Mustard Gas or Sulfur Mustard: An Old Chemical Agent as a New Terrorist Threat

Wattana, Monica K.; Bey, Tareg

doi:10.1017/s1049023x0000649x

Cited by 113 publications

(118 citation statements)

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“…Since its first use in World War I, SM has been used in numerous conflicts worldwide including the IranIraq war between 1983 and 1988 causing more than 100,000 injuries, 30,000 of whom are still suffering from exposure (Balali-Mood and Hefazi, 2005;Balali-Mood et al, 2008;Ghanei et al, 2010). Nowadays, SM remains a threat to both military and civilian populations as a potential terrorist weapon (Wattana and Bey, 2009) because of its relatively easy synthesis, existing stockpile and the lack of effective countermeasures against its toxicity.…”

Section: Introductionmentioning

confidence: 99%

Time course of skin features and inflammatory biomarkers after liquid sulfur mustard exposure in SKH-1 hairless mice

et al. 2015

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Section: Introductionmentioning

confidence: 99%

Time course of skin features and inflammatory biomarkers after liquid sulfur mustard exposure in SKH-1 hairless mice

et al. 2015

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“…8 Furthermore, because it is relatively simple to synthesize and maintain, the potential terrorist use of SM is a present threat. 9 Therefore, understanding the effects of SM requires urgent attention.…”

Section: ■ Introductionmentioning

confidence: 99%

Analysis of Different Fates of DNA Adducts in Adipocytes Post-sulfur Mustard Exposure in Vitro and in Vivo Using a Simultaneous UPLC-MS/MS Quantification Method

Wang

Zhang

Chen

et al. 2015

Chem. Res. Toxicol.

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Sulfur mustard (SM) is a powerful alkylating vesicant that can rapidly penetrate skin, ocular, and lung bronchus mucous membranes and react with numerous nucleophiles in vivo. Although the lesion mechanisms of SM remain unclear, DNA damage is believed to be the most crucial factor in initiating SM-induced toxicity. Four major DNA adducts were identified for retrospective detection and DNA lesion evaluation, namely, N(7)-[2-[(2-hydroxyethyl)thio]-ethyl]guanine (N(7)-HETEG), bis(2-ethyl-N(7)-guanine)thioether (Bis-G), N(3)-(2-hydroxyethylthioethyl)-2'-adenine (N(3)-HETEA), and O(6)-[2-[(2-hydroxyethyl)thio]-ethyl]guanine (O(6)-HETEG). Because of previous observations that the levels of SM-DNA adducts were relatively higher in adipose-rich organs, such as the brain, we focused on the in vitro and in vivo fates of the DNA adducts in exposed adipocytes. A UPLC-MS/MS method developed in our laboratory was used to profile the N(7)-HETEG, Bis-G, and N(3)-HETEA levels in human mature adipocytes (HA-s) that had differentiated from human subcutaneous preadipocytes (HPA-s). This method was also used to profile three other cell lines related to the targeting of major tissues, including human keratinocytes (HaCaT), human hepatocytes (L-02), and human lung fibroblasts (HLF). Long-lasting adduct persistence and a high proportion of Bis-G were found in exposed adipocytes in vitro. The survival properties of exposed adipocytes were also tested. At the same time, the fate of SM-DNA adducts in vivo was characterized using a rat model exposed to 1 and 10 mg/kg doses of SM. The level of DNA adducts in the exposed adipose tissue (AT) was much lower than those in other organs studied in our previous work. The adduct persistence behavior was observed in AT with an extremely high proportion of Bis-G, which was higher than N(7)-HETEG. In light of these results, we suggest that an adipose-rich environment may promote the formation of Bis-G and that adipocyte-specific DNA repair mechanisms may result in adduct persistence and the survival of adipocytes after SM exposure. These conclusions should be further investigated.

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“…Sulfur mustard (2,2-dichlorodiethyl) sulfide is considered a likely agent to be used by terrorists. 3 Components for its synthesis are inexpensive, and the synthetic protocol is relatively easy. In addition, as a warfare agent, SM is extremely effective because even mild ocular exposures cause visual disturbances, panic, and a fear of blindness that cannot be underestimated.…”

mentioning

confidence: 99%

Doxycycline Hydrogels as a Potential Therapy for Ocular Vesicant Injury

Gordon

Desantis

Deshmukh

et al. 2010

Journal of Ocular Pharmacology and Therapeutics

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Purpose: The goals of this study were (1) to compare the injury at the basement membrane zone (BMZ) of rabbit corneal organ cultures exposed to half mustard (2 chloroethyl ethyl sulfide, CEES) and nitrogen mustard with that of in vivo rabbit eyes exposed to sulfur mustard (SM); (2) to test the efficacy of 4 tetracycline derivatives in attenuating vesicant-induced BMZ disruption in the 24-h period postexposure; and (3) to use the most effective tetracycline derivative to compare the improvement of injury when the drug is delivered as drops or hydrogels to eyes exposed in vivo to SM. Methods: Histological analysis of hematoxylin and eosin-stained sections was performed; the ultrastructure of the corneal BMZ was evaluated by transmission electron microscopy; matrix metalloproteinase-9 was assessed by immunofluorescence; doxycycline as drops or a hydrogel was applied daily for 28 days to eyes exposed in vivo to SM. Corneal edema was assessed by pachymetry and the extent of neovascularization was graded by length of longest vessel in each quadrant. Results: Injury to the BMZ was highly similar with all vesicants, but varied in degree of severity. The effectiveness of the 4 drugs in retaining BMZ integrity did not correlate with their ability to attenuate matrix metalloproteinase-9 expression at the epithelial-stromal border. Doxycycline was most effective on organ cultures; therefore, it was applied as drops or a hydrogel to rabbit corneas exposed in vivo to SM. Eyes were examined at 1, 3, 7, and 28 days after exposure. At 7 and 28 days after SM exposure, eyes treated with doxycycline were greatly improved over those that received no therapy. Corneal thickness decreased somewhat faster using doxycycline drops, whereas the hydrogel formulation decreased the incidence of neovascularization. Conclusions: Corneal cultures exposed to 2-chloroethyl ethyl sulfide and nitrogen mustard were effective models to simulate in vivo SM exposures. Doxycycline as drops and hydrogels ameliorated vesicant injury. With in vivo exposed animals, the drops reduced edema faster than the hydrogels, but use of the hydrogels significantly reduced neovascularization. The data provide proof of principle that a hydrogel formulation of doxycycline as a daily therapy for ocular vesicant injury should be further investigated.

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Mustard Gas or Sulfur Mustard: An Old Chemical Agent as a New Terrorist Threat

Cited by 113 publications

References 50 publications

Time course of skin features and inflammatory biomarkers after liquid sulfur mustard exposure in SKH-1 hairless mice

Time course of skin features and inflammatory biomarkers after liquid sulfur mustard exposure in SKH-1 hairless mice

Analysis of Different Fates of DNA Adducts in Adipocytes Post-sulfur Mustard Exposure in Vitro and in Vivo Using a Simultaneous UPLC-MS/MS Quantification Method

Doxycycline Hydrogels as a Potential Therapy for Ocular Vesicant Injury

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