Mustard grubu kimyasal savaş ajanları ve klinik etkileri

Year 2017, Volume: 4 Issue: 4, 322 - 331, 01.12.2017

Fatih Kalkan Ömer Aykutluğ Turgut Topal

Abstract

Mustard gazı geçtiğimiz yüzyıl içerisinde en çok kullanılan, yüz binlerce insanın ölümüne ve yaralanmasına yol açan vezikan ajanlar olarak sınıflandırılan kimyasal silah grubudur. Sülfür mustard (SM) ve analoğu olan Nitrojen mustard (NM)bu gruba dahil iki kimyasal ajandır. İçinde bulunduğumuz orta doğu ve yakın coğrafyadaki İran, Irak, Libya, Suriye gibi ülkelerin elinde tonlarca sülfür mustard gazı bulunduğu ve bunun bölge ülkeleri için çok ciddi bir tehdit olduğu artık herkes tarafından bilinen bir gerçektir. Ortaya çıkardığı devasa etkiler nedeniyle mustard gazı “savaş gazlarının kralı”ünvanınıalmıştır. Tarih sürecinde ilk defa 1.Dünya Savaşı’nda kullanılmış olan mustard gazı, takip eden yıllar içerisinde defalarca silahlı mücadelelerde kullanılmış asker ve sivillerin kitlesel ölümüne ve yaralanmasına neden olmuştur. Elde edilmesi, depolanması ve kullanımı konusundaki kolaylık mustard gazının tercih edilmesinin en önemli nedenleridir. Mortaliteden çok mobiditeye neden olmasımustard gazının bir savaş ajanı olarak tercih edilmesinin diğer nedenidir. Bu nedenle devletler yıllarca yaralıların bakımıyla uğraşmış ve bu durum maddi ve manevi bir yıkıma neden olmuştur. Oldukça yüksek toksisiteye sahip olması maruz kalınan doz ile doğru orantılı olarak ani ölümleri de beraberinde getirmektedir. Başlıca etkilerini göz, akciğer ve deri üzerinde gösteren mustard gazı kanser oluşumu da dahil olmak üzere vücutta birçok hasara yol açmaktadır. Nitrojen mustard kimyasal yapısı ve oluşturmuş olduğu toksisite bakımından SM ile büyük ölçüde benzerlik göstermektedir. Oluşturmuş olduğu etkiler nedeniyle kullanımı yasaklanmıştır. Kullanımı sonrasında yaralanan kişiler üzerinde yapılan çalışmalar kemoterapötik bir ajan olarak kullanılabileceği sonucunu doğurmuştur. Antidotu bulunmayan tek kimyasal ajan olması nedeniyle yaklaşık yarım yüzyıldır üzerinde yürütülen antidot geliştirme çabaları belli bir düzeye kadar gelmiştir ancak bu konuda halen alınması gereken önemli mesafeler bulunmaktadır

Keywords

Sülfür Mustard, Nitrojen Mustard, Kimyasal silah, Toksisite

Mustard group chemical warfare agents and clinical effects

Abstract

Mustard gas is the most used chemical weapon group in the past century, which is classified as a vesicant agent
that leads to the death and injury of hundreds of thousands of people. Sulfur mustard (SM) and its analogue
Nitrogen mustard (NM) are the two chemical agents involved in this group. This is a fact known by everyone that
Iran, Iraq, Libya, Syria like countries in the middle east and close geography have tons of sulfur mustard gas in
the hands which is a serious threat to the countries of the region.
Due to the enormous effects that it has caused, mustard gas has taken the title of “king of the battle gasses”.
Mustard gas, which was used in World War I for the first time in history, has caused massive deaths and injuries of
soldiers and civilians, which have been used repeatedly in armed struggles over the following years. The convenience
of obtaining, storing and using is the most important reason why mustard gas is preferred as a waragent. More
morbidity than mortality is the another reason why it is preferred as a war agent. Because of this feature, states
have been dealing with the care of the wounded for years and have suffered material and spiritual destruction.
Having a fairly high toxicity also leads to sudden deaths in direct proportion to the exposure dose. Mustard gas,
which shows its major effects on the eyes, lungs and skin, leads to many damage to the body including cancer
formation. Mustard gas, which shows its major effects on the eyes, lungs and skin, leads to many pathological
damage in the body, including cancer. Nitrogen mustard has great similarity to SM in terms of chemical structure
and toxicity. The use of NM is prohibited after World War II, due to the effects that it has formed. Studies on
injured people after use have resulted in a possible use as a chemotherapeutic agent.
Due to the fact that it is the only chemical agent with no antidote, the efforts to develop antidote for about half a
century have reached a certain level, but there is stil considerable distance to be taken in this respect.

Keywords

SulfurMustard, NitrogenMustard, Chemicalweapon, Toxicity

References

• Hüseyin Pazarcı, (2000), Uluslararası Hukuk Dersleri, IV. Kitap, Ankara: Turhan Kitabevi, , s. 213’den M. Bothe, “Chemical Warfare”, Encyclopedia, Vol I I I , s. 83.
• Wright LK, Lee RB, Vincelli NM, Whalley CE, Lumley LA. (2015),Comparison of thelethaleffects of chemicalwarfarener veagentsacross multipleages. ToxicolLett. Nov 24.
• AgencyforToxicSubstances and DiseaseRegistry Medicalmanagementguidelinesfor HCN (2007), Retrieved; June/20/2017 Availablefrom.
• Karagama YG, Newton JR, Newbegin CJ. (2003), Short-term and long-term physical effects of exposure to CS spray. Journal of the Royal Society of Medicine.;96(4):172-4.
• Ciottone GR, Anderson PD. (2006), Disaster medicine. Philadelphia, PA: Mosby Elsevier;. xxxi, 952 p. p.
• Mechem CC HA. Incapacitating Agent,LSD May 11,2006. Retrieved; June/20/2017Available from: http://emedicine. com/emerg/topic911.htm.
• CP H. CBRNE, Incapacitating Agent, 3 Quinuclidinyl Benzilate May 24,2006.Retrieved; June/20/2017 Available from: http:// emedicine.com/emerg/topic912.htm.
• Beck NV, Carrick WA, Cooper DB, Muir B. (2001) Extraction of thiodiglycol from soil using pressurised liquid extraction. Journal of chromatography A., 907(1-2):221-7.
• Medvedeva N, Polyak Y, Kuzikova I, Orlova O, Zharikov G. (2008) The effect of mustard gas on the biological activity of soil. Environmental research, 106(3):289-95.
• Saladi RN, Smith E, Persaud AN. (2006) Mustard: a potential agent of chemical warfare and terrorism. Clinical and experimental dermatology, 31(1):1-5.
• Levine AL, Richie PJ. (1989) Urological complications of cyclophosphamide.J Urol., 141:1063–9.
• T. Tadmor and A. Polliack, (2012),“Optimal management of older patients with chronic lymphocytic leukemia: some facts and principles guiding therapeutic choices,” Blood Reviews, vol. 26, no. 1, pp. 15–23
• Shanbrom, Edward, et al.(1960) “Therapeutic Spectrum of Uracil-Mustard, A New Oral Antitumor Drug: With Special Reference to the Effects of Small Dosage in Lymphomas, Chronic Leukemias, and Ovarian Carcinoma.”JAMA 174.13: 1702-1705.
• Souhami RL, TannockI, Hohenberger P, Horiot J-C, Hartley JA; Souhami RL, Tannock I, Hohenberger P, Horiot J-C, editors. (2002), Alkylating agents. Oxford Textbook of Oncology. 2nd ed. Oxford University Press; Oxford, United Kingdom; p. 639-654
• West CJ (1919), The History of Poison Gases. Science.49(1270):412-7.
• Goodwin B. (1998) Keen as mustard : Britain’s horrific chemical warfare experiments in Australia. St Lucia, Qld., Australia: University of Queensland Press;. xviii, 361 p., 20 p. of plates p.
• JACQUES J. (1991) LES PREMIERES VICTIMES DE L’YPERITE. New journal of chemistry.;15(1):3-4.
• Wa l t o n L P, M a y n a r d R L , M u r r a y V S G. 1 9 9 6 Retrieved;16.02.2016, Available from: http://www.inchem. org/documents/pims/chemical/mustardg.htm.
• Bismuth C, Borron SW, Baud FJ, Barriot P. (2004) Chemical weapons: documented use and compounds on the horizon. Toxicology letters.149(1-3):11-8.
• Marshall VC. (1987), Major chemical hazards. Medium: X; Size: Pages: 600 p.
• Pearson, Graham S. (2010), “Uses of CW since the First World War”. Federation of American Scientitst Retrieved -06-28.
• Khateri S, Ghanei M, Keshavarz S, Soroush M, Haines D. (2003), Incidence of lung, eye, and skin lesions as late complications in 34,000 Iranians with wartime exposure to mustard agent. Journal of occupational and environmental medicine / American College of Occupational and Environmental Medicine, 45 (11):1136-43.
• Davison C, Rozman RS, Smith PK. (1961), Metabolism of bis- beta-chloroethyl sulfide (sulfur mustard gas). Biochemical pharmacology.7:65-74.
• Ghabili K, Agutter PS, Ghanei M, Ansarin K, Shoja MM. (2010), Mustard gas toxicity: the acute and chronic pathological effects. Journal of applied toxicology : JAT.;30(7):627-43.
• Ghanei M, Harandi AA. (2007), Long term consequences from exposure to sulfur mustard: a review. Inhalation toxicology.19(5):451-6.
• Yaren H, Mollaoglu H, Kurt B, Korkmaz A, Oter S, Topal T, et al. (2007), Lung toxicity of nitrogen mustard may be mediated by nitric oxide and peroxynitrite in rats. Research in veterinary science.;83 (1):116-22.
• Etezad-Razavi M, Mahmoudi M, Hefazi M, Balali-Mood M. (2006), Delayed ocular complications of mustard gas poisoning and the relationship with respiratory and cutaneous complications. Clinical & experimental ophthalmology.34(4):342-6.
• Ghasemi H, Ghazanfari T, Babaei M, Soroush MR, Yaraee R, Ghassemi-Broumand M, et al. (2008), Long-term ocular complications of sulfur mustard in the civilian victims of Sardasht, Iran. Cutaneous and ocular toxicology. 27(4):317- 26.
• Ghasemi H,Ghazanfari T, Ghassemi-Broumand M, Javadi MA, Babaei M, Soroush MR, Yaraee R, Faghihzadeh S,Poorfarzam S, Owlia P, (2008), Long-term ocular complications of sülfür mustard in the civilian victims of Sardasht,Iran.Cutan.Ocul.Toxicoloc.27:317-326
• Khateri S, Ghanei M, Keshavarz S, Soroush M, Haines D. (2003), Incidence of lung, eye, and skin lesions as late complications in 34,000 Iranians with wartime exposure to mustard agent. Journal of occupational and environmental medicine / American College of Occupational and Environmental Medicine, 45(11):1136-43.
• Balali-Mood M, Hefazi M, Mahmoudi M, Jalali E, Attaran D, Maleki M, et al. (2005), Long-term complications of sulphur mustard poisoning in severely intoxicated Iranian veterans. Fundamental & clinical pharmacology.;19(6):713-21.
• Marshall SLA. (1964), American Heritage History of World War I. New York: NY: Simon and Schuster;: 167.
• Requena L, Requena C, Sanchez M, Jaqueti G, Aguilar A, Sanchez-Yus E, et al.(1988), Chemical warfare. Cutaneous lesions from mustard gas. Journal of the American Academy of Dermatology.;19(3):529-36.
• Kan RK, Pleva CM, Hamilton TA, Anderson DR, Petrali JP. (2003), Sulfur mustard-induced apoptosis in hairless guinea pig skin. Toxicologic pathology. 31(2):185-90.
• Kehe K, Balszuweit F, Steinritz D, Thiermann H. (2009), Molecular toxicology of sulfur mustard-induced cutaneous inflammation and blistering. Toxicology, 263(1):12-9.
• Shakarjian MP, Heck DE, Gray JP, Sinko PJ, Gordon MK, Casillas RP, et al. (2010), Mechanisms mediating the vesicant actions of sulfur mustard after cutaneous exposure. Toxicological sciences : an official journal of the Society of Toxicology.;114(1):5-19.
• Chilcott RP, Jenner J, Carrick W, Hotchkiss SA, Rice P. (2000), Human skin absorption of Bis-2-(chloroethyl)sulphide (sulphur mustard) in vitro. Journal of applied toxicology : JAT.20(5):349-55.
• Hefazi M, Maleki M, Mahmoudi M, Tabatabaee A, Balali- Mood M. (2006), Delayed complications of sulfur mustard poisoning in the skin and the immune system of Iranian veterans 16-20 years after exposure. International journal of dermatology.;45(9):1025-31.
• Shirazi S, Balali-Mood M, editors. (1988), Comparison of early and late toxic effects of sulfur mustard poisoning in a two-year period. The First International Medical Congress on Chemical Warfare Agents in Iran Mashhad, Iran: Mashhad University of Medical Sciences
• Emad A, Rezaian GR. (1997), The diversity of the effects of sulfur mustard gas inhalation on respiratory system 10 years after a single, heavy exposure: analysis of 197 cases. Chest.112(3):734-8.
• Inada S, Hiragun K, Seo K, Yamura T. (1978), Multiple Bowen’s disease observed in former workers of a poison gas factory in Japan, with special reference to mustard gas exposure. The Journal of dermatology, 5(2):49-60.
• Photographs: Willems JL. (1989), Clinical management of mustard gas casualties. Ann Med Milit Belg.3S:14, 15
• Hosseini K, Moradi A, Mansouri A, Vessal K. (1989) Pulmonary manifestations of mustard gas injury: a review of 61 cases. Iran J Med Sci.14:20-6.
• AR D. (1990), Contemporary issues in Toxicology Dose Concepts for Inhaled Vapors and Gases. Toxicology and applied pharmacology. (103):185-97.
• Foroutan S. (1997) Medical notes concerning chemical warfare V [original in Farsi]. Kowsar Medical Journal.2.
• Greenfield RA, Brown BR, Hutchins JB, Iandolo JJ, Jackson R, Slater LN, et al. (2002), Microbiological, biological, and chemical weapons of warfare and terrorism. The American journal of the medical sciences.323(6):326-40.
• Emad A, Rezaian GR. (1997), The diversity of the effects of sulfur mustard gas inhalation on respiratory system 10 years after a single, heavy exposure: analysis of 197 cases. CHEST Journal. 112(3):734-8.
• Ghanei M, Akbari Moqadam F, Mohammad MM, Aslani J. (2005) Tracheobronchomalacia and air trapping after mustard gas exposure. Am J Respir.Crit.Care Med. 2006 Feb 1;173(3):304-9 Oct 27.
• Hosseini-khalili A, Haines DD, Modirian E, Soroush M, Khateri S, Joshi R, et al. (2009), Mustard gas exposure and carcinogenesis of lung. Mutation research.;678(1):1-6.
• Wheeler GP. (1967), Symposium on immunosuppressive drugs. Some biochemical effects of alkylating agents. Federation proceedings;26(3):885-92.
• Graef I, Karnofsky DA, et al. (1948), The clinical and pathologic effects of the nitrogen and sulfur mustards in laboratory animals. The American journal of pathology.;24(1):1-47.
• Koletsky AJ, Bertino JR, Farber LR, Prosnitz LR, Kapp DS, Fischer D, et al. Second neoplasms in patients with Hodgkin’s disease following combined modality therapy- -the Yale experience. Journal of Clinical Oncology. 1986;4(3):311-7.
• https://www.whocc.no/atc_ddd_index/?show description= yes&code =L01AA
• Roberts J, Brent T, Crathorn A. The mechanism of the cytotoxic action of alkylating agents on mammalian cells. The interaction of drugs and subcellular components in animal cells1968;5.
• Gilman A, Philips FS. The biological actions and therapeutic applications of the B-chloroethyl amines and sulfides. Science. 1946;103(2675):409-15.
• Greene MH, Boice Jr JD, Greer BE, Blessing JA, Dembo AJ. Acute nonlymphocytic leukemia after therapy with alkylating agents for ovarian cancer: a study of five randomized clinical trials. New England Journal of Medicine. 1982;307(23):1416-21.
• Myers C, Chabner B. Cancer chemotherapy: principles and practice. Lippincott: Philadelphia; 1990. p. 256-381.
• https://www.oncolink.org/cancer-treatment/chemotherapy/ oncolink-rx/mechlorethamine-mustargen-r-nitrogen- mustard)