Sulfur mustard mutagenicity

Because of the correlation between mutagenicity and carcinogenicity, one would expect sulfur mustard to be carcinogenic on the basis of mutagenicity data alone. This expectation is borne out by carcinogenicity tests in experimental animals and by data from human exposures. The International Agency for Research on Cancer classifies sulfur mustard as one of relatively few chemical agents on which the data are adequate to show an association with the induction of cancer in humans.7... 

Rozmiarek, H., Capizzi, R.L., Papirmeister, 8., Fuhrman, W.H., and Smith, W.J. Mutagenic activity in somatic and germ cells following chronic inhalation of sulfur mustard. Mutat. Res. 21 13-14, 1973. (abstract)... 

Sulfur mustard has found to be genotoxic and mutagenic in several microbial assays. The agent cansed alkylation of DNA in the yeast Saccharomyces cerevisiae (Kircher and Brendel, 1983), and... 

Stewart, D.L., E.J. Sass, L.K. Fritz and L.B. Sasser. 1989. Toxicology Studies on Lewisite and Sulfur Mustard Agents Mutagenicity of Sulfur Mustard in the Salmonella Histidine Reversion Assay. Final Report from Pacific Northwest Laboratories (PNL-6873) to U.S. Army Medical Research and Development Command, Fort Detrick, MD, AD A213102. 

In the review by Papirmeister et al. (1991), it was noted that sulfur mustard-induced cytotoxicity is dose dependent and that DNA appeared to be more sensitive to mustard-induced alkylation than are other cellular constituents. The low-dose effects of sulfur mustard are characterized by gen-otoxicity and inhibition of mitosis. The loss of cellular reproduction may be due to bifunctional alkylation that ultimately prevents normal DNA replication. It was hypothesized that monofunctional DNA damage might be responsible for low-dose mutagenic and possibly carcinogenic effects. 

Sulfur mustard has been found to be genotoxic and mutagenic in several microbial assays. The agent caused alkylation of DNA in the yeast Saccharo-myces cerevisiae (Kircher and Brendel 1983) and interstrand DNA cross-links (Venitt 1968) and inhibition of DNA synthesis (Lawley and Brookes 1965) in Escherichia coli. Using the histidine reversion assay, Stewart et al. (1989a) found that sulfur mustard induced point mutations in Salmonella typhimurium strain TA102 and frameshift mutations in TA 97 but neither type of mutation in strains TA98 and TAIOO. 

Genotoxicity. A mutagenicity study conducted by Auerbach and Robson (1947a) indicated that the potency of agent T to produce sex-linked lethal mutations in Drosophila melanogaster (fruit fly) is comparable to that of sulfur mustard (HD). 

Stewart DL, Sass EJ, Fritz LK, Sasser LB (1989a) Toxicology studies on lewisite and sulfur mustard agents mutagenicity of sulfur mustard in the Salmonella histidine reversion assay. PNL-6873 (DTIC AD A213102). Pacific Northwest Laboratories. Prepared for the U.S. Department of the Army, Medical Research and Development Command, Fort Detrick, MD. 

First, sulfur mustard, a vesicant warfare agent, was produced and used in World War I. Mustards alkylate a wide range of biologically important molecules producing c)dostatic, mutagenic, and cytotoxic effects. In 1936, just before the start of World War II, tabun was synthesized and then produced as the first nerve CWA. Nerve agents inhibit acetylcholinesterase (AChE) throughout... 

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