The incorporation of radiolabelled sulphur from captan into protein and its impact on a DNA binding study

Provan, W. M. and Eyton-Jones, H. and Lappin, G. and Pritchard, D. and Moore, R. B. and Green, T. (1995) The incorporation of radiolabelled sulphur from captan into protein and its impact on a DNA binding study. Chemico-Biological Interactions, 96 (2). pp. 173-184. ISSN 0009-2797

Full content URL: http://dx.doi.org/10.1016/0009-2797(94)03592-V

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Item Type:Article
Item Status:Live Archive

Abstract

Repeated administration of high doses of captan is known to produce tumours specifically in the duodenum of mice. Captan is not carcinogenic in the rat. In this study, DNA purified from the liver, stomach, duodenum and jejenum of mice dosed with 35S radiolabelled captan was found to contain radioactivity equivalent to Covalent Binding Indices in the range 38-91; that from the bone marrow had a CBI of 2.8. The distribution of radioactivity between the various tissues did not reflect the target organ specificity of captan. Attempts to further purify the DNA samples using caesium chloride gradients resulted in partial separation of the radioactivity from the DNA suggesting that covalent binding to the DNA may not have occurred. A study of the chemical breakdown of captan showed that captan is unstable, producing a variety of potentially reactive species containing sulphur. Evidence was further obtained to show that the sulphur of captan is incorporated into endogenous amino acids and protein. Hepatic DNA from mice dosed with 35S radiolabelled N-acetylcysteine, and two thiazolidine derivatives which are analogous to known metabolites of captan, was radiolabelled to a similar extent to that from captan treated mice. Furthermore, the DNA from each of these treatments had similar properties on caesium chloride gradients. It was concluded that the radioactivity associated with DNA in the captan DNA binding study was present in the low levels of protein which are always associated with purified DNA samples.

Keywords:2 oxothiazolidine 4 carbyxulate cysteine, 2 thiooxothiazolidine 4 carboxylate, acetylcysteine, amino acid, captan, dna, protein, sulfur 35, thiazolidine derivative, unclassified drug, animal experiment, animal tissue, article, biodegradation, bone marrow, controlled study, covalent bond, dna binding, duodenum, jejunum, liver, male, mouse, nonhuman, protein synthesis, stomach, tissue distribution, Acetylcysteine, Animal, Cesium, Chlorides, Chromatography, High Pressure Liquid, DNA-Binding Proteins, Isotope Labeling, Mice, Proteins, Sulfur Radioisotopes, Ultracentrifugation
Divisions:College of Science > School of Pharmacy
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ID Code:8248
Deposited On:23 Mar 2013 10:19

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