Sulfur mustards genotoxicity

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... 

The genotoxicity of sulfur mustard is well documented. It is known to produce DNA cross-hnks, mutations following replication or repair errors, chromosomal breaks, and chromosomal aberrations. Occupational exposures have been associated with increased frequencies of somatic cell mutations, sister chromatid exchanges, and chromosome abnormalities. Studies with rats indicate that subchronic inhalation or oral exposures can produce dominant lethal 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). 

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 genotoxicity 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. 

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