Toxicokinetics of sulfur mustard and its DNA-adducts in the hairless guinea pig.

  title={Toxicokinetics of sulfur mustard and its DNA-adducts in the hairless guinea pig.},
  author={Jan P. Langenberg and Govert P van der Schans and H E Spruit and Willem C. Kuijpers and Roos H. Mars-Groenendijk and H C van Dijk-Knijnenburg and Henk C. Trap and Herman P M van Helden and Hendrik P. Benschop},
  journal={Drug and chemical toxicology},
  volume={21 Suppl 1},
In order to provide a quantitative basis for pretreatment and therapy of intoxications with sulfur mustard (SM) the toxicokinetics of this agent as well as its major DNA-adduct were studied in male hairless guinea pigs for the intravenous, respiratory and percutaneous routes. The study comprised measurement of the concentration-time course of SM in blood and measurement of the concentrations of intact SM and its adduct to guanine in various tissues at several time points after administration of… Expand
DNA damage in internal organs after cutaneous exposure to sulphur mustard.
Brain and lungs were the organs with the highest level of SM-DNA adducts, followed by kidney, spleen and liver, which indicates that brain is an important target of SM following cutaneous exposures. Expand
A guanine-ethylthioethyl-glutathione adduct as a major DNA lesion in the skin and in organs of mice exposed to sulfur mustard.
The observation of the formation of N7Gua-ETE-GSH in vivo confirms the variety of damages induced by SM in DNA and provides another example of theformation of DNA adducts involving glutathione following in vivo exposure to bifunctional alkylating compounds. Expand
Accumulation of intact sulfur mustard in adipose tissue and toxicokinetics by chemical conversion and isotope-dilution liquid chromatography–tandem mass spectrometry
A sensitive method for the detection and quantification of intact SM in blood or tissues using isotope-dilution LC–MS/MS coupled with chemical conversion was developed and, by transforming highly reactive SM into stable derivative product, the real concentration of intactSM in biological samples was obtained accurately. Expand
Mass spectrometric analysis of sulfur mustard-induced biomolecular adducts: Are DNA adducts suitable biomarkers of exposure?
There is a need for advanced methods of ID-LC-MS/MS for the detection and quantitation of SM adducts, especially of long-term effects such as cancer formation. Expand
The pattern of immediate and long-term toxic effects following exposure to SM is reviewed with special references to the recent data on clinical and paraclinical investigations and management of more than 100,000 chemical war casualties incurred during the Iran-Iraq conflict. Expand
Retrospective detection of sulfur mustard exposure by mass spectrometric analysis of adducts to albumin and hemoglobin: an in vivo study.
The persistence in rats of sulfur mustard adducts to albumin and hemoglobin was studied in vivo after exposure and the decrease in adduct levels corresponded well with the half-life time of albumin in rats and with the lifetime of the rat erythrocyte. Expand
Modified immunoslotblot assay to detect hemi and sulfur mustard DNA adducts.
The aim of the presented work was to modify the van der Schans protocol for use in a field laboratory and to test the cross reactivity of the 2F8 antibody against nitrogen mustards, which was superior to SeramunGrün stain. Expand
Analysis of different fates of DNA adducts in adipocytes post-sulfur mustard exposure in vitro and in vivo using a simultaneous UPLC-MS/MS quantification method.
It is suggested that an adipose-rich environment may promote the formation of Bis-G and that adipocyte-specific DNA repair mechanisms may result in adduct persistence and the survival of adipocytes after SM exposure. Expand
Low Level Exposure to Sulfur Mustard: Development of a SOP for Analysis of Albumin Adducts and of a System for Non-Invasive Diagnosis on Skin
Abstract : The present research program aims at: 1. Development of a mass spectrometric or fluorescence-based method for retrospective detection of exposure to low doses of sulfur mustard, based onExpand
Uptake, Tissue Distribution, and Excretion of 14C-Sulfur Mustard Vapor Following Inhalation in F344 Rats and Cutaneous Exposure in Hairless Guinea Pigs
Results indicate inhaled SM is rapidly absorbed from the lung and distributed throughout the body while there is limited systemic distribution following cutaneous exposure. Expand


Biological fate of sulphur mustard in rat: toxicokinetics and disposition.
Urine was the major route of excretion of sulphur mustard and/or its metabolites, and significant high affinity of 14C-sulphur mustard for red blood cells was found in the systemic circulation, and residual 14C continued to be excreted until 4 days later. Expand
Inhalation toxicokinetics of soman stereoisomers in the atropinized guinea pig with nose-only exposure to soman vapor.
The terminal half-life observed after nose-only exposure is longer than that observed after an equitoxic iv bolus administration, which suggests the presence of a depot in the upper respiratory tract from which absorption continues after termination of the exposure. Expand
Protection by cysteine esters against chemically induced pulmonary oedema.
The selective enhancement of pulmonary CySH levels may provide a method for the protection of lungs against inhaled reactive toxicants by increasing intracellular CySH in the rat lungs after intraperitoneal injection. Expand
Hairless guinea pig bioassay model for vesicant vapor exposures.
The hairless guinea pig model, with graded HD vapor exposures, provides acceptable comparisons of responses and may be useful for measurements of irritant and cytotoxic responses of skin to other toxic vapors. Expand
The effect of sulphur mustard on glutathione levels in rat lung slices and the influence of treatment with arylthiols and cysteine esters
Following uptake of cysteine ester into lung slices Cysteine is elevated but this does not protect cellular glutathione from sulphur mustard. Expand
A simplified method of evaluating dose-effect experiments.
The method provides means for the rapid test of parallelism of two curves and easy computation of relative potency with its confidence limits and its accuracy is commensurate with the nature of dose-per cent effect data. Expand
The absorption of war gases by the nose.