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An evidence-based review of the genotoxic and reproductive effects of sulfur mustard

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A Correction to this article was published on 12 June 2018

This article has been updated

Abstract

Sulfur mustard (SM) is a chemical warfare agent which is cytotoxic in nature, and at the molecular level, SM acts as DNA alkylating agent leading to genotoxic and reproductive effects. Mostly, the exposed areas of the body are the main targets for SM; however, it also adversely affects various tissues of the body and ultimately exhibits long-term complications including genotoxic and reproductive effects, even in the next generations. The effect of SM on reproductive system is the reason behind male infertility. The chronic genotoxic and reproductive complications of SM have been observed in the next generation, such as reproductive hormones disturbances, testicular atrophy, deficiency of sperm cells, retarded growth of sperm and male infertility. SM exerts toxic effects through various mechanisms causing reproductive dysfunction. The key mechanisms include DNA alkylation, production of reactive oxygen species (ROS) and nicotinamide adenine dinucleotide (NAD) depletion. However, the exact molecular mechanism of such long-term effects of SM is still unclear. In general, DNA damage, cell death and defects in the cell membrane are frequently observed in SM-exposed individuals. SM can activate various cellular and molecular mechanisms related to oxidative stress (OS) and inflammatory responses throughout the reproductive system, which can cause decreased spermatogenesis and impaired sperm quality via damage to tissue function and structure. Moreover, the toxic effects of SM on the reproductive system as well as the occurrence of male infertility among exposed war troopers in the late exposure phase is still uncertain. The chronic effects of SM exposure in parents can cause congenital defects in their children. In this review, we aimed to investigate chronic genotoxic and reproductive effects of SM and their molecular mechanisms in the next generations.

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Change history

  • 12 June 2018

    This is with reference to the note of the Editor-in-Chief of the Archives of Toxicology.

References

  • Abolghasemi H, Radfar MH, Rambod M, Salehi P, Ghofrani H, Soroush MR, Khademolhosseini SM (2010) Childhood physical abnormalities following paternal exposure to sulfur mustard gas in Iran: a case-control study. Confl Health 4:13. doi:10.1186/1752-1505-4-13

    Article  PubMed  PubMed Central  Google Scholar 

  • Agarwal A, Virk G, Ong C, Du Plessis SS (2014) Effect of oxidative stress on male reproduction. World J Men’s Health 32(1):1–17

    Article  Google Scholar 

  • Agin K, Sarvghadi F (2006) Serum free testosterone levels among sulfur mustard induced asthma in Iranian war veterans 15 years postwar: a case control study. Int J Endocrinol Metab 3, Summer:130–135

    Google Scholar 

  • Aguiar MJ, Campos ÂS, Aguiar RA, Lana AMA, Magalhães RL, Babeto LT (2003) Neural tube defects and associated factors among liveborn and stillborn infants. J Pediatr 79(2):129–134

    Google Scholar 

  • Amir A, Chapman S, Kadar T, Gozes Y, Sahar R, Allon N (2000a) Sulfur mustard toxicity in macrophages: effect of dexamethasone. J Appl Toxicol 20(1):S51–S58

    PubMed  CAS  Google Scholar 

  • Amir A, Turetz J, Chapman S, Fishbeine E, Meshulam J, Sahar R, Kadar T (2000b) Beneficial effects of topical anti-inflammatory drugs against sulfur mustard-induced ocular lesions in rabbits. J Appl Toxicol 20(S1):S109–S114

    Article  PubMed  CAS  Google Scholar 

  • Amirzargar MA, Yavangi M, Rahnavardi M, Jafari M, Mohseni M (2009) Chronic mustard toxicity on the testis: a historical cohort study two decades after exposure. Int J Androl 32(4):411–416

    Article  PubMed  CAS  Google Scholar 

  • Aydin O, Akyuz F, Tekin N, Ustuner M, Degirmenci I, Burukoglu D, Ozden H (2016) Effect of retinyl acetate on transglutaminase 2 activity in carcinogen treated rat liver. Biotech Histochem 91(5):342–351

    Article  PubMed  CAS  Google Scholar 

  • Azizi F, Elyasi H, Sohrabpour H, Jalali N, Nafarabadi M (1989) Serum concentrations of various hormones following exposure to chemical weapons containing sulfur mustard. Med J Islam Repub Iran 3(3):105–107

    Google Scholar 

  • Azizi F, Keshavarz A, Roshanzamir F, Nafarabadi M (1995) Reproductive function in men following exposure to chemical warfare with sulphur mustard. Med Confl Surviv 11(1):34–44

    CAS  Google Scholar 

  • Balali-Mood M, Balali-Mood B (2015) Sulphur mustard poisoning and its complications in Iranian veterans. Iran J Med Sci 34(3):155–171

    Google Scholar 

  • Balali-Mood M, Navaeian A (1986) Clinical and paraclinical findings in 233 patients with sulfur mustard poisoning. In: Paper presented at the proceedings of the second world congress on new compounds in biological and chemical warfare, Rijksuniversiteit, Ghent, pp 464–473

  • Balali-Mood M, Hefazi M, Mahmoudi M, Jalali E, Attaran D, Maleki M, Jaafari MR (2005) Long-term complications of sulphur mustard poisoning in severely intoxicated Iranian veterans. Fundam Clin Pharmacol 19(6):713–721

    Article  PubMed  CAS  Google Scholar 

  • Balali-Mood M, Mousavi S, Balali-Mood B (2008) Chronic health effects of sulphur mustard exposure with special reference to Iranian veterans. Emerg Health Threats J 1:e7. doi:10.3134/ehtj.08.007

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Batal M, Boudry I, Mouret S, Cléry-Barraud C, Wartelle J, Bérard I, Douki T (2014) DNA damage in internal organs after cutaneous exposure to sulphur mustard. Toxicol Appl Pharmacol 278(1):39–44

    Article  PubMed  CAS  Google Scholar 

  • Bujan L, Walschaerts M, Moinard N, Hennebicq S, Saias J, Brugnon F et al (2013) Impact of chemotherapy and radiotherapy for testicular germ cell tumors on spermatogenesis and sperm DNA: a multicenter prospective study from the CECOS network. Fert Stert 100(3):673–680. doi:10.1016/j.fertnstert.2013.05.018

    Article  CAS  Google Scholar 

  • Colagar AH, Marzony ET (2009) Ascorbic acid in human seminal plasma: determination and its relationship to sperm quality. J Clin Biochem Nutr 45(2):144–149

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Colagar AH, Marzony ET, Chaichi MJ (2009a) Zinc levels in seminal plasma are associated with sperm quality in fertile and infertile men. Nutr Res 29(2):82–88

    Article  PubMed  CAS  Google Scholar 

  • Colagar AH, Pouramir M, Marzony ET, Jorsaraei SGA (2009b) Relationship between seminal malondialdehyde levels and sperm quality in fertile and infertile men. Braz Arch Biol Technol 52(6):1387–1392

    Article  CAS  Google Scholar 

  • Council U (1988) Report of the mission dispatched by the secretary general to investigate allegations of the use of chemical weapons in the conflict between the Islamic Republic of Iran and Iraq. United Nations Council, New York

    Google Scholar 

  • Davis KG, Aspera G (2001) Exposure to liquid sulfur mustard. Ann Emerg Med 37(6):653–656

    Article  PubMed  CAS  Google Scholar 

  • Do-Nascimento A, De-Lima E, Boëchat G, Meyrelles S, Bissoli N, Lenz D, De-Andrade T (2015) Testosterone induces apoptosis in cardiomyocytes by increasing proapoptotic signaling involving tumor necrosis factor-α and renin angiotensin system. Hum Exp Toxicol 34(11):1139–1147

    Article  PubMed  CAS  Google Scholar 

  • Ebadi A, Moradian T, Mollahadi M, Saeed Y, Refahi AA (2014) Quality of life in Iranian chemical warfare veteran’s. Iran Red Crescent Med J 16(5):e5323. doi:10.5812/ircmj.5323

    Article  PubMed  PubMed Central  Google Scholar 

  • 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 J 112(3):734–738

    Article  CAS  Google Scholar 

  • Feister AJ (1991) Medical defense against mustard gas: toxic mechanisms and pharmacological implications. CRC Press, Boca Raton

    Google Scholar 

  • Ghabili K, Agutter PS, Ghanei M, Ansarin K, Shoja MM (2010) Mustard gas toxicity: the acute and chronic pathological effects. J Appl Toxicol 30(7):627–643

    Article  PubMed  CAS  Google Scholar 

  • Ghabili K, Agutter PS, Ghanei M, Ansarin K, Panahi Y, Shoja MM (2011) Sulfur mustard toxicity: history, chemistry, pharmacokinetics, and pharmacodynamics. Crit Rev Toxicol 41(5):384–403

    Article  PubMed  CAS  Google Scholar 

  • Ghanei M (2004) Delayed haematological complications of mustard gas. J Appl Toxicol 24(6):493–495

    Article  PubMed  CAS  Google Scholar 

  • Ghanei M, Harandi AA (2016) Mustard lung: diagnosis and treatment of respiratory disorders in sulfur-mustard injured patients. Academic Press, New York

    Google Scholar 

  • Ghanei M, Adibi I, Farhat F, Aslani J (2008) Late respiratory effects of sulfur mustard: How is the early symptoms severity involved? Chron Respir Dis 5(2):95–100

    Article  PubMed  CAS  Google Scholar 

  • Graham JS, Chilcott RP, Rice P, Milner SM, Hurst CG, Maliner BI (2005) Wound healing of cutaneous sulfur mustard injuries: strategies for the development of improved therapies. J Bums Wounds (serial line) 4(1):1. http://www.joumalofbumsandwounds.com

  • Gross CL, Meier HL, Papirmeister B, Brinkley FB, Johnson JB (1985) Sulfur mustard lowers nicotinamide adenine dinucleotide concentrations in human skin grafted to athymic nude mice. Toxicol Appl Pharmacol 81(1):85–90

    Article  PubMed  CAS  Google Scholar 

  • Gross CL, Nealley EW, Nipwoda MT, Smith WJ (2006) Pretreatment of human epidermal keratinocytes with D, L-sulforaphane protects against sulfur mustard cytotoxicity. Cutan Ocul Toxicol 25(3):155–163

    Article  PubMed  CAS  Google Scholar 

  • Guignabert C, Taysse L, Calvet JH, Planus E, Delamanche S, Galiacy S, D’ortho MP (2005) Effect of doxycycline on sulfur mustard-induced respiratory lesions in guinea pigs. Am J Physiol Lung Cell Mol Physiol 289(1):L67–L74

    Article  PubMed  CAS  Google Scholar 

  • Heinrich A, Balszuweit F, Thiermann H, Kehe K (2009) Rapid simultaneous determination of apoptosis, necrosis, and viability in sulfur mustard exposed HaCaT cell cultures. Toxicol Lett 191(2):260–267

    Article  PubMed  CAS  Google Scholar 

  • Helleday T, Petermann E, Lundin C, Hodgson B, Sharma RA (2008) DNA repair pathways as targets for cancer therapy. Nat Rev Cancer 8(3):193–204

    Article  PubMed  CAS  Google Scholar 

  • Jackson SP, Bartek J (2009) The DNA-damage response in human biology and disease. Nature 461(7267):1071–1078

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Jafari S, Saeidnia S, Abdollahi M (2014) Role of natural phenolic compounds in cancer chemoprevention via regulation of the cell cycle. Curr Pharm Biotechnol 15(4):409–421

    Article  PubMed  CAS  Google Scholar 

  • Jagtap P, Szabó C (2005) Poly(ADP-ribose) polymerase and the therapeutic effects of its inhibitors. Nat Rev Drug Discov 4(5):421–440

    Article  PubMed  CAS  Google Scholar 

  • Jenkinson P, Aderson D (1990) Malformed foetuses and karyotype abnormalities in the offspring of cyclophosphamide and allyl alcohol-treated male rats. Mutat Res Fund Mol Mech Mutagen 229(2):173–184

    Article  CAS  Google Scholar 

  • Jenkinson P, Anderson D, Gangolli S (1987) Increased incidence of abnormal foetuses in the offspring of cyclophosphamide-treated male mice. Mutat Res Genet Toxicol 188(1):57–62

    Article  CAS  Google Scholar 

  • Joseph LB, Gerecke DR, Heck DE, Black AT, Sinko PJ, Cervelli JA, Laskin JD (2011) Structural changes in the skin of hairless mice following exposure to sulfur mustard correlate with inflammation and DNA damage. Exp Mol Pathol 91(2):515–527

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Jost P, Svobodova H, Stetina R (2015) Induction and repair of DNA cross-links induced by sulfur mustard in the A-549 cell line followed by a comet assay. Chem Biol Interact 237:31–37

    Article  PubMed  CAS  Google Scholar 

  • Jowsey PA, Williams FM, Blain PG (2009) DNA damage, signalling and repair after exposure of cells to the sulphur mustard analogue 2-chloroethyl ethyl sulphide. Toxicology 257(3):105–112

    Article  PubMed  CAS  Google Scholar 

  • Jowsey PA, Williams FM, Blain PG (2012) DNA damage responses in cells exposed to sulphur mustard. Toxicol Lett 209(1):1–10

    Article  PubMed  CAS  Google Scholar 

  • Karalliedde L, Wheeler H, Maclehose R, Murray V (2000) Possible immediate and long-term health effects following exposure to chemical warfare agents. Public Health 114(4):238–248

    Article  PubMed  CAS  Google Scholar 

  • Kastan MB, Bartek J (2004) Cell-cycle checkpoints and cancer. Nature 432(7015):316–323

    Article  PubMed  CAS  Google Scholar 

  • Kehe K, Szinicz L (2005) Medical aspects of sulphur mustard poisoning. Toxicology 214(3):198–209

    Article  PubMed  CAS  Google Scholar 

  • Ketabchi A (1998) Urogenital and fertility complications in victims of chemical war residing in Kerman province. J Kerman Univ Med Sci 5(2):72–77

    Google Scholar 

  • Khaheshi I, Keshavarz S, Fooladi AAI, Ebrahimi M, Yazdani S, Panahi Y, Nourani MR (2011) Loss of expression of TGF-βs and their receptors in chronic skin lesions induced by sulfur mustard as compared with chronic contact dermatitis patients. BMC Dermatol 11(1):1. doi:10.1186/1471-5945-11-2

    Article  CAS  Google Scholar 

  • Khan F, Niaz K, Maqbool F, Ismail Hassan F, Abdollahi M, Nagulapalli Venkata KC, Bishayee A (2016) Molecular targets underlying the anticancer effects of quercetin: an update. Nutrients 8(9):529–548. doi:10.3390/nu8090529

    Article  PubMed Central  CAS  Google Scholar 

  • Kooshesh L, Dashtnavard H, Bahadoran H, Karimi A, Jafari M, Asadi M (2007) Evaluation of sulfur mustard effect on the spermatogenesis process of mature male rats. J Iran Anat Sci 5:27–36

    Google Scholar 

  • Korkmaz A, Tan DX, Reiter R (2008) Acute and delayed sulfur mustard toxicity; novel mechanisms and future studies. Interdiscip Toxicol 1(1):22–26

    Article  PubMed  PubMed Central  Google Scholar 

  • Kumar D, Tewari-Singh N, Agarwal C, Jain AK, Inturi S, Kant R et al (2015) Nitrogen mustard exposure of murine skin induces DNA damage, oxidative stress and activation of MAPK/Akt-AP1 pathway leading to induction of inflammatory and proteolytic mediators. Toxicol Lett 235(3):161–171

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lavranos G, Balla M, Tzortzopoulou A, Syriou V, Angelopoulou R (2012) Investigating ROS sources in male infertility: a common end for numerous pathways. Reprod Toxicol 34(3):298–307

    Article  PubMed  CAS  Google Scholar 

  • Lodhi IJ, Sweeney JF, Clift RE, Hinshaw DB (2001) Nuclear dependence of sulfur mustard-mediated cell death. Toxicol Appl Pharmacol 170(1):69–77

    Article  PubMed  CAS  Google Scholar 

  • Lu J, Huang Y, Lü N (2010) WHO laboratory manual for the examination and processing of human semen: its applicability to andrology laboratories in China. Zhonghua nan ke xue = Natl J Androl 16(10):867–871

    Google Scholar 

  • Ludlum DB, Papirmeister B (1986) DNA modification by sulfur mustards and nitrosoureas and repair of these lesions mechanisms of DNA damage and repair. Springer, New York, pp 119–125

    Google Scholar 

  • Ludlum DB, Austin-Ritchie P, Hagopian M, Niu TQ, Yu D (1994) Detection of sulfur mustard-induced DNA modifications. Chem Biol Interact 91(1):39–49

    Article  PubMed  CAS  Google Scholar 

  • Mansour Razavi S, Salamati P, Saghafinia M, Abdollahi M (2012) A review on delayed toxic effects of sulfur mustard in Iranian veterans. DARU 20(1):51–59. doi:10.1186/2008-2231-20-51

    Article  PubMed  PubMed Central  Google Scholar 

  • Matsuo K, Kooshesh S, Dinc M, Sun CCJ, Kimura T, Baschat AA (2007) Late postpartum eclampsia: report of two cases managed by uterine curettage and review of the literature. Am J Perinatol 24(04):257–266

    Article  PubMed  Google Scholar 

  • Munro NB, Talmage SS, Griffin GD, Waters LC, Watson AP, King JF, Hauschild V (1999) The sources, fate, and toxicity of chemical warfare agent degradation products. Environ Health Perspect 107(12):933–974

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Nair PC, McKinnon RA, Miners JO (2016) Cytochrome P450 structure–function: insights from molecular dynamics simulations. Drug Metab Rev 48(3):1–19

    Article  Google Scholar 

  • Najafi A, Masoudi-Nejad A, Imani Fooladi AA, Ghanei M, Nourani MR (2014) Microarray gene expression analysis of the human airway in patients exposed to sulfur mustard. J Recept Signal Transduct 34(4):283–289

    Article  CAS  Google Scholar 

  • Nicotera P, Bellomo G, Orrenius S (1992) Calcium-mediated mechanisms in chemically induced cell death. Ann Rev Pharmacol Toxicol 32(1):449–470

    Article  CAS  Google Scholar 

  • Nourani MR, Mahmoodzadeh Hosseini H, Azimzadeh Jamalkandi S, Imani Fooladi AA (2016) Cellular and molecular mechanisms of acute exposure to sulfur mustard: a systematic review. J Recept Signal Transduct. doi:10.1080/10799893.2016.1212374

    Article  Google Scholar 

  • Panahi Y, Davoudi SM, Sadr SB, Naghizadeh MM, Mohammadi-Mofrad M (2008) Impact of pruritus on quality of life in sulfur mustard-exposed Iranian veterans. Int J Dermatol 47(6):557–561

    Article  PubMed  Google Scholar 

  • Panahi Y, Moharamzad Y, Beiraghdar F, Naghizadeh MM (2009) Comparison of clinical efficacy of topical pimecrolimus with betamethasone in chronic skin lesions due to sulfur mustard exposure: a randomized, investigator-blind study. Basic Clin Pharmacol Toxicol 104(2):171–175

    Article  PubMed  CAS  Google Scholar 

  • Panahi Y, Ghanei M, Ghabili K, Ansarin K, Aslanabadi S, Poursaleh Z et al (2013) Acute and chronic pathological effects of sulfur mustard on genitourinary system and male fertility. Urol J 10(2):837–846

    PubMed  Google Scholar 

  • Pant SC, Lomash V (2016) Sulphur mustard induced toxicity, mechanism of action and current medical management. Def Life Sci J 1(1):7–17. doi:10.14429/dlsj.1.10089

    Article  Google Scholar 

  • Papirmeister B, Gross CL, Meier HL, Petrali JP, Johnson JB (1985) Molecular basis for mustard-induced vesication. Fund Appl Toxicol 5(6):S134–S149

    Article  CAS  Google Scholar 

  • Paromov V, Kumari S, Brannon M, Kanaparthy NS, Yang H, Smith MG, Stone WL (2011) Protective effect of liposome-encapsulated glutathione in a human epidermal model exposed to a mustard gas analog. J Toxicol 2011(2011):1–11. doi:10.1155/2011/109516

    Article  CAS  Google Scholar 

  • Pohanka M, Sobotka J, Svobodova H, Stetina R (2013) Sulfur mustard induced oxidative stress and its alteration using asoxime (HI-6). Interdiscip Toxicol 6(4):198–202

    Article  PubMed  PubMed Central  Google Scholar 

  • Pounds JG (1990) The role of cell calcium in current approaches to toxicology. Environ Health Persp 84:7–15

    Article  CAS  Google Scholar 

  • Pour-Jafari H (1994) Congenital malformations in the progenies of Iranian chemical victims. Vet Hum Toxicol 36(6):562–3

    PubMed  CAS  Google Scholar 

  • Pour-Jafari H, Moushtaghi A (1992) Alterations of libido in gased Iranian men. Vet Hum Toxicol 34(6):547

    PubMed  CAS  Google Scholar 

  • Poursaleh Z, Harandi AA, Vahedi E, Ghanei M (2012) Treatment for sulfur mustard lung injuries; new therapeutic approaches from acute to chronic phase. DARU 20(1):27–38. doi:10.1186/2008-2231-20-27

    Article  PubMed  PubMed Central  Google Scholar 

  • Rao S, Matsumura A, Yoon J, Simon MC (1999) SPI-B activates transcription via a unique proline, serine, and threonine domain and exhibits DNA binding affinity differences from PU. 1. J Biol Chem 274(16):11115–11124

    Article  PubMed  CAS  Google Scholar 

  • Ray R, Legere R, Majerus B, Petrali J (1995) Sulfur mustard-induced increase in intracellular free calcium level and arachidonic acid release from cell membrane. Toxicol Appl Pharmacol 131(1):44–52

    Article  PubMed  CAS  Google Scholar 

  • Razavi SM, Ghanei M, Salamati P, Safiabadi M (2013) Long-term effects of mustard gas on respiratory system of Iranian veterans after Iraq–Iran war: a review. Chin J Traumatol 16(3):163–168

    PubMed  Google Scholar 

  • Razavi SM, Abdollahi M, Salamati P (2016) Cancer events after acute or chronic exposure to sulfur mustard: a review of the literature. Int J Prev Med 7:79. doi:10.4103/2008-7802.182733

    Article  Google Scholar 

  • Rezvanfar M, Sadrkhanlou R, Ahmadi A, Shojaei-Sadee H, Mohammadirad A, Salehnia A, Abdollahi M (2008) Protection of cyclophosphamide-induced toxicity in reproductive tract histology, sperm characteristics, and DNA damage by an herbal source; evidence for role of free-radical toxic stress. Hum Exp Toxicol 27(12):901–910

    Article  PubMed  CAS  Google Scholar 

  • Rosenthal DS, Simbulan-Rosenthal CM, Liu WF, Velena A, Anderson D, Benton B et al (2001) PARP determines the mode of cell death in skin fibroblasts, but not keratinocytes, exposed to sulfur mustard. J Invest Dermatol 117(6):1566–1573

    Article  PubMed  CAS  Google Scholar 

  • Ruff AL, Dillman JF (2010) Sulfur mustard induced cytokine production and cell death: investigating the potential roles of the p38, p53, and NF-κB signaling pathways with RNA interference. J Biochem Mol Toxicol 24(3):155–164

    Article  PubMed  CAS  Google Scholar 

  • Saeidnia S, Abdollahi M (2013) Antioxidants: friends or foe in prevention or treatment of cancer: the debate of the century. Toxicol Appl Pharmacol 271(1):49–63

    Article  PubMed  CAS  Google Scholar 

  • Safarinejad M (2001) Testicular effect of mustard gas. Urology 58(1):90–94

    Article  PubMed  CAS  Google Scholar 

  • Safarinejad MR (2010) Sperm chromatin structure assay analysis of Iranian mustard gas casualties: a long-term outlook. Curr Urol 4(2):71–80

    Article  CAS  Google Scholar 

  • Safarinejad MR, Kolahi AA, Iravani S (2010) Evaluation of semen variables, sperm chromosomal abnormalities and reproductive endocrine profile in patients with chronic hepatitis C. BJU Int 105(1):79–86

    Article  PubMed  CAS  Google Scholar 

  • Sasser L, Cushing J, Dacre J (1993) Dominant lethal study of sulfur mustard in male and female rats. J Appl Toxicol 13(5):359–368

    Article  PubMed  CAS  Google Scholar 

  • Sauvaigo S, Sarrazy F, Batal M, Caillat S, Pitiot B, Mouret S et al (2016) Impact of topical application of sulfur mustard on mice skin and distant organs DNA repair enzyme signature. Toxicol Lett 241:71–81

    Article  PubMed  CAS  Google Scholar 

  • Sayed HM, Fouad D, Ataya FS, Hassan NH, Fahmy MA (2012) The modifying effect of selenium and vitamins A, C, and E on the genotoxicity induced by sunset yellow in male mice. Mutat Res Genet Toxicol Environ Mut 744(2):145–153

    Article  CAS  Google Scholar 

  • Shakeri S, Yazdani M, Kheradpezhouh E (2007) Long-term effect of exposure to mustard gas on male infertility. Iran Red Crescent Med J 2:59–62

    Google Scholar 

  • Simbulan-Rosenthal CM, Ray R, Benton B, Soeda E, Daher A, Anderson D et al (2006) Calmodulin mediates sulfur mustard toxicity in human keratinocytes. Toxicology 227(1):21–35

    Article  PubMed  CAS  Google Scholar 

  • Soroush M, Modirian E, Sh K (2008) Long-term effects of exposure to mustard gas on male infertility. Iran Red Crescent Med J 4:344–345

    Google Scholar 

  • Spratlin JL, Serkova NJ, Eckhardt SG (2009) Clinical applications of metabolomics in oncology: a review. Clin Cancer Res 15(2):431–440

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Szabo C, Zingarelli B, O’Connor M, Salzman AL (1996) DNA strand breakage, activation of poly(ADP-ribose) synthetase, and cellular energy depletion are involved in the cytotoxicity of macrophages and smooth muscle cells exposed to peroxynitrite. Proc Natl Acad Sci 93(5):1753–1758

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Taher AA (1992) Cleft lip and palate in Tehran. Cleft Palate Craniofac J 29(1):15–16

    Article  PubMed  CAS  Google Scholar 

  • Tahmasbpour E, Balasubramanian D, Agarwal A (2014) A multi-faceted approach to understanding male infertility: gene mutations, molecular defects and assisted reproductive techniques (ART). J Assist Reprod Genet 31(9):1115–1137

    Article  PubMed  PubMed Central  Google Scholar 

  • Uzych L (1985) Teratogenesis and mutagenesis associated with the exposure of human males to lead: a review. Yale J Biol Med 58(1):9–17

    PubMed  PubMed Central  CAS  Google Scholar 

  • Watson A, Opresko D, Young R, Hauschild V (2006) Development and application of acute exposure guideline levels (AEGLs) for chemical warfare nerve and sulfur mustard agents. J Toxicol Environ Health Crit Rev 9(3):173–263

    Article  CAS  Google Scholar 

  • Zafarghandi MR, Soroush MR, Mahmoodi M, Naieni KH, Ardalan A, Dolatyari A et al (2013) Incidence of cancer in Iranian sulfur mustard exposed veterans: a long-term follow-up cohort study. Cancer Causes Control 24(1):99–105

    Article  PubMed  Google Scholar 

  • Zamani Z, Ghanei M, Panahi Y, Arjmand M, Sadeghi S, Mirkhani F et al (2016) Serum metabolomic profiling of sulphur mustard-exposed individuals using 1HNuclear magnetic resonance spectroscopy. Basic Clin Pharmacol Toxicol 118(1):77–82

    Article  PubMed  CAS  Google Scholar 

  • Zhang Z, Peters B, Monteiro-Riviere N (1995) Assessment of sulfur mustard interaction with basement membrane components. Cell Biol Toxicol 11(2):89–101

    Article  PubMed  CAS  Google Scholar 

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  1. International Campus, Tehran University of Medical Sciences (IC-TUMS), Tehran, Iran

    Fazlullah Khan, Kamal Niaz, Fatima Ismail Hassan & Mohammad Abdollahi

  2. Toxicology and Diseases Group, Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran

    Fazlullah Khan, Kamal Niaz, Fatima Ismail Hassan & Mohammad Abdollahi

  3. Department of Toxicology and Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, 1417614411, Iran

    Fazlullah Khan, Kamal Niaz, Fatima Ismail Hassan & Mohammad Abdollahi

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Khan, F., Niaz, K., Ismail Hassan, F. et al. An evidence-based review of the genotoxic and reproductive effects of sulfur mustard. Arch Toxicol 91, 1143–1156 (2017). https://doi.org/10.1007/s00204-016-1911-8

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