Genotoxicity of inhalational anesthetics and its relationship with the polymorphisms of GSTT1, GSTM1, and GSTP1 genes
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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.
KeywordsOperating room Micronucleus Chromosomal aberrations GST genes polymorphisms
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.
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.
- 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
- 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
- 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
- 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
- Fenech M, Morley A (1985) Solutions to the kinetic problem in the micronucleus assay. Cytobios 43:233–246Google Scholar
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- NIOSH (1994) National Institute of occupational safety and health. Anal Methods 6600Google Scholar
- 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
- OSHA (2010) Enflurane halothane isoflurane (Organic Method #103)Google Scholar
- 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
- Rozgaj R, Kasuba V (2001) Chromosome aberrations and micronucleus frequency in anaesthesiology personnel. Arhiv za higijenu rada i toksikologiju 51:361–368Google Scholar
- 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
- 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
- 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