N7-(2-hydroxyethylthioethyl)-guanine: a novel urinary metabolite following exposure to sulphur mustard


Sulphur mustard is a primary carcinogenic, cytotoxic and strongly vesicant agent which has been used as a chemical warfare agent since World War I. We are engaged in the development of detection methods for retrospective confirmation of sulphur mustard exposure. In previous papers we described the immunochemical detection of the major adduct formed between sulphur mustard and DNA, N7-(2-hydroxyethylthioethyl)-2@-deoxyguanosine (Fidder et al. 1994; Van der Schans et al. 1994), and the mass spectrometric detection of haemoglobin-sulphur mustard adducts (Fidder et al. 1996; Noort et al., 1996a, b). We report here on the detection of N7-(2-hydroxyethylthioethyl)guanine (N7-HETE-Gua) in urine, after exposure of guinea-pigs to sulphur mustard. Several urinary metabolites of sulphur mustard have been described in the literature. Black et al. (1992) identified a large number of urinary metabolites resulting from hydrolysis, oxidation and/or glutathione conjugation of the agent. Sandelowsky et al. (1992) showed the presence of N1-(2-hydroxyethylthioethyl)-4-imidazole in urine, which is presumably a degradation product of histidine alkylated by sulphur mustard. However, urinary metabolites derived from DNA alkylation have not yet been reported. Since the presence of several N7-alkylguanines in urine has been reported (Cushnir et al. 1993), most probably as a result of the repair of DNA damage, we investigated whether N7-

DOI: 10.1007/s002040050350

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@article{Fidder1996N72hydroxyethylthioethylguanineAN, title={N7-(2-hydroxyethylthioethyl)-guanine: a novel urinary metabolite following exposure to sulphur mustard}, author={Alex Fidder and Daan Noort and Leo P. De Jong and Hendrik P. Benschop and Albert G. Hulst}, journal={Archives of Toxicology}, year={1996}, volume={70}, pages={854-855} }