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Genotoxicity of inhalational anesthetics and its relationship with the polymorphisms of GSTT1, GSTM1, and GSTP1 genes

  • Fatemeh Kargar Shouroki
  • Masoud Neghab
  • Hossein Mozdarani
  • Hamzeh Alipour
  • Saeed Yousefinejad
  • Reza Fardid
Research Article
  • 49 Downloads

Abstract

Due to their wide applications, concern exists regarding possible genotoxic effects of inhalational anesthetics (IAs) among operating room personnel. This study was undertaken to examine genotoxic properties of co-exposure to nitrous oxide, sevoflurane, and isoflurane on induction of micronucleus (MN) and chromosomal aberrations (CAs) and to determine whether any associations exist between polymorphisms of GST genes and the level of genomic damage measured by MN and CAs assays. Sixty operating room personnel and 60 unexposed referent nurses were studied. The workers’ exposure to the IAs was determined. DNA damage was evaluated by MN and CAs assays. Additionally, the GSTM1, GSTT1, and GSTP1 polymorphisms were detected. The mean concentrations of nitrous oxide, isoflurane, and sevoflurane were found to be 850.92 ± 919.78, 2.40 ± 0.86, and 0.18 ± 0.14 ppm, respectively. The frequency of MN and CAs in the exposed group was significantly higher than that of the non-exposed group. The frequency of MN was significantly higher in referent nurses with null GSTT1, compared to referent nurses with positive GSTT1. The frequency of MN was significantly higher in exposed individuals carrying the combined genotype of GSTT1 (−), GSTM1 (−), and GSTP1 AG as compared with subjects carrying a combination of GSTT1 (+), GSTM1 (+), and GSTP1 AA. Statistically significant associations were noted between exposure to the IAs, gender, and the combination of the three GSTs genotypes with MN frequency. These findings indicate that inhalation exposure to IAs induces genotoxic response and the polymorphisms of GSTs genes might modulate the effect of exposure to IAs on MN.

Keywords

Operating room Micronucleus Chromosomal aberrations GST genes polymorphisms 

Notes

Acknowledgements

The materials embodied in this manuscript have been emanated from the PhD thesis of Mrs. Kargar Shouroki, the first author of this paper, supervised by Professor Neghab and Professor Mozdarani.

Funding information

This work was supported by the Shiraz University of Medical Science (SUMS) under Grant (95-01-04-12366).

Compliance with ethical standards

The study was conducted in accordance with the Helsinki Declaration of 1964 as revised in 2013 (WMA 2013).

Conflict of interest

The authors declare that there is no conflict of interest.

References

  1. Aldrieny EAE, Abd-el-hafez AA (2013) Effects of wasted anesthetic gases on human lymphocytes—a genetic study. J Microscopy Ultrastruct 1:89–95CrossRefGoogle Scholar
  2. Battershill J, Burnett K, Bull S (2008) Factors affecting the incidence of genotoxicity biomarkers in peripheral blood lymphocytes: impact on design of biomonitoring studies. Mutagenesis 23:423–437CrossRefGoogle Scholar
  3. Bezerra FJ, Vale NBD, Macedo BDO, Rezende AA, Almeida MDG (2010) Evaluation of antioxidant parameters in eats treated with sevoflurane. Rev Bras Anestesiol 60:162–165CrossRefGoogle Scholar
  4. Bilban M, Jakopin CB, Ogrinc D (2005) Cytogenetic tests performed on operating room personnel (the use of anaesthetic gases). Int Arch Occup Environ Health 78:60–64CrossRefGoogle Scholar
  5. Bonassi S, Coskun E, Ceppi M, Lando C, Bolognesi C, Burgaz S, Holland N, Kirsh-volder M, Knasmueller S, Zeiger E (2011) The HUman MicroNucleus project on eXfoLiated buccal cells (HUMN XL): the role of life-style, host factors, occupational exposures, health status, and assay protocol. Mutat Res Rev Mutat Res 728:88–97CrossRefGoogle Scholar
  6. Çakmak G, Eraydin D, Berkkan A, Yagar S, Burgaz S (2018) Genetic damage of operating and recovery room personnel occupationally exposed to waste anaesthetic gases. Hum Exp Toxicol:1–8Google Scholar
  7. Casale T, Caciari T, Rosati MV, Gioffrè PA, Schifano MP, Capozzella A (2014) Anesthetic gases and occupationally exposed workers. Environ Toxicol Pharmacol 37:267–274CrossRefGoogle Scholar
  8. Chandrasekhar M, Rekhadevi P, Sailaja N, Rahman M, Reddy J, Mahboob M, Grover P (2006) Evaluation of genetic damage in operating room personnel exposed to anaesthetic gases. Mutagenesis 21:249–254CrossRefGoogle Scholar
  9. Chang WP, Lee SR, Tu J, Hseu SS (1996) Increased micronucleus formation in nurses with occupational nitrous oxide exposure in operating theaters. Environ Mol Mutagen 27:93–97CrossRefGoogle Scholar
  10. Chang TW, Wang SM, Guo YL, Tsai PC, Huang CJ, Huang W (2006) Glutathione S-transferase polymorphisms associated with risk of breast cancer in southern Taiwan. Breast 15:754–761CrossRefGoogle Scholar
  11. Cheng X, Zhang T, Zhao J, Zhou J, Shao H, Zhou Z, Kong F, Feng N, Sun Y, Shan B (2013) The association between genetic damage in peripheral blood lymphocytes and polymorphisms of three glutathione S-transferases in Chinese workers exposed to 1,3-butadiene. Mutat Res Genet Toxicol Environ Mutagen 750:139–146CrossRefGoogle Scholar
  12. Datta SK, Kumar V, Pathak R, Tripathi AK, Ahmed RS, Kalra OP, Banerjee BD (2010) Association of glutathione S-transferase M1 and T1 gene polymorphism with oxidative stress in diabetic and nondiabetic chronic kidney disease. Ren Fail 32:1189–1195CrossRefGoogle Scholar
  13. De Araujo TK, da Silva-Grecco RL, Bisinotto FMB, Roso NC, Pissetti CW, da Cruz RM, Balarin MAS (2013) Genotoxic effects of anesthetics in operating room personnel evaluated by micronucleus test. J Anesthesiol Clin Res 2:26–31Google Scholar
  14. Deng HB, Li FX, Cai YH, Xu SY (2018) Waste anesthetic gas exposure and strategies for solution. J Anesth 32:269–282CrossRefGoogle Scholar
  15. EL-ebiary A, Abuelfadl A, Sarhan N, Othman M (2013) Assessment of genotoxicity risk in operation room personnel by the alkaline comet assay. Hum Exp Toxicol 32:563–570CrossRefGoogle Scholar
  16. Fenech M (2006) Cytokinesis-block micronucleus assay evolves into a “cytome” assay of chromosomal instability, mitotic dysfunction and cell death. Mutat Res Fundam Mol Mech Mutagen 600:58–66CrossRefGoogle Scholar
  17. Fenech M, Bonassi S (2011) The effect of age, gender, diet and lifestyle on DNA damage measured using micronucleus frequency in human peripheral blood lymphocytes. Mutagenesis 26:43–49CrossRefGoogle Scholar
  18. Fenech M, Morley A (1985) Solutions to the kinetic problem in the micronucleus assay. Cytobios 43:233–246Google Scholar
  19. Ge B, Sa AEM, Ss EG, Am EN, Ma H (2018) Occupational genotoxic effects among a group of nurses exposed to anesthetic gases in operating rooms at Zagazig University Hospitals. Egypt J Occup Med 42:105–122CrossRefGoogle Scholar
  20. Handayani R, Abdullah T, Naeim F, Mallongi A, Saeni RH, Ahmad EH, Prihantono P (2018) Effects of isoflurane exposure to fertility through estrogen gene expression in operating room nurses. Am J Public Health 6:11–17Google Scholar
  21. Heuser VD, Erdtmann B, Kvitko K, Rohr P, Da Silva J (2007) Evaluation of genetic damage in Brazilian footwear-workers: biomarkers of exposure, effect, and susceptibility. Toxicology 232:235–247CrossRefGoogle Scholar
  22. Hobbhahn J, Wiesner G, Taeger K (1998) Occupational exposure and environmental pollution: the role of inhalation anesthetics with special consideration of sevoflurane. Anaesthesist 47:77–86CrossRefGoogle Scholar
  23. Hoerauf K, Lierz M, Wiesner G, Schroegendorfer K, Lierz P, Spacek A, Brunnberg L, Nusse M (1999) Genetic damage in operating room personnel exposed to isoflurane and nitrous oxide. Occup Environ Med 56:433–437CrossRefGoogle Scholar
  24. Iarmarcovai G, Bonassi S, Botta A, Baan R, Orsiere T (2008) Genetic polymorphisms and micronucleus formation: a review of the literature. Mutat Res Rev Mutat Res 658:215–233CrossRefGoogle Scholar
  25. Jafari A, Bargeshadi R, Jafari F, Mohebbi I, Hajaghazadeh M (2018) Environmental and biological measurements of isoflurane and sevoflurane in operating room personnel. Int Arch Occup Environ Health 91:349–359CrossRefGoogle Scholar
  26. Kaymak C, Karahalil, Ozcan N, Oztuna D (2008) Association between GSTP1 gene polymorphism and serum α-GST concentrations undergoing sevoflurane anaesthesia. Eur J Anaesthesiol 25:193–199CrossRefGoogle Scholar
  27. Kirsch-Volders M, Mateuca RA, Roelants M, Tremp A, Zeiger E, Bonassi S, Holland N, Chang WP, AKA PV, Deboeck M (2006) The effects of GSTM1 and GSTT1 polymorphisms on micronucleus frequencies in human lymphocytes in vivo. Cancer Epidemiol Prev Biomarkers 15:1038–1042CrossRefGoogle Scholar
  28. Krajewski W, Kucharska M, Pilacik B, Fobker M, Stetkiewicz Tetkiewicz J, Nofer JR, Wronska-Nofer T (2007) Impaired vitamin B12 metabolic status in healthcare workers occupationally exposed to nitrous oxide. Br J Anaesth 99:812–818CrossRefGoogle Scholar
  29. Laffon B, Teixeira JP, Silva S, Roma-Torres J, Perez-Cadahia B, Méndez J, Pasaro E, Mayan O (2006) Assessment of occupational genotoxic risk in the production of rubber tyres. Ann Occup Hyg 50:583–592Google Scholar
  30. Lewinska D, Stępnik M, Krajewski W, Arkusz J, Stańczyk M, Wrońska-Nofer T (2005) Increased incidence of micronuclei assessed with the micronucleus assay and the fluorescence in situ hybridization (FISH) technique in peripheral blood lymphocytes of nurses exposed to nitrous oxide. Mutat Res Genet Toxicol Environ Mutagen 581:1–9CrossRefGoogle Scholar
  31. Lin CY, Wu JL, Shih TS, Tsai PJ, Sun YM, Guo YL (2009) Glutathione S-transferase M1, T1, and P1 polymorphisms as susceptibility factors for noise-induced temporary threshold shift. Hear Res 257:8–15CrossRefGoogle Scholar
  32. Lucchini R, Placidi D, Toffoletto F, Alessio L (1996) Neurotoxicity in operating room personnel working with gaseous and nongaseous anesthesia. Int Arch Occup Environ Health 68:188–192CrossRefGoogle Scholar
  33. Lucio L, Braz MG, Nascimento junior PD, Braz JRC, Braz LG (2018) Occupational hazards, DNA damage, and oxidative stress on exposure to waste anesthetic gases. Rev Bras Anestesiol 68:33–41CrossRefGoogle Scholar
  34. Migliore L, Naccarati A, Coppede F, Bergamaschi E, De Palma G, Voho A et al (2006) Cytogenetic biomarkers, urinary metabolites and metabolic gene polymorphisms in workers exposed to styrene. Pharmacogenet Genomics 16:87–99CrossRefGoogle Scholar
  35. Mikstack A, Skrzypczak-zielinska M, Zakerska-Banaszak O, Tamowicz B, Skibinska M, Molinska-glura M, Szalata M, Slomski R (2016) Impact of CYP2E1, GSTA1 and GSTP1 gene variants on serum alpha glutathione S-transferase level in patients undergoing anaesthesia. BMC Med Genet 17:40–47CrossRefGoogle Scholar
  36. Montero R, Serrano L, Araujo A, Dávila V, Ponce J, Camacho R, Morales E, Mendez A (2006) Increased cytogenetic damage in a zone in transition from agricultural to industrial use: comprehensive analysis of the micronucleus test in peripheral blood lymphocytes. Mutagenesis 21:335–342CrossRefGoogle Scholar
  37. Musak Ľ, Halasova E, Matakova T, Letkova L, Vodickova L, Buchancova J et al (2009) Comparison of chromosomal aberrations frequency and polymorphism of GSTs genes in workers occupationally exposed to cytostatics or anaesthetics. Interdiscip Toxicol 2:190–194Google Scholar
  38. Musak L, Smerhovsky Z, Halasova E, Osina O, Letkova L, Vodickova OL, Polakova V, Buchancova J, Hemminki K, Vodicka P (2013) Chromosomal damage among medical staff occupationally exposed to volatile anesthetics, antineoplastic drugs, and formaldehyde. Scand J Work Environ Health 39:618–630CrossRefGoogle Scholar
  39. Nagella AB, Ravishankar M, Kumar VH (2015) Anaesthesia practice and reproductive outcomes: facts unveiled. Indian J Anaesthesia 59:706–714CrossRefGoogle Scholar
  40. Neghab M, Nourozi MA, Shahtaheri SJ, Mansoori Y, Bazzaz JT, Nedjat S (2018) Effects of genetic polymorphism on susceptibility to nephrotoxic properties of BTEXs compounds. J Occup Environ Med 60:337–382CrossRefGoogle Scholar
  41. NIOSH (1994) National Institute of occupational safety and health. Anal Methods 6600Google Scholar
  42. NIOSH: National Institute of Occupational Safety and Health (1977) Criteria for a recommended standard: occupational exposure to waste anesthetic gases and vapors, Cincinnati, Ohio, USA: United States Department of Health, Education, and Welfare (DHEW): 77–140Google Scholar
  43. Norizadeh Tazekand M, Topaktas M (2015) The in vitro genotoxic and cytotoxic effects of remeron on human peripheral blood lymphocytes. Drug Chem Toxicol 38:266–271CrossRefGoogle Scholar
  44. Norppa H, Falck GCM (2003) What do human micronuclei contain? Mutagenesis 18:221–233CrossRefGoogle Scholar
  45. Nourozi MA, Neghab M, Bazzaz JT, Nejat S, Mansoori Y, Shahtaheri SJ (2018) Association between polymorphism of GSTP1, GSTT1, GSTM1 and CYP2E1 genes and susceptibility to benzene-induced hematotoxicity. Arch Toxicol 92:1983–1990CrossRefGoogle Scholar
  46. OSHA (2010) Enflurane halothane isoflurane (Organic Method #103)Google Scholar
  47. Otedo A (2004) Halothane induced hepatitis: case report. East Afr Med J 81:538–539CrossRefGoogle Scholar
  48. Paes ERDC, Braz MG, Lima JTD, SilvaI MRGD, Sousa LBD, Lima ES, Vasconcellos MCD, Braz JRC (2014) DNA damage and antioxidant status in medical residents occupationally exposed to waste anesthetic gases. Acta Cir Bras 29:280–286CrossRefGoogle Scholar
  49. Pasquini R, Scassellati-Sforzolini G, Fatigoni C, Marcarelli M, Monarca S, Donato F, Cencetti S, Cerami FM (2001) Sister chromatid exchanges and micronuclei in lymphocytes of operating room personnel occupationally exposed to enfluorane and nitrous oxide. J Environ Pathol Toxicol Oncol 20:119–126CrossRefGoogle Scholar
  50. Restreepo JG, Garicaa-Martin E, Martinez C, Agundez JA (2009) Polymorphic drug metabolism in anaesthesia. Curr Drug Metab 10:236–246CrossRefGoogle Scholar
  51. Rozgaj R, Kasuba V (2001) Chromosome aberrations and micronucleus frequency in anaesthesiology personnel. Arhiv za higijenu rada i toksikologiju 51:361–368Google Scholar
  52. Rozgaj R, Kasuba V, Jazbec A (2001) Preliminary study of cytogenetic damage in personnel exposed to anesthetic gases. Mutagenesis 16:139–143CrossRefGoogle Scholar
  53. Rozgaj R, Kašuba V, Brozović G, Jazbec A (2009) Genotoxic effects of anaesthetics in operating theatre personnel evaluated by the comet assay and micronucleus test. Int J Hyg Environ Health 212:11–17CrossRefGoogle Scholar
  54. Sakhvidi MJZ, Bahrami A, Ghiasvand A, Mahjub H, Tuduri L (2012) Field application of SPME as a novel tool for occupational exposure assessment with inhalational anesthetics. Environ Monit Assess 184:6483–6490CrossRefGoogle Scholar
  55. Santovito A, Cervella P, Delpero M (2014) Increased frequency of chromosomal aberrations and sister chromatid exchanges in peripheral lymphocytes of radiology technicians chronically exposed to low levels of ionizing radiations. Environ Toxicol Pharmacol 37:396–403CrossRefGoogle Scholar
  56. Santovito A, Cervella P, Delpero M (2015) Evaluation of genomic damage in peripheral lymphocytes from occupationally exposed anesthetists: assessment of the effects of age, sex, and GSTT1 gene polymorphism. J Biochem Mol Toxicol 29:234–239CrossRefGoogle Scholar
  57. Scapellato ML, Mastrangelo G, Fedeli U, Carrieri M, Macca L, Scoizzato L, Bartolucci GB (2008) A longitudinal study for investigating the exposure level of anesthetics that impairs neurobehavioral performance. Neurotoxicology 29:116–123CrossRefGoogle Scholar
  58. Schifilliti D, Mondello S, D’arrigoA MG, Chille G, Fodale V (2011) Genotoxic effects of anesthetic agents: an update. Expert Opin Drug Saf 10:891–899CrossRefGoogle Scholar
  59. Shaker DA, Samir AM, Hagag HA, EL-AAL AAA, Afify RA (2011) Cytogenetic damage in operating room nurses exposed to anesthetic gases. Med J Cairo Univ 79:237–244Google Scholar
  60. Silva MC, Gaspar J, Duarte Silva I, Faber A, Rueff J (2004) GSTM1, GSTT1, and GSTP1 genotypes and the genotoxicity of hydroquinone in human lymphocytes. Environ Mol Mutagen 43:258–264CrossRefGoogle Scholar
  61. Sindhu G, Manoharan S (2010) Anti-clastogenic effect of berberine against DMBA-induced clastogenesis. Basic Clin Pharmacol Toxicol 107:818–824CrossRefGoogle Scholar
  62. Singh M, Shah PP, Singh AP, Ruwali M, Mathur N, Pant MC, Parmar D (2008) Association of genetic polymorphisms in glutathione S-transferases and susceptibility to head and neck cancer. Mutat Res Fundam Mol Mech Mutagen 638:184–194CrossRefGoogle Scholar
  63. Singh S, Kumar V, Singh P, Thakur S, Banerjee BD, Rautela RS, Grover SS, Rawat DS, Pasha ST (2011) Genetic polymorphisms of GSTM1, GSTT1 and GSTP1 and susceptibility to DNA damage in workers occupationally exposed to organophosphate pesticides. Mutat Res Genet Toxicol Environ Mutagen 725:36–42CrossRefGoogle Scholar
  64. Souza KM, Braz LG, Nogueira FR, Souza MB, Bincoleto LF, Aun AG, Corrente JE, Carvalho LR, Braz JRC, Braz MG (2016) Occupational exposure to anesthetics leads to genomic instability, cytotoxicity and proliferative changes. Mutat Res Fundam Mol Mech Mutagen 791:42–48CrossRefGoogle Scholar
  65. Surralles J, Xamena N, Creus A, Catalan J, Norrpa H, Marcos R (1995) Induction of micronuclei by five pyrethroid insecticides in whole-blood and isolated human lymphocyte cultures. Mutat Res Genet Toxicol 341:169–184CrossRefGoogle Scholar
  66. Szyfter K, Stachecki I, Kostrzewska-Poczekaaj M, Szaumkessel M, Szyfter-Harris J, Sobczynski P (2016) Exposure to volatile anaesthetics is not followed by a massive induction of single-strand DNA breaks in operation theatre personnel. J Appl Genet 57:343–348CrossRefGoogle Scholar
  67. Tamer L, Ates NA, Ates C, Ercan B, Elipek T, Yildirim H, Çamdeviren H, Atik U, Aydin S (2005) Glutathione S-transferase M1, T1 and P1 genetic polymorphisms, cigarette smoking and gastric cancer risk. Cell Biochem Funct 23:267–272CrossRefGoogle Scholar
  68. Tanaka K, Weihrauch D, Kehl F, Ludwig LM, Ladisa JF, Kersten JR, Pagel PS, Warltier DC (2002) Mechanism of preconditioning by isoflurane in rabbits: a direct role for reactive oxygen species. Anesthesiology 97:1485–1490CrossRefGoogle Scholar
  69. Teschke K, Abanto Z, Arbour L, Beking K, Chow Y, Gallagher RP, Jong B, LE ND, Ratner PA, Spinelli JJ (2011) Exposure to anesthetic gases and congenital anomalies in offspring of female registered nurses. Am J Ind Med 54:118–127CrossRefGoogle Scholar
  70. Wiesner G, Hoerauf K, Schroegendorfer K, Sobczynski P, Harth M, Ruediger HW (2001) High-level, but not low-level, occupational exposure to inhaled anesthetics is associated with genotoxicity in the micronucleus assay. Anesth Analg 9:118–122CrossRefGoogle Scholar
  71. Wiesner G, Schiewe-Langgartner F, Lindner R, Gruber M (2008) Increased formation of sister chromatid exchanges, but not of micronuclei, in anaesthetists exposed to low levels of sevoflurane. Anaesthesia 63:861–864CrossRefGoogle Scholar
  72. World Health Organization [WHO] (1987) IARC monographs on the evaluation of carcinogenic risks to humans overall evaluations of carcinogenicity: an updating of IARC monographs volumes 1 to 42. International Agency for Research on Cancer. Anaesthetics Volatile 7:20–22Google Scholar
  73. World Medical Association [WMA] (2013) Declaration of Helsinki: ethical principles for medical research involving human subjects. Jama 310:2191–2194CrossRefGoogle Scholar
  74. Wrońska-Nofer T, Nofer J-R, Jajte J, Dziubałtowska E, Szymczak W, Krajewski W, Wąsowicz W, Rydzyński K (2012) Oxidative DNA damage and oxidative stress in subjects occupationally exposed to nitrous oxide (N2O). Mutat Res Fundam Mol Mech Mutagen 731:58–63CrossRefGoogle Scholar
  75. Yilmaz S, Çalbayram NÇ (2016) Exposure to anesthetic gases among operating room personnel and risk of genotoxicity: a systematic review of the human biomonitoring studies. J Clin Anesth 35:326–331CrossRefGoogle Scholar
  76. Yuille M, Condie A, Hudson C, Kote-Jarai Z, Stone E, Eeles R, Matutes E, Catovsky D, Houlston R (2002) Relationship between glutathione S-transferase M1, T1, and P1 polymorphisms and chronic lymphocytic leukemia. Blood 99:4216–4218CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Fatemeh Kargar Shouroki
    • 1
  • Masoud Neghab
    • 2
  • Hossein Mozdarani
    • 3
  • Hamzeh Alipour
    • 4
  • Saeed Yousefinejad
    • 5
  • Reza Fardid
    • 6
  1. 1.Student Research CommitteeShiraz University of Medical SciencesShirazIran
  2. 2.Department of Occupational Health Engineering, Research Center for Health Sciences, Institute of Health, School of HealthShiraz University of Medical SciencesShirazIran
  3. 3.Department of Medical Genetics, Faculty of Medical SciencesTarbiat Modares UniversityTehranIran
  4. 4.Research Center for Health Sciences, Institute of healthShiraz University of Medical SciencesShirazIran
  5. 5.Department of Occupational Health Engineering, School of HealthShiraz University of Medical SciencesShirazIran
  6. 6.Department of Radiology, School of Paramedical SciencesShiraz University of Medical SciencesShirazIran

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