Sulfur mustards apoptosis

Kan, R.K., Pleva, C.M., Hamilton, T.A., Anderson, D.R., Petrali, J.P. (2003). Sulfur mustard-induced apoptosis in hairless guinea pig skin. Toxicol. Pathol. 31 185-90. 

Rosenthal, D.S., Velena, A. et al. (2003). Expression of dominantnegative Fas-associated death domain blocks human kerati-noc 4e apoptosis and vesication induced by sulfur mustard. J. Biol. Chem. 278 8531 0. 

Calmodulin, poly(ADP-ribose)polymerase and p53 are targets for modulating the effects of sulfur mustard (Rosenthal et al, 2000). It was tested whether calmodulin mediates the mitoehondrial apoptotic pathway induced by SM in human keratinoeytes. Of the three human CaM genes, the predominant form expressed was CaMl. These results indicate that CaM, ealeineurin, and Bad also play a role in SM-induced apoptosis, and may therefore be targets for therapeutic intervention to reduce SM injury (Simbulan-Rosenthal et al, 2006). 

Dabrowska, M.I., Becks, L.L., Lelli, J.L., Jr., Levee, M.G., Hinsbaw, D.B. (1996). Sulfur mustard induces apoptosis and necrosis in endotbelial cells. Toxicol. Appl. Pharmacol. 141 568-83. 

Steinritz, D., Emmler, J., Hintz, M., Worek, F., Kreppel, H., Szinicz, L., Kehe, K. (2007). Apoptosis in sulfur mustard treated A549 cell cultures. Life Sci. 80 2199-2201. 

Rosenthal DS, Simbulan-Rosenthal CM, Iyer S, Spoonde A, Smith W, Ray R, Smulson ME. 1998. Sulfur mustard induces markers of terminal differentiation and apoptosis in keratinoc3des via a Ca -cahnodulin and caspase-dependent pathway. J Invest Dermatol 111 64—71. 

Levitt, J.M., Lodhi, I.J., Nguyen, P.K., Ngo, V., Clift, R., Hinshaw, D.B., and Sweeney, J.F. (2003). Low-dose sulfur mustards primes oxidative function and induces apoptosis in human polymorphonuclear leukocytes. Int Immunopharmacol 3, 747-56. 

Smith KJ, Graham JS, Hamilton TA et al. (1997). Immunohistochemical studies of basement membrane proteins and proliferation and apoptosis markers in sulfur mustard induced cutaneous lesions in weanling pigs. J Dermatol Sci, 15, 173-182. 

A key component of sulfur mustard toxicity is the formation of a sulfonium ion and resulting episulfonium intermediate that may react with sulfhydryl-containing macromolecules. Damage may include Ca + translo-cases (Ca +-stimulated, Mg -dependent ATPase), which depend on thiol groups to maintain cellular Ca + homeostasis, and microfilamentous proteins. The resulting increase in intracellular calcium levels ultimately causes a decrease in cellular integrity and induction of apoptosis. Oxidative stress in sulfur mustard toxicity has been reviewed by Smith et al. (2008). 

D. S. Rosenthal, A. Velena, F. P. Chou, R. Schlegel, R. Ray, B. Benton, D. Anderson, W. J. Smith and C. M. Simbulan-Rosenthal, Expression of dominant-negative Fas-associated death domain blocks human kera-tinocyte apoptosis and vesication induced by sulfur mustard, /. Biol Chem., 2003,278, 8531-8540. 

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