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-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.
Fidder
A
A
TNO Prins Maurits Laboratory, Rijswijk, The Netherlands.
Moes
G W
GW
Scheffer
A G
AG
van der Schans
G P
GP
Baan
R A
RA
de Jong
L P
LP
Benschop
H P
HP
D000818:Animals; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000097:blood / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007962:Leukocytes / Q000737:chemistry; D009151:Mustard Gas / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000378:metabolism*; D013950:Thymus Gland / Q000737:chemistry
D004247:DNA; D009151:Mustard Gas