Biomarkers of susceptibility and effect in car painters exposed to organic solvents
Abstract
Introduction: Car painters are routinely exposed to organic solvents classified as carcinogenic and mutagenic substances.
Objective: To characterize the population susceptibility and evaluate the genotoxic effects of exposure to organic solvents.
Methods: A cross-sectional study comparing a group of car painters exposed to organic solvents with a non-exposed group. CYP2E1 polymorphisms and the presence of micronuclei in lymphocytes were determined.
Results: One hundred twenty-two workers participated in the study: 62 who worked in car paint shops and were exposed to solvents, and 60 who were not exposed. There were statistically significant differences between the two groups regarding micronucleated cells and nucleoplasmic bridges frequencies (p=0.042 and p=0.046, respectively; exact likelihood ratio). Significant differences were found at the interaction between the CYP2E1 genotype c1c1 and occupational exposure to solvents, with higher frequencies of micronuclei (p= 0.013) and micronucleated cells (p= 0.015). However, when the frequencies of micronuclei, micronucleated cells and nucleoplasmic bridges in the exposure group were compared between the c1c1 and c2c2/c1c2 allele groups of the CYP2E1 polymorphism, statistically significant differences were found.
Conclusions: This study confirms that when workers with CYP2E1 polymorphisms, specifically the c1c1 genotype, are exposed to organic solvents, they are more likely to have somatic cell mutations, a condition associated with increased susceptibility to diseases such as cancer
Authors
Downloads
Keywords
- occupational exposure
- micronucleus test
- genetic polymorphism
- benzene
- toluene
- xylene
- Solvents
- Methylene Chloride
- Acetone
- Reactive Oxygen Species
- Teratogens
- Mutagens
References
Environmental Protection Agency. Hazardous Waste Management System; Identification and Listing of Hazardous Waste; Paint Production Wastes. EPA; 2001; 66(30). Disponible en: https://www.gpo.gov/fdsys/pkg/FR-2001-02-13/pdf/01-3087.pdf
Costa C, Pasquale RD, Silvari V, Barbaro M, Catania S. In Vitro evaluation of oxidative damage from organic solvent vapours on human skin. Toxicol in Vitro. 2006; 20:324-331. https://doi.org/10.1016/j.tiv.2005.08.007
Mattia C, Lebel C, Bondy S. Effect of toluene and its metabolites on cerebral reactive oxygen species generation. Biochem Pharmacol. 1991; 42:879-882. https://doi.org/10.1016/0006-2952(91)90048-A
Heuser V. Evaluation of genetic damage in Brazilian footwear-workers: biomarkers of exposure, effect and susceptibility. Toxicology. 2007; 10:1-13. https://doi.org/10.1016/j.tox.2007.01.011
Bonassi S, Neri M, Puntoni R. Validation of biomarkers as early predictors of disease. Mutat Res. 2001; 480-481:349-358. https://doi.org/10.1016/S0027-5107(01)00194-4
Swanepoel AJ. Evaluation of DNA damage and DNA repair by the comet assay in workers exposed to organic solvents. [M.Sc. Thesis]. North-West University, Potchefstroom Campus, 2004. Disponible en: http://hdl.handle.net/10394/1482
Zhu CQ, Lam TH, Jiang CQ. Lymphocyte DNA damage in bus manufacturing workers. Mutat Res. 2001; 491:173-181. https://doi.org/10.1016/S1383-5718(01)00141-3
IARC (International Agency for Research on Cancer). Occupational exposure as a painter. IARC Monographs on the Evaluation of the Carcinogenic Risks of Chemicals to Humans IARC. 2010; 98:509-539. Disponible en: http://monographs.iarc.fr/ENG/Monographs/vol98/mono98-6.pdf
Fenech M, Chang WP, Kirsch-Volders M, Holland N, Bonassi S, Zeiger E. HUMN project: detailed description of the scoring criteria for the cytokinesis-block micronucleus assay using isolated human lymphocyte cultures. Mutat Res. 2003; 534:65-75. https://doi.org/10.1016/S1383-5718(02)00249-8
Fenech M, Bonassi S. The effect of age, gender, diet and lifestyle on DNA damage measured using micronucleus frequency in human peripheral blood lymphocytes. Mutagenesis. 2011; 26(1):43-49. https://doi.org/10.1093/mutage/geq050
Fenech M, Crott J, Turner J, Brown S. Necrosis, apoptosis, cytostasis and ADN damage in human lymphocytes measured simultaneously within the cytokinesis-block micronucleus assay: description of the method and results for hydrogen peroxide. Mutagenesis. 1999; 14(6):605-612. DOI: 10.1093/mutage/14.6.605
https://doi.org/10.1093/mutage/14.6.605
Nersesyan A, Fenech M, Bolognesi C, Mišík M, Setayesh T, Wultsch G, et al. Use of the lymphocyte cytokinesis-block micronucleus assay in occupational biomonitoring of genome damage causes by in vivo exposure to chemical genotoxins: Past, present and future. Mutat Res. 2016; 770:1-11. https://doi.org/10.1016/j.mrrev.2016.05.003
Heuser V, Moraes V, Da Silva J, Erdtmann B. Comparison of genetic damage in Brazilian footwear-workers exposed to solvent-based or water-based adhesive. Mutat Res. 2005; 583(1):85-94. https://doi.org/10.1016/j.mrgentox.2005.03.002
Pitarque M, Vaglenov A, Nosko M, Hirvonen A, Norppa H, Creus A, Marcos R. Evaluation of ADN damage by the comet assay in shoe workers exposed to toluene and other organic solvents. Mutat Res. 1999; 441:115-127. https://doi.org/10.1016/S1383-5718(99)00042-X
Roma-Torres J, Teixeira JP, Silva S, Laffon B, Cunha LM, Mendez J, et al. Evaluation of genotoxicity in a group of workers from a petroleum refinery aromatics plant. Mutat Res. 2006; 604:19-27. https://doi.org/10.7705/biomedica.4289
Iravathy K, Shankarapppa K, Vijayashree B, Prabhakar K, Ahuja YR. DNA damage and repair studies in individuals working with photocopying machines. IJHG. 2001; 1(2):139-143. https://doi.org/10.1080/09723757.2001.11885749
https://doi.org/10.1080/09723757.2001.11885749
Sul D, Lee E, Lee MY, Kang SK. ADN damage in lymphocytes of benzene exposed workers correlates with trans, trans-muconic acids and breath benzene levels. Mutat Res. 2005; 582:61-70. https://doi.org/10.1016/j.mrgentox.2004.12.011
Hayashi S, Watanabe J, Kawajiri K. Genetic polymorphisms in the 5'-flanking region change transcriptional regulation of the human cytochrome P450IIE1 gene. J. Biochem. 1991; 110:559-565. https://doi.org/10.1093/oxfordjournals.jbchem.a123619
Bolt HM, Roos PH, Their R. The cytochrome P-450 isoenzyme CYP2E1 in the biological processing of industrial chemicals: consequences for occupational and environmental medicine. Int Arch Occup Environ Health. 2003; 76:174-185. https://doi.org/10.1007/s00420-002-0407-4
Hoyos-Giraldo LS, Escobar-Hoyos LF, Saavedra-Trujillo D, Reyes-Carvajal I, Muñoz A, Londoño-Velasco E, et al. Gene-specific promoter methylation is associated with micronuclei frequency in urothelial cells from individuals exposed to organic solvents and paints. J Expo Sci Environ Epidemiol. 2016; 26(3):257‐262. https://doi.org/10.1038/jes.2015.28
Londoño-Velasco E, Martínez-Perafán F, Carvajal-Varona S, García-Vallejo F, Hoyos-Giraldo LS. Assessment of DNA damage in car spray painters exposed to organic solvents by the high-throughput comet assay. Toxicol Mech Methods. 2016; 26(4):238-242. https://doi.org/10.3109/15376516.2016.1158892
Villalba-Campos M, Chuaire-Noack L, Sánchez-Corredor MC, Rondón-Lagos M. High chromosomal instability in workers occupationally exposed to solvents and paint removers. Mol Cytogenet. 2016; 9:46. DOI 10.1186/s13039-016-0256-6 https://doi.org/10.1186/s13039-016-0256-6
Villalba-Campos M, Ramírez-Clavijo SR, Sánchez-Corredor MC, Rondón-Lagos M, Ibáñez-Pinilla M, Palma RM, et al. Quantification of cell-free DNA for evaluating genotoxic damage from occupational exposure to car paints. J Occup Med Toxicol. 2016; 11:33. https://doi.org/10.1186/s12995-016-0123-8
Guo YM, Wang Q, Liu YZ, Chen HM, Qi Z, Guo QH. Genetic polymorphisms in cytochrome P4502E1, alcohol and aldehyde dehydrogenases and the risk of esophageal squamous cell carcinoma in Gansu Chinese males. World J Gastroenterol 2008; 14(9):1444-1449. https://doi.org/10.3748/wjg.14.1444
Cleves MA.Hardy-Weinberg Equilibrium Tests and Allele Frequency Estimation. STATA Technical Bulletin. No. 48. March 1999, 34-37. https://doi.org/10.1161/ATVBAHA.107.153981
Varona M, Narváez D, Groot H, Combariza D. Biomarcadores y genotoxicidad. En: Rodriguez C. Toxicología ocupacional. 1Aed. Bogotá: Sociedad Colombiana de Medicina del Trabajo; 2013. P.307-29.
Torres C, Varona M, Lancheros A, Patiño R, Groot H. Evaluación del daño en el ADN y vigilancia biológica de la exposición laboral a solventes orgánicos. Biomédica. 2008; 28:126-38. https://doi.org/10.7705/biomedica.v28i1.115
Hoyos-Giraldo LS, Carvajal S, Cajas-Salazar N, Ruiz M, Sánchez-Gómez A. Chromosome aberrations in workers exposed to organic solvents: Influence of polymorphisms in xenobiotic-metabolism and DNA repair genes. Mutat Res. 2009; 666(1-2):8-15. https://doi.org/10.1016/j.mrfmmm.2009.03.003
Ministerio de Trabajo de la República de Colombia. Recomendaciones Guía de atención integral de Seguridad y Salud en el Trabajo para trabajadores expuestos a benceno y sus derivados. Bogotá. 2015. Disponible en: https://www.mintrabajo.gov.co/web/guest/relaciones-laborales/comision-permanente-de-concertacion/-/document_library/mRRfCPNbtpih/view_file/60364
Harrison RJ, Roisman R. Disolventes. En: Ladou J, Harrison R. Diagnóstico y tratamiento en medicina laboral y ambiental. 5 ed. Mexico, D.F: Editorial El Manual Moderno; 2015. P.524-56.
León-Mejía G, Espitia-Pérez L, Hoyos-Giraldo LS, Da Silva J, Hartmann A, Pêgas Henriques JA, et al. Assessment of DNA damage in coal open-cast mining workers using the cytokinesis-blocked micronucleus test and the comet assay. Sci Total Environ. 2011;409(4):686-691. DOI: 10.1016/j.scitotenv.2010.10.049
https://doi.org/10.1016/j.scitotenv.2010.10.049
Ulusoy G, Arinç E, Adali O. Genotype and allele frequencies of polymorphic CYP2E1 in the Turkish population. Arch. Toxicol. 2007; 81(10):711-18. https://doi.org/10.1007/s00204-007-0200-y
Dahlström V, Erdtmann B, Kvitko K, Rohr P, da Silva J. Evaluation of genetic damage in Brazilian footwear-workers: Biomarkers of exposure, effect, and susceptibility. Toxicology. 2007; 232(3):235-47. https://doi.org/10.1093/mutage/gen031
Tsutsumi M Wang JS, Takase SA, Takada. Hepatic messenger RNA contents of cytochrome P4502E1 in patients with different P450 2E1 genotypes. Alcohol. 1994; 29:29-32. https://doi.org/10.1016/0928-4346(94)90046-9
Atkinson AJ Jr., & Markey SP. Biochemical mechanisms of drug toxicity. Chapter 16. In: Atkinson AJ Jr., Huang S-M, Lertora JJL, & Markey SP. Principles of Clinical Pharmacology. Academic Press. 2012. https://doi.org/10.1016/B978-0-12-385471-1.00016-7
Cheong HSJ, Seth I, Joiner MC, Tucker JD. Relationships Among Micronuclei, Nucleoplasmic Bridges and Nuclear Buds Within Individual Cells in the Cytokinesis-Block Micronucleus Assay. Mutagenesis, 2013; 28:433-440. https://doi.org/10.1093/mutage/get020
Copyright (c) 2020 Marcela Varona-Uribe, Milciades Ibáñez-Pinilla, Leonardo Briceno-Ayala, Diego Herrera, Lilian Chuaire-Noack, María Martínez-Agüero, Magda Carolina Sánchez Corredor, Ruth Palma-Parra, Diana Narvaéz, Helena Groot de Restrepo
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
The copy rights of the articles published in Colombia Médica belong to the Universidad del Valle. The contents of the articles that appear in the Journal are exclusively the responsibility of the authors and do not necessarily reflect the opinions of the Editorial Committee of the Journal. It is allowed to reproduce the material published in Colombia Médica without prior authorization for non-commercial use
