•  
  •  
 

Abstract

Background: This study aimed to identify suitable biomarkers of formaldehyde exposure to conduct health surveillance among embalmers. Micronucleus frequency, DNA damage, and genetic polymorphisms were studied.

Methods: Ninety-eight staff in 13 hospitals were recruited and categorized into high or low formaldehyde exposure groups (n=49 for each group). For each participant, personal air sampling was taken and analyzed using the NIOSH method 2016. On the same day of air sampling, participants’ buccal tissue was collected and analyzed for micronucleus frequency by staining, DNA damage using the Comet assay, and polymorphism of Glutathione S-Transferase Pi 1 (GSTP1) by polymerase chain reaction methods. The average formaldehyde exposure concentration of the high-exposure group was 0.211 ± 0.482 ppm, which was higher than that of the low-exposure group (0.016 ± 0.017 ppm.) (P < 0.05).

Results: For DNA damage, the average of tail length and %tail DNA, of the high exposure group was higher than that of the low exposure group (p < 0.05). However, the micronucleus frequency and frequencies of GSTP1 (Ile105Val) polymorphisms among the 2 groups did not significantly differ. Furthermore, among these 3 biomarkers, only DNA damage was associated with formaldehyde exposure (P <0.05).

Conclusions: Based on these findings, assessing DNA damage using Comet assay is recommended as a biomarker of occupational exposure to formaldehyde and health surveillance.

Key words: Embalmers, Formaldehyde, Micronucleus, DNA Damage, GSTP1 gene polymorphism

References

[1] International Agency for Research on Cancer [IARC]. Chemical agents and related occupations 2012. [cited 2018 August 10]. Available from: https://monographs.iarc.fr/wp-content/uploads/2018/06/mono100F.pdf.

[2] Chiarella P, Tranfo G, Pigini D, Carbonari D. Is it possible to use biomonitoring for the quantitative assessment of formaldehyde occupational exposure? Biomark Med. 2016;10(12):1287-303. doi: 10.2217/bmm-2016-0146

[3] World Health Organization [WHO]. WHO Guidelines for indoor air quality: selected pollutants 2010. [cited 2022 April 25]. Available from: http://www.euro. who.int/__data/assets/pdf_file/0009/128169/e94535.pdf.

[4] Nielsen GD, Larsen ST, Wolkoff P. Re-evaluation of the WHO (2010) formaldehyde indoor air quality guideline for cancer risk assessment. Arch Toxicol. 2017;91(1):35-61. doi: 10.1007/s00204-016-1733-8

[5] Casarett LJ, Doull J, Klaassen CD. Casarett and Doull's toxicology: the basic science of poisons. 8th ed. New York : McGraw-Hill Education; 2013.

[6] National Cancer Institute [NIH]. Formaldehyde and cancer risk. [cited 2024 April 25]. Available from: https://www.cancer.gov/about-cancer/causes-prevention/risk/substances/formaldehyde.

[7] National Toxicology Program. Formaldehyde, Report on Carcinogens, Fifteenth Edition. [cited 2024 April 25]. Available from: https://ntp.niehs.nih.gov/whatwestudy/assessments/cancer/roc.

[8] United States Environmental Protection Agency [EPA]. Formaldehyde. [cited 2024 April 24]. Available from: https://www.epa.gov/

[9] Kawanishi M, Matsuda T, Yagi T. Genotoxicity of formaldehyde: molecular basis of DNA damage and mutation. Front Environ Sci. 2014;2. doi: 10.3389/fenvs.2014.00036

[10] Klages-Mundt NL, Li L. Formation and repair of DNA-protein crosslink damage. Sci China Life Sci. 2017;60(10):1065-76. doi: 10.1007/s11427-017-9183-4

[11] Hoffman EA, Frey BL, Smith LM, Auble DT. Formaldehyde crosslinking: a tool for the study of chromatin complexes. J Biol Chem. 2015;290(44):26404-11. doi: 10.1074/jbc.R115.651679

[12] Hopf NB, Bolognesi C, Danuser B, Wild P. Biological monitoring of workers exposed to carcinogens using the buccal micronucleus approach: A systematic review and meta-analysis. Mutat Res Rev Mutat Res. 2019;781:11-29. doi: 10.1016/j.mrrev.2019.02.006

[13] Fenech M, Knasmueller S, Bolognesi C, Bonassi S, Holland N, Migliore L, et al. Molecular mechanisms by which in vivo exposure to exogenous chemical genotoxic agents can lead to micronucleus formation in lymphocytes in vivo and ex vivo in humans. Mutat Res Rev Mutat Res. 2016;770(Pt A):12-25. doi: 10.1016/j.mrrev.2016.04.008

[14] Swenberg JA, Lu K, Moeller BC, Gao L, Upton PB, Nakamura J, et al. Endogenous versus exogenous DNA adducts: their role in carcinogenesis, epidemiology, and risk assessment. Toxicol Sci. 2011;120(Suppl 1):S130-45. doi: 10.1093/toxsci/kfq371

[15] Zhong W, Que Hee SS. Formaldehyde-induced DNA adducts as biomarkers of in vitro human nasal epithelial cell exposure to formaldehyde. Mutat Res. 2004;563(1):13-24. doi: 10.1016/j.mrgentox.2004.05.012

[16] Lu K, Collins LB, Ru H, Bermudez E, Swenberg JA. Distribution of DNA adducts caused by inhaled formaldehyde is consistent with induction of nasal carcinoma but not leukemia. Toxicol Sci. 2010;116(2):441-51. doi: 10.1093/toxsci/kfq061

[17] Leng J, Liu CW, Hartwell HJ, Yu R, Lai Y, Bodnar WM, et al. Evaluation of inhaled low-dose formaldehyde-induced DNA adducts and DNA-protein cross-links by liquid chromatography-tandem mass spectrometry. Arch Toxicol. 2019;93(3):763-73. doi: 10.1007/s00204-019-02393-x

[18] Yu R, Lai Y, Hartwell HJ, Moeller BC, Doyle-Eisele M, Kracko D, et al. Formation, accumulation, and hydrolysis of endogenous and exogenous formaldehyde-Induced DNA Damage. Toxicol Sci. 2015;146(1):170-82. doi: 10.1093/toxsci/kfv079

[19] Luzhna L, Kathiria P, Kovalchuk O. Micronuclei in genotoxicity assessment: from genetics to epigenetics and beyond. Front Genet. 2013;4:131. doi: 10.3389/fgene.2013.00131

[20] Bolognesi C, Bonassi S, Knasmueller S, Fenech M, Bruzzone M, Lando C, et al. Clinical application of micronucleus test in exfoliated buccal cells: A systematic review and metanalysis. Mutat Res Rev Mutat Res. 2015;766:20-31. doi: 10.1016/j.mrrev.2015.07.002

[21] Zendehdel R, Vahabi M, Sedghi R. Estimation of formaldehyde occupational exposure limit based on genetic damage in some Iranian exposed workers using benchmark dose method. Environ Sci Pollut Res Int. 2018;25(31):31183-9. doi: 10.1007/s11356-018-3077-9

[22] Costa S, Pina C, Coelho P, Costa C, Silva S, Porto B, et al. Occupational exposure to formaldehyde: genotoxic risk evaluation by comet assay and micronucleus test using human peripheral lymphocytes. J Toxicol Environ Health A. 2011;74(15-16):1040-51. doi: 10.1080/15287394.2011.582293

[23] Costa S, Coelho P, Costa C, Silva S, Mayan O, Santos LS, et al. Genotoxic damage in pathology anatomy laboratory workers exposed to formaldehyde. Toxicology. 2008;252(1-3):40-8. doi: 10.1016/j.tox.2008.07.056

[24] Rojas E, Lorenzo Y, Haug K, Nicolaissen B, Valverde M. Epithelial cells as alternative human biomatrices for comet assay. Front Genet. 2014;5:386. doi: 10.3389/fgene.2014.00386

[25] Singh Z. Comet assay as a sensitive technique in occupational health studies; A literature review. JOHE. 2018;7(4):240-5. doi: 10.29252/johe.7.4.240

[26] Zendehdel R, Abdolmaleki P, Jouni FJ, Mazinani M. Genetic variation and risk of DNA damage in peripheral blood lymphocytes of Iranian formaldehyde-exposed workers. Hum Exp Toxicol. 2018;37(7):690-6. doi: 10.1177/0960327117728385

[27] Costa S, Costa C, Madureira J, Valdiglesias V, Teixeira-Gomes A, Guedes de Pinho P, et al. Occupational exposure to formaldehyde and early biomarkers of cancer risk, immunotoxicity and susceptibility. Environ Res. 2019;179(Pt A):108740. doi: 10.1016/j.envres.2019.108740

[28] Costa S, Carvalho S, Costa C, Coelho P, Silva S, Santos LS, et al. Increased levels of chromosomal aberrations and DNA damage in a group of workers exposed to formaldehyde. Mutagenesis. 2015;30(4):463-73. doi: 10.1093/mutage/gev002

[29] Jiang S, Yu L, Cheng J, Leng S, Dai Y, Zhang Y, et al. Genomic damages in peripheral blood lymphocytes and association with polymorphisms of three glutathione S-transferases in workers exposed to formaldehyde. Mutat Res. 2010;695(1-2):9-15. doi: 10.1016/j.mrgentox.2009.09.011

[30] Peteffi GP, da Silva LB, Antunes MV, Wilhelm C, Valandro ET, Glaeser J, et al. Evaluation of genotoxicity in workers exposed to low levels of formaldehyde in a furniture manufacturing facility. Toxicol Ind Health. 2016;32(10):1763-73. doi: 10.1177/0748233715584250

[31] Eshkoor SA, Ismail P, Rahman SA, Moin S. Does GSTP1 polymorphism contribute to genetic damage caused by ageing and occupational exposure? Arh Hig Rada Toksikol. 2011;62(4):291-8. doi: 10.2478/10004-1254-62-2011-2088

[32] Schlesselman JJ, Stolley PD. Case-control studies: design, conduct, analysis. New York: Oxford University Press, 1982.

[33] Viegas S, Ladeira C, Nunes C, Malta-Vacas J, Gomes M, Brito M, et al. Genotoxic effects in occupational exposure to formaldehyde: A study in anatomy and pathology laboratories and formaldehyde-resins production. J Occup Med Toxicol. 2010;5(1):25. doi: 10.1186/1745-6673-5-25

[34] The National Institute for Occupational Safety and Health [NIOSH]. NIOSH Manual of Analytical Methods (NMAM). 5th ed. [cited 2018 April]. Available from: https://www.cdc.gov/niosh/nmam/ method-f.html.

[35] Hornung RW, Reed LD. Estimation of average concentration in the presence of nondetectable values. Appl Occup Environ Hyg. 1990;5(1):46-51. doi: 10.1080/1047322X.1990.10389587

[36] Speit G, Schmid O, Fröhler-Keller M, Lang I, Triebig G. Assessment of local genotoxic effects of formaldehyde in humans measured by the micronucleus test with exfoliated buccal mucosa cells. Mutat Res. 2007;627(2):129-35. doi: 10.1016/j.mrgentox.2006.10.013

[37] Lorenzoni DC, Pinheiro LP, Nascimento HS, Menegardo CS, Silva RG, Bautz WG, et al. Could formaldehyde induce mutagenic and cytotoxic effects in buccal epithelial cells during anatomy classes? Med Oral Patol Oral Cir Bucal. 2017;22(1):e58-e63. doi: 10.4317/medoral.21492

[38] Thomas P, Holland N, Bolognesi C, Kirsch-Volders M, Bonassi S, Zeiger E, et al. Buccal micronucleus cytome assay. Nat Protoc. 2009;4(6):825-37. doi: 10.1038/nprot.2009.53

[39] Holland N, Bolognesi C, Kirsch-Volders M, Bonassi S, Zeiger E, Knasmueller S, et al. The micronucleus assay in human buccal cells as a tool for biomonitoring DNA damage: the HUMN project perspective on current status and knowledge gaps. Mutat Res. 2008;659(1-2):93-108. doi: 10.1016/j.mrrev.2008.03.007

[40] Pala M, Ugolini D, Ceppi M, Rizzo F, Maiorana L, Bolognesi C, et al. Occupational exposure to formaldehyde and biological monitoring of Research Institute workers. Cancer Detect Prev. 2008;32(2):121-6. doi: 10.1016/j.cdp.2008.05.003

[41] Ramos MA, Cury Fde P, Scapulatempo Neto C, Marques MM, Silveira HC. Micronucleus evaluation of exfoliated buccal epithelial cells using liquid-based cytology preparation. Acta Cytol. 2014;58(6):582-8. doi: 10.1159/000366224

[42] Ladeira C, Viegas S, Carolino E, Prista J, Gomes MC, Brito M. Genotoxicity biomarkers in occupational exposure to formaldehyde--the case of histopathology laboratories. Mutat Res. 2011;721(1):15-20. doi: 10.1016/j.mrgentox.2010.11.015

[43] Cavallo D, Ursini CL, Rondinone B, Iavicoli S. Evaluation of a suitable DNA damage biomarker for human biomonitoring of exposed workers. Environ Mol Mutagen. 2009;50(9):781-90. doi: 10.1002/em.20501

[44] Metgud R, Neelesh BT. Effect of staining procedures on the results of micronucleus assay in the exfoliated buccal mucosal cells of smokers and nonsmokers: A pilot study. J Cancer Res Ther. 2018;14(2):372-6. doi: 10.4103/0973-1482.157351

[45] Chandirasekar R, Kumar BL, Sasikala K, Jayakumar R, Suresh K, Venkatesan R, et al. Assessment of genotoxic and molecular mechanisms of cancer risk in smoking and smokeless tobacco users. Mutat Res Genet Toxicol Environ Mutagen. 2014;767:21-7. doi: 10.1016/j.mrgentox.2014.04.007

[46] Singh NP, McCoy MT, Tice RR, Schneider EL. A simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res. 1988;175(1):184-91. doi: 10.1016/0014-4827(88)90265-0

[47] The National Institute for Occupational Safety and Health [NIOSH]. NIOSH Pocket Guide to Chemical Hazards 2018. [cited 2022 April 25]. Available from: https://www.cdc.gov/niosh/npg/npgd0294.html.

[48] Department of Labour Protection and Welfare. The announcement of Department of Labour Protection and Welfare: Thailand hazardous chemicals exposure limit B.E. 2560. [cited 2022 April 25]. Available from: http://cste.sut.ac.th/csteshe/wp-content/lews/Law28.pdf.

[49] Ghelli F, Cocchi E, Bellisario V, Buglisi M, Squillacioti G, Santovito A, et al. The formation of SCEs as an effect of occupational exposure to formaldehyde. Arch Toxicol. 2022;96(4):1101-8. doi: 10.1007/s00204-022-03238-w

[50] Wojda A, Zietkiewicz E, Witt M. Effects of age and gender on micronucleus and chromosome nondisjunction frequencies in centenarians and younger subjects. Mutagenesis. 2007;22(3):195-200. doi: 10.1093/mutage/gem002

[51] Lin D, Guo Y, Yi J, Kuang D, Li X, Deng H, et al. Occupational exposure to formaldehyde and genetic damage in the peripheral blood lymphocytes of plywood workers. J Occup Health. 2013;55(4):284-91. doi: 10.1539/joh.12-0288-oa

Download

Share

COinS