Synthesis, Characterization, and Quantitation of the Major Adducts Formed between Sulfur Mustard and DNA of Calf Thymus and Human Blood

Synthesis, Characterization, and Quantitation of the Major Adducts Formed between Sulfur Mustard and DNA of Calf Thymus and Human Blood

As part of a program to develop methods for verification of alleged exposure to sulfur mustard, we synthesized and characterized the adducts most likely formed by alkylation of DNA with sulfur mustard: N7-[2-[(2-hydroxyethyl)thio]ethyl]guanine (1), bis[2-(guanin-7-yl)ethyl] sulfide (2), N3-[2-[(2-hy...

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Bibliographic Details
Published in:Chemical research in toxicology Vol. 7; no. 2; pp. 199 - 204
Main Authors: Fidder, Alex, Moes, Gerrit W. H, Scheffer, Annehieke G, van der Schans, Govert P, Baan, Robert A, de Jong, Leo P. A, Benschop, Hendrik P
Format: Journal Article
Language:English
Published: Washington, DC American Chemical Society 01-03-1994
Subjects:
Animals
Biological and medical sciences
Cattle
Chemical and industrial products toxicology. Toxic occupational diseases
Chromatography, High Pressure Liquid
DNA - blood
DNA - metabolism
Humans
In Vitro Techniques
Leukocytes - chemistry
Medical sciences
Mustard Gas - analogs & derivatives
Mustard Gas - chemical synthesis
Mustard Gas - metabolism
Thymus Gland - chemistry
Toxicology
Various organic compounds
Human
Thymus gland
Leukocyte
Ox
In vitro
Vertebrata
Mammalia
Animal
DNA
Nitrogen mustard
Artiodactyla
War gas
Ungulata
Molecular adduct
Structural analysis
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Summary:As part of a program to develop methods for verification of alleged exposure to sulfur mustard, we synthesized and characterized the adducts most likely formed by alkylation of DNA with sulfur mustard: N7-[2-[(2-hydroxyethyl)thio]ethyl]guanine (1), bis[2-(guanin-7-yl)ethyl] sulfide (2), N3-[2-[(2-hydroxyethyl)thio]ethyl]adenine (3), and O6-[2-[(2-hydroxyethyl)thio]ethyl]-guanine and its 2'-deoxyguanosine derivative. Incubation of double-stranded calf thymus DNA and human blood with [35S]sulfur mustard in vitro followed by enzymatic degradation of the DNA and mild depurination afforded three major radioactive peaks upon HPLC analysis. These peaks were identified as 1-3 by coelution with the synthetic markers and mass spectrometric and electronic spectra. Compound 1 appeared to be the most abundant adduct, which is in agreement with previous investigations on DNA alkylation with sulfur mustard.
Bibliography:istex:FC61B913A86E54001DE21E565DAA7B678B61535E
ark:/67375/TPS-49VKZ0GJ-N
ObjectType-Article-2
SourceType-Scholarly Journals-1
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ISSN:0893-228X
1520-5010
DOI:10.1021/tx00038a013