Sulfur mustard activation

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 Ethylene gas. Sulfur dichloride. Methylene chloride. Activated charcoal Blister agent... 

Schlager, J.J., Hart, B.W. (2000). Stress gene activity in HepG2 cells after sulfur mustard exposure. J. Appl. Toxicol. 20(5) 395 05. 

Outside of military conflicts, exposure to sulfur mustard has occurred or may occur in work environments associated with chemical weapon materiel (e.g. storage depots, demilitarization facilities, research laboratories), during emergency response operations or remediation and decontamination activities, or during treaty verification activities in support of the Chemical Weapons Convention. Chemical weapons such as the vesicants are stiU considered potential military threats and terrorist targets. The most likely route of exposure to sulfur mustard is via aerosol/vapor exposure of the skin, eyes, and respiratory tract. 

Recent work has focused on the identification of possible biomarkers of sulfur mustard exposure and injury (Buxton et al., 2000, 2001 Danne et al., 2000). More recently, the role of metalloproteinases and collagen degradation (Gerecke et al., 2005), platelet activating factor (Clark et al., 2005, 2006), and interaction with cytochrome P450... 

In addition to the acute toxic effects on the eyes, skin, and respiratory tract, both acute and longer-term neuropsychiatric effects (e.g. depression, anxiety, neurasthenia, insomnia, post-traumatic stress syndrome) have been documented for individuals exposed to sulfur mustard (Romano et al, 2008). Many of these effects have been documented for individuals exposed during noncombat (e.g. munitions plant workers) activities and are not always the result of high-level exposure that result in serious overt effects. Longer-term effects such as chronic bronchitis have been associated with occupational exposures that included episodes of acute toxicity, and delayed or recurrent keratitis may occur 8-40 years after a severe vapor exposure. Sulfur mustard-induced immunosuppression resulting in greater susceptibility to infections has also been reported. 

Clark, O.E., Neally, E.W., Leiter, K., Miller, A.L., Nicholson, J.D., Smith, W.J. (2006). Endothelial cell alterations following in vitro exposure to sulfur mustard or platelet activating factor. Toxicologist 90 391. 

Gerecke, D.R., Bhatt, P., Chang, Y. et. al. (2005). The matrix metalloproteinase inhibitor GM 1489 reduces MMp-9 activity after sulfur mustard exposure in vivo. Toxicologist 84 (S-1) 451. 

Smith, W.J., Cowan, F.M., Broomfield, C.A. (1991). Increased proteolytic activity in human epithelial cells following exposure to sulfur mustard. FASEB J. 5 A828. 

Casillas, R., Kam, C.M., Powers, J.C. (2000a). Serine and cysteine proteases in sulfur mustard-exposed hairless mouse skin enzymatic activity and inhibition profiles. J. Toxicol. Cutan. Ocul. Toxicol. 19 137-51. 

Gerecke, D.R., Bhatt, P. et al. (2004). Sulfur mustard alters laminin 5 and gelatinase MNRA levels and increases gelati-nase activity in a mouse ear vesicant model. Proceedings of the 43rd Annual Meeting of the Society of Toxicology, Baltimore, MD, 1888 pp. 

Hinshaw, D.B., Lodhi, I.J., Hurley, L.L., Atkins, K.B., Dabrowska, M.I. (1999). Activation of poly [ADP-ribose] polymerase in endothelial cells and keratinocytes role in an in vitro model of sulfur mustard-mediated vesication. Toxicol. Appl. Pharmacol. 156 17-29. 

Kam, C.M., Selzler, J., Schulz, S.M. (1997). Enhanced serine protease activities in the sulfur mustard-exposed homogenates of hairless guinea pig skin. Int. J. Toxicol. 16 625-38. 

Kehe, K., Rupee, R., Thiermann, H. (2008). Activation of NFKB and mitogen-activated protein kinase pathways in keratino-c 4es after sulfur mustard exposure. Proceedings of the U.S. Army Medical Defense Bioscience Review, Hunt Valley, MD, 145 pp. 

Woessner, J.F., Jr., Dannenherg, A.M., Jr. et al. (1990). Extracellular collagenase, proteoglycanase and products of their activity, released in organ culture by intact dermal inflammatory lesions produced by sulfur mustard. J. Invest. Dermatol. 95 717-26. 

Bhat, K.R., Benton, B.J., Ray, R. (2006). Poly (ADP-rihose) polymerase (PARP) is essential for sulfur mustard-induced DNA damage repair, hut has no role in DNA ligase activation. J. Appl. Toxicol. 26 452-7. 

Popiel, S., Witkiewicz, Z., Nalepa, T. (2005). The reactions of sulfur mustard with the active components of organic decontaminants. J. Hazard. Mater. 123 269-80. 

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