Arroyo, C.M., A.J. Carmichael, and C.A. Broomfield. Could Nitrosyl Chloride Be Produced by Human Skin Keratinocytes and Sulfur Mustard? A Magnetic Resonance Study. In Vitro Toxicol. 1997. 10(2): 253-261.

sulfur mustard - 00505-60-2

It is known that alkylating processes occur after exposure to sulfur mustard (HD). Although direct alkylation of DNA and RNA has been widely described, we hypothesize additional alkylation events of potential importance in skin injury. We have determined by immunocytochemistry levels of interleukin-1 b (IL-1b ) in cultures of normal human epidermal keratinocytes (NHEK) after exposure to HD. The expression of IL-1b in NHEK was found to be related to cell culture donor age. In neonatal NHEK exposed to HD (2 mM), IL-1b response is increased. Electron paramagnetic resonance (EPR) spectroscopy was used to show the formation of EPR detectable, g=2.04, feature characteristic of iron-nitrosyl complex formation, and the generation of this induced complex by NHEK exposed to HD (1 mM for 18 hours) was blocked by Nw -Nitro-L-arginine (L-NOARG), a competitive inhibitor of nitric oxide synthase (NOS). Nitric oxide (· NO) has been implicated as the effector molecule that mediates IL-1b (Corbett et al, 1993). Our results show the release of nitric oxide during cytokine expression, IL-1b , when keratinocytes ae exposed to HD. The combination of the nitric oxide with the chloride (Cl- ) released from sulfur mustard ([ClCH₂CH₂]₂S) on cyclization to the sulfonium ion may lead to the formation of nitrosyl chloride (NOCl), a known potent alkylating agent. If NOCl is formed as a result of HD exposure, then it may play a role in the skin injury.