8-oxodG at a delayed time of 24 h. Depletion of intra-cellular GSH by diethylmaleate in human lymphocytes decreased the amount of strand breakage induced by KBrO(3). Extracellular GSH, however, protected against DNA strand breakage by KBrO(3), possibly due to the inability of the reactive product to enter the cell. In contrast, membrane-permeant NACys enhanced KBrO(3)-induced DNA strand breakage in these cells. DNA damage by KBrO(3) is therefore largely dependent on access to intracellular GSH. (+info)
Chorioretinal diffusion processes following pigment epithelial degeneration.
We studied the effect of sodium iodate-induced pigment epithelial degeneration on chorioretinal diffusion processes. Rabbits received two intravenous injections of sodium iodate at the retinotoxic dose of 22.5 mg. per kilogram over a six- to eight-hour period. Combined horseradish peroxidase tracing technique and electron microscopy were used to compare diffusion processes over a five-week period. Ultrastructural examination of retina twenty-four hours after iodate administration revealed pigment epithelial degeneration, accompanied by disruption of junctional complexes (zonulae occludentes). Peroxidase molecules were found in areas of greater cytoplasmic degeneration and in intercellular spaces up to the level of the external limiting membrane. Ultrastructural observations at later stages revealed similar findings except in the case of Muller cells, 20 per cent of which showed cytoplasmic degeneration and peroxidase uptake. The diffusion barrier was not re-established as the replacement cells did not rebuild zonulae occludentes. (+info)
Evaluation of a scheme for the pre-distribution of stable iodine (potassium iodate) to the civilian population residing within the immediate countermeasures zone of a nuclear submarine construction facility.
BACKGROUND: The Barrow-in-Furness stable iodine (potassium iodate) tablet pre-distribution scheme was the first of its kind to be introduced to protect the population living around a fixed site nuclear facility in the United Kingdom. Pre-distribution schemes have attracted critical comment principally because the certainty of availability of potassium iodate tablets was unknown. This study aimed to establish the reliability of such a scheme. METHOD: A structured interviewer-administered survey of a random sample of households served by the pre-distribution scheme was carried out using a standardized questionnaire. RESULTS: The ability of this scheme to provide stable iodine protection declined from 100 per cent to 60 per cent coverage over a period of two years for the designed worst-case demand (the ability to supply stable iodine tablets to all household residents normally living within the pre-distribution scheme zone). CONCLUSIONS: Pre-distribution has value in areas where evacuation to a centre where stable iodine tablets are available or post-accident distribution to sheltering households is difficult. The value of such a scheme must be calculated against a predictable decline in its effectiveness. In implementing such a scheme it should be noted that this decline in coverage can be reduced by calculating the frequency with which tablet packs are redistributed to take account of this factor. (+info)
The effect of anions on azide binding to myoglobin: an unusual functional modulation.
The effect of increasing concentrations of several anions on the azide (N(-)(3)) binding properties of sperm whale and horse ferric myoglobin has been studied. Surprisingly, a number of anions may act as heterotropic effectors, decreasing the affinity of myoglobins for N(-)(3), in the following order: ClO(-)(4)=I(-)>Br(-)>Cl(-) and SO(2-)(4), which mirrors the increase in their charge density. The largest effects were measured using ClO(-)(4) and I(-), which produce a 4-fold and 8-fold reduction of the N(-)(3) binding affinity in horse and sperm whale myoglobins, respectively. A dissociation equilibrium constant (K(d)) ranging from 150 to 250 mM was estimated for ClO(-)(4) and I(-) binding to myoglobins. In order to analyse the molecular mechanism producing the reduction of the N(-)(3) binding affinity to ferric myoglobin, the potential anionic binding sites within ferric myoglobin were investigated by a molecular modelling study using the program Grid. Analysis of the theoretical results suggests two particularly favourable binding sites: the first, next to the distal side of the haem, whose occupancy might alter the electrostatic potential surrounding the bound N(-)(3); the second, involving residues of helices B and G which are far from the haem iron atom, thus implying a long range effect on the bound N(-)(3). Based on the evidence that no significant conformational changes are found in the three-dimensional structures of N(-)(3)-free and N(-)(3)-bound myoglobin and on previous results on N(-)(3) binding to ferric myoglobin mutants in CD3 positions, we favour the first hypothesis, suggesting that the functional heterotropic modulation of monomeric myoglobin is mainly depending on a decrease of the positive charge density induced by the binding of anions to the haem distal side. (+info)
Sensitive kinetic-spectrophotometric determination of iodate in iodized table salt based on its accelerating effect on the reaction of bromate with chloride ion in the presence of hydrazine.
A simple, precise, sensitive and accurate method was developed for rapid determination of trace quantities of iodate. The method is based on the accelerating effect of iodate on the reaction of bromate and chloride acid in the presence of hydrazine in acidic media. The decolorization of Methyl Orange with the reaction products was used to monitor the reaction spectrophotometrically at 525 nm. Iodate could be determined in the concentration ranges of 0.03 - 1.2 microg ml(-1). The relative standard deviation for ten replicate determinations of 0.3 microg ml(-1) of iodate was 1.65%. The proposed method was applied to the determination of iodate in table salts with satisfactory results. (+info)
Acidimetric titration of medicines being salts of weak acids and determining the end-point based on the iodate(V)-iodide reaction.
A sample being a salt of weak acid in a solvent is determined with hydrochloric acid in the presence of iodate, iodide and starch. The excess acid colours the solution blue. (+info)
Novel oxidative dimer from caffeic acid.
The novel Diels-Alder adduct, dicaffeoyl quinone as its hydrate, was formed from the oxidation of 3,4-dihydroxycinnamic acid (caffeic acid) with NaIO4. The structure of this hydrate was determined by spectroscopic methods. (+info)
Transient increase of b-wave in the mouse retina after sodium iodate injection.
Twenty C57 black mice received an injection of 40 mg/kg of sodium iodate through the caudal vein. The electroretinograms (ERGs) were recorded before and after injection. Flash stimuli with the maximum illuminance, 30,000 lux, were given at increasing levels of illuminance in 0.6 log U steps for 13 levels of intensity. The a- and b-wave amplitudes increased linearly with increased stimulus intensity for approximately 5.0 log U before being saturated. Twenty four hours after injection, the intensity-amplitude curve shifted toward the higher intensity region. It was calculated that the sensitivity loss of the b-wave after injection was 2.0 log U, although the maximum amplitude was larger and the peak latency was delayed. The same results were seen less obviously in the ERGs 48 hr after injection. After 96 hr, both waves were greatly attenuated and even abolished. At the time the increased ERGs were recorded, the histopathologic findings exhibited severe damage of the retina in the pigment epithelium and in the outer layer. (+info)