Study On Biological Monitoring Of Exposure To Sulfur Mustard

Sulfur mustard (SM) is a vesicant agent, which was first used in World War I (WW I ) and was also used by Iraq during the Iran-Iraq conflict. It was reported that about 80% of the chemical casualties in WW I was caused by sulfur mustard. So it was called "king of war gases". Today, Human have to face severe terrorism threat coming from various manner included SM as a threat agent, because it is easy to prepare SM, and many countries still maintain large stockpiles of the agent up to now.The biology and toxicology of sulfur mustard in human body is complex. Sulfur mustard is a bifunctional alkylating a gent that reacts r apidly with nucleophiles under physiological conditions. These reactions in the human body include the alkylation of DNA, RNA, proteins, and glutathione. Until now the biochemical mechanism of tissue injury from SM was not well understood, DNA alkylation seems to be the most important metabolic effects.There is of increasing interest in the biomonitoring of exposure to sulfur mustard in recent years. Since its toxicities are thought to be initiated by DNA alkylation, the level of DNA damage could serve as a biomarker for exposure to SM.The aim of this study was to provide unambiguous identification and determination method of the major DNA modification produced by sulfur mustard using modern chromatographic and mass spectrometric technique. The methods described in this paper will be useful for diagnostic and therapeutic applications.First, the major adduct N7- (2-hydroxyethylthioethyl) guanine(HETEG) was synthesized and characterized. It was synthesized from the reactions of sulfur mustard with Guanosine monophosphate (GMP). After isolated and purified by Sepharose Fast Flow ion chromatography, the N7-alkylated GMP was depurinated to give the product HETEG. The yield was 17.8%. Its purity was up to 98.5% by HPLC analysis. It was...