DNA damage assessment and biological monitoring of occupational exposure to organic solvents, 2006
Keywords:
DNA damage/genetics, occupational exposure, solvents/toxicity, public health
Abstract
Introduction. Exposure to solvents is one of the highest potential risks for millions of workers in the world; they can generate substantial environmental pollution leading to outbreaks of public health problems.Objective. Blood levels were determined for metabolites of benzene, toluene and xylene, and polymorphisms for enzymes CYP2E1, GSTM1, GSTT1 were characterized. Damage to DNA was assessed by the comet assay for exposure to organic solvents.
Materials and methods. A cross-sectional study was undertaken in 90 employees from 5 different companies. A survey form was administered; blood was sampled to detect the genetic polymorphisms and to apply the comet assay (single cell gel electrophoresis) to detect DNA fragmentation. The concentrations of phenol, ortho and meta methylhippuric acids were measured in urine. Statistical analyses explored the possible associations.
Results. The percentage of workers directly exposed to solvents was 34.4%. In this group, the evidence indicated concentrations higher than the permitted limits: 3.3% for phenol, 6.6% for hippuric acid, 3.3% for ortho-methylhippuric acid and 36.7% for metamethylhippuric acid. In the Comet assay, the length of the comets tail was greater than average (19.5 ìm) in exposed subjects, and the percentage of cells with mild damage (19.0%) (p=0.0007) was higher. The percentage of exposed individuals with absent genotypes for enzymes GSTT1 and GSTM1 was 46.7% and 56.8% respectively.
Conclusion. Exposure biomarkers have become fundamental tools for the evaluation of risk associated with exposure to toxic agents.
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References
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13. Olsson H, Brand L. Occupation exposure to organic solvents and Hodking´s disease in man. Scand J Work Environ Health. 1980;6:302-5.
14. Langman JM. Xylene: its toxicity, measurement of exposure levels, absorption, metabolism and clearance. Pathology. 1994;26:301-9.
15. Chen Z, Liu SJ, Cai SX, Yao YM, Yin H, Ukai H, et al. Exposure of workers to a mixture of toluene and xylenes. II Efects. Occup Environ Med. 1994;51:47-9.
16. Ukai H, Takada S, Inui S, Imai Y, Kawai T, Shimbo S, et al. Occupational exposure to solvent mixtures: effects on health and metabolism. Occup Environ Med. 1994;51:523-9.
17. Yardley-Jones A, Anderson D, Lovell DP, Jenkinson PC. Analysis of chromosomal aberrations in workers exposed to low level benzene. Br J Ind Med. 1990;47:48-51.
18. Eastmond DA, Tucker JD. Identification of aneuploidy-inducing agents using citokinesis-blocked human lymphocytes and an antikinetochore antibody. Environ Mol Mutagen. 1989;13:34-43.
19. Major J, Jakab M, Kiss G, Tompa A. Chromosome aberration, sister-chromatid exchange, proliferative rate index, and serum thiocyanate concentration in smokers exposed to low-dose benzene. Environ Mol Mutagen. 1994;23:137-42.
20. van Damme K, Casteleyn L, Heseltine E, Huici A, Sorsa M, van Larebeke N, et al. Individual susceptibility and prevention of occupational diseases: scientific and ethical issues. J Occup Environ Med. 1995;37:91-9.
21. McKelvey-Martin VJ, Green MH, Schmezer P, Pool-Zobel BL, De Méo MP, Collins A. The single cell gel electrophoresis assay (comet assay): an European review. Mutat Res. 1993;288:47-63.
22. Anderson D, Yu TW, Schmezer P. The effect of various antioxidants and the other modifying agents on oxygen-radical-generated DNA damage in human lymphocytes in the comet assay. Mutat Res. 1994; 307:261-71.
23. Collins A, Dusinská M, Franklin M, Somorovská M, Petrovská H, Duthie S, et al. Comet assay in human biomonitoring studies. Reliability, validation and applications. Environ Mol Mutagen. 1997;30:139-46.
24. Hartmann A, Speit G. Genotoxic effects of chemicals in the single cell gel (SCG) test with human blood cell in relation to the induction of sister chromatid exchanges (SCE). Mutat Res. 1995;346:49-56.
25. Pfuhler S, Wolf HU. Detection of DNA-crosslinking agents with the alkaline comet assay. Environ Mol Mutagen.1996;27:196-201.
26. Fairbairn DW, Olive PL, O´Neill KL. The comet assay: a comprehensive review. Mutat Res. 1995;339:37-59.
27. Collins AR, Duthie SJ, Dobson VL. Direct enzymic detection of endogenous oxidative base damage in human lymphocyte DNA. Carcinogenesis. 1993; 14:1733-5.
28. Hartmann A, Speit G. Comparative investigations of genotoxic effects of metals in the single cell gel (SCG) assay and the sister chromatid exchange (SCE) test. Environ Mol Mutagen. 1994;23:299-305.
29. Speit G, Hanelt S, Helbig R, Seidel A, Hartmann A. Detection of DNA effects in human cells with the comet assay and their relevance for mutagenesis. Toxicol Lett. 1996;88:91-8.
30. Plappert U, Barthel E, Seidel HJ. Reduction of benzene toxicity by toluene. Environ Mol Mutagen. 1994;24:283-92.
31. Pool-Zobel BL Lotzmann N, Knoll M, Kuchenmeister F, Lambertz R, Leucht U, Schröder HG, et al. Detection of genotoxic effects in human gastric and nasal mucosa cells isolated from biopsy samples. Environ Mol Mutagen. 1994;24:23-45.
32. Fuscoe JC, Afshari A, George M, De Angelo AB, Tice RR, SalmanT, et al. In vivo genotoxicity of dichloroacetic acid: Evaluation with the mouse peripheral blood micronucleus assay and the single cell gel assay. Environ Mol Mutagen. 1996;27:1-9.
33. Betti C, Davini T, Giannessi L, Loprieno N, Barale R. Microgel electrophoresis assay (comet test) and SCE analysis in human lymphocytes from 100 normal subjects. Mutat Res. 1994;307:323-33.
34. Green MH, Lowe JE, Waugh AP, Aldridge KE, Cole J, Arlett CF. Effect of diet and vitamin c on DNA strand breakage in freshly-isolated human blood cells. Mutat Res. 1994;316:91-102.
35. Tice RR. The single cell gel/comet: A microgel electrophoretic technique for the detection of DNA damage and repair in individual cell. En: Phillips DH, Venitt S, editors. Environmental mutagenesis. Oxford: Bios Scientific; 1995. p.315-39.
36. Dennong C, Hartmann A, Frey G, Speit G. Detection of DNA damage after hyperbaric oxygen (HBO) therapy. Mutagenesis. 1996;11:605-9.
37. Tice RR, Strauss GH, Peters WP. High-dose combination alkylating agents with autologous bone-marrow support in patients with breast cancer: preliminary assessment of DNA damage in individual peripheral blood lymphocytes using the single cell gel electrophoresis assay. Mutat Res. 1992;271:101-13.
38. GediK CM, Ewen SW, Collins AR. Single-cell electrophoresis applied to the analysis of UV-C damage and its repair in human cell. Int J Radiat Biol. 1992;62:313-20.
39. Green MH, Lowe JE, Harcourt SA, Akinluyi P, Rowe T, Cole J, et al. Sensitivity of unstimulated and stimulated human lymphocytes from normal and xeroderma pigmentosum donors in the comet assay. A potential diagnostic technique. Mutat Res. 1992;273:137-44.
40. Vijayalaxmi, Tice RR, Strauss GH. Assessment of radiation-induced DNA damage in human blood lymphocytes using the single-cell gel electrophoresis technique. Mutat Res. 1992; 271:243-52.
41. Matthias C, Bockmuhl U, Jahnke V, Jones P, Hayes J, Alldersea J, et al. Polymorphism in cytochrome P450 CYP2D6, CYP1A1, CYP2E1 an glutathione S-transferase, GSTM1, GSTM3, GSTT1 and susceptibility to tobacco-related cancers: studies in upper aerodigestive tract cancers. Pharmacogenetics. 1998;8:91-110.
42. Tomatis L, Aitio A, Wilbourn J, Shuker L. Human carcinogens so far identified. Jpn J Cancer Res. 1989;80:795-807.
43. Sing NP, McCoy MT, Tice RR, Schneider EL. A simple technique for quantization of low levels of DNA damage in individual cells. Exp Cell Res.1988;175:184-91.
44. Hayashi SI, Watanabe J, Kawajiri K. Genetic polymorphism in the 5-flanking region change the transcriptional regulation of the human CYP2E1 gene. J Biochem (Tokyo). 1991;110:559-65.
45. Hirvonen A, Husgafvel-Pursiainen K, Antilla S, Karjallainen A, Vainio H. The human CYP2E1 gene and lung cancer: Dra1 and Rsa1 restriction fragment length polymorphism in a Finnish study population. Carcinogenesis. 1993;14:85-8.
46. The National Institute for Occupational Safety and Health (NIOSH). Hippuric and methyl hippuric acids in urine. Method 8301, issue 3. Date: 15 March 2003. [Consultado: 5 de diciembre de 2005]. Disponible en: http://www.cdc.gov/Niosh/nmam/pdfs/8301.pdf
47. Acosta H. Determinación de fenol y ácidos hipúrico y metil hipúrico en orina mediante técnicas cromatográficas (GC-FID y HPLC-UV). Manual de procedimientos. Bogotá: Instituto Nacional de Salud; 1996.
48. Axency for Toxic Substances and Disease Registry.Xileno. CAS #1330-20-7. September 2005. Consultado: 5 de diciembre de 2005. Disponible en: http://www.atsdr.cdc.gov/es/toxfaqs/es_tfacts71.pdf
49. Instituto Nacional de Seguridad e Higiene en el Trabajo.Tabla 5 - Valores límite biológicos, VLBs. Consultado: 5 de diciembre de 2005. Disponible en: http://www.mtas.es/insht/practice/vlb.htm
50. Gonzalez C, Sala N, Capella G. Minireview. Genetic susceptibility and gastric cancer risk. Int J Cancer. 2002;100: 249-60.
51. Torres M, Acosta C, Sicard D, Groot H. Susceptibilidad genética y riesgo de cáncer gástrico en una población del Cauca. Biomédica. 2004;24:153-62.
52. Au W, Lee E, Christiani DC. Biomarker research in occupational health. J Occup Environ Med. 2005;47:145-53.
2. Organización Mundial de la Salud. Límites recomendados por razones de salud en la exposición profesional a determinados solventes orgánicos. Serie de informes técnicos 664. Ginebra: Editorial Gráficas Unidas S.A.; 1982. p.28-43.
3. Seedorft L, Olsen E. Exposure to organics solvents. A survey on the use of solvents. An Occup Hyg. 1990;34:371-8.
4. Córdoba D. Toxicología. Cuarta edición. Bogotá: Editorial El Manual Moderno; 2000. p.601-10.
5. Medinsky MA, Kenyon EM, Seaton MJ, Schlosser PM. Mechanistic considerations in benzene physiological model development. Environ Health Perspect. 1996;104(Suppl.6):1399-404.
6. DAzevedo PA, Tannhauser M, Tannhauser SL, Barros HM. Hematological alterations in rats from xylene and benzene. Vet Human Toxicol. 1996;38:340-4.
7. Peña G, Varona M, Acosta H, Cárdenas O, Sanchez C, Cardozo M, et al. Evaluación epidemiológica de la exposición a solventes orgánicos en fábricas de pinturas y pegantes en Santa Fe de Bogotá. Documento técnico. Bogotá: Instituto Nacional de Salud; 1996. p.1-28.
8. Mayor J, Saiz J, Eimil E, Beguería R, Palomino A, Charró L. Estudio de los efectos sobre el sistema nervioso de la exposición potencial a solventes orgánicos. Documento técnico. Bogotá: Instituto de Seguros Sociales; 1998.
9. Varona M, Cárdenas O, Conde JV, Rossi L, Idrovo AJ, Araque A, et al. Determinación de la exposición en trabajadores que laboran con solventes orgánicos en Santa Fe de Bogotá 2000. Documento técnico. Bogotá: Instituto Nacional de Salud; 2001. p.1-34.
10. Goldfrank LR, Lewin NA, Flomenbaun EN. Toxicologic emergencies. Conneticut: Edit. Appleton Century Crofts; 1986. p.672-85.
11. Casarett L, Doull J. Organochlorine Insecticides. Toxicology, the basic science of poisons. Fourth edition. New York: Macmillan Publishing Co; 1991. p. 681-722.
12. Meulenbelt J, De Groot G, Savelkoul TJ. Two cases of acute toluene intoxication. Br J Ind Med. 1990;47: 417-20.
13. Olsson H, Brand L. Occupation exposure to organic solvents and Hodking´s disease in man. Scand J Work Environ Health. 1980;6:302-5.
14. Langman JM. Xylene: its toxicity, measurement of exposure levels, absorption, metabolism and clearance. Pathology. 1994;26:301-9.
15. Chen Z, Liu SJ, Cai SX, Yao YM, Yin H, Ukai H, et al. Exposure of workers to a mixture of toluene and xylenes. II Efects. Occup Environ Med. 1994;51:47-9.
16. Ukai H, Takada S, Inui S, Imai Y, Kawai T, Shimbo S, et al. Occupational exposure to solvent mixtures: effects on health and metabolism. Occup Environ Med. 1994;51:523-9.
17. Yardley-Jones A, Anderson D, Lovell DP, Jenkinson PC. Analysis of chromosomal aberrations in workers exposed to low level benzene. Br J Ind Med. 1990;47:48-51.
18. Eastmond DA, Tucker JD. Identification of aneuploidy-inducing agents using citokinesis-blocked human lymphocytes and an antikinetochore antibody. Environ Mol Mutagen. 1989;13:34-43.
19. Major J, Jakab M, Kiss G, Tompa A. Chromosome aberration, sister-chromatid exchange, proliferative rate index, and serum thiocyanate concentration in smokers exposed to low-dose benzene. Environ Mol Mutagen. 1994;23:137-42.
20. van Damme K, Casteleyn L, Heseltine E, Huici A, Sorsa M, van Larebeke N, et al. Individual susceptibility and prevention of occupational diseases: scientific and ethical issues. J Occup Environ Med. 1995;37:91-9.
21. McKelvey-Martin VJ, Green MH, Schmezer P, Pool-Zobel BL, De Méo MP, Collins A. The single cell gel electrophoresis assay (comet assay): an European review. Mutat Res. 1993;288:47-63.
22. Anderson D, Yu TW, Schmezer P. The effect of various antioxidants and the other modifying agents on oxygen-radical-generated DNA damage in human lymphocytes in the comet assay. Mutat Res. 1994; 307:261-71.
23. Collins A, Dusinská M, Franklin M, Somorovská M, Petrovská H, Duthie S, et al. Comet assay in human biomonitoring studies. Reliability, validation and applications. Environ Mol Mutagen. 1997;30:139-46.
24. Hartmann A, Speit G. Genotoxic effects of chemicals in the single cell gel (SCG) test with human blood cell in relation to the induction of sister chromatid exchanges (SCE). Mutat Res. 1995;346:49-56.
25. Pfuhler S, Wolf HU. Detection of DNA-crosslinking agents with the alkaline comet assay. Environ Mol Mutagen.1996;27:196-201.
26. Fairbairn DW, Olive PL, O´Neill KL. The comet assay: a comprehensive review. Mutat Res. 1995;339:37-59.
27. Collins AR, Duthie SJ, Dobson VL. Direct enzymic detection of endogenous oxidative base damage in human lymphocyte DNA. Carcinogenesis. 1993; 14:1733-5.
28. Hartmann A, Speit G. Comparative investigations of genotoxic effects of metals in the single cell gel (SCG) assay and the sister chromatid exchange (SCE) test. Environ Mol Mutagen. 1994;23:299-305.
29. Speit G, Hanelt S, Helbig R, Seidel A, Hartmann A. Detection of DNA effects in human cells with the comet assay and their relevance for mutagenesis. Toxicol Lett. 1996;88:91-8.
30. Plappert U, Barthel E, Seidel HJ. Reduction of benzene toxicity by toluene. Environ Mol Mutagen. 1994;24:283-92.
31. Pool-Zobel BL Lotzmann N, Knoll M, Kuchenmeister F, Lambertz R, Leucht U, Schröder HG, et al. Detection of genotoxic effects in human gastric and nasal mucosa cells isolated from biopsy samples. Environ Mol Mutagen. 1994;24:23-45.
32. Fuscoe JC, Afshari A, George M, De Angelo AB, Tice RR, SalmanT, et al. In vivo genotoxicity of dichloroacetic acid: Evaluation with the mouse peripheral blood micronucleus assay and the single cell gel assay. Environ Mol Mutagen. 1996;27:1-9.
33. Betti C, Davini T, Giannessi L, Loprieno N, Barale R. Microgel electrophoresis assay (comet test) and SCE analysis in human lymphocytes from 100 normal subjects. Mutat Res. 1994;307:323-33.
34. Green MH, Lowe JE, Waugh AP, Aldridge KE, Cole J, Arlett CF. Effect of diet and vitamin c on DNA strand breakage in freshly-isolated human blood cells. Mutat Res. 1994;316:91-102.
35. Tice RR. The single cell gel/comet: A microgel electrophoretic technique for the detection of DNA damage and repair in individual cell. En: Phillips DH, Venitt S, editors. Environmental mutagenesis. Oxford: Bios Scientific; 1995. p.315-39.
36. Dennong C, Hartmann A, Frey G, Speit G. Detection of DNA damage after hyperbaric oxygen (HBO) therapy. Mutagenesis. 1996;11:605-9.
37. Tice RR, Strauss GH, Peters WP. High-dose combination alkylating agents with autologous bone-marrow support in patients with breast cancer: preliminary assessment of DNA damage in individual peripheral blood lymphocytes using the single cell gel electrophoresis assay. Mutat Res. 1992;271:101-13.
38. GediK CM, Ewen SW, Collins AR. Single-cell electrophoresis applied to the analysis of UV-C damage and its repair in human cell. Int J Radiat Biol. 1992;62:313-20.
39. Green MH, Lowe JE, Harcourt SA, Akinluyi P, Rowe T, Cole J, et al. Sensitivity of unstimulated and stimulated human lymphocytes from normal and xeroderma pigmentosum donors in the comet assay. A potential diagnostic technique. Mutat Res. 1992;273:137-44.
40. Vijayalaxmi, Tice RR, Strauss GH. Assessment of radiation-induced DNA damage in human blood lymphocytes using the single-cell gel electrophoresis technique. Mutat Res. 1992; 271:243-52.
41. Matthias C, Bockmuhl U, Jahnke V, Jones P, Hayes J, Alldersea J, et al. Polymorphism in cytochrome P450 CYP2D6, CYP1A1, CYP2E1 an glutathione S-transferase, GSTM1, GSTM3, GSTT1 and susceptibility to tobacco-related cancers: studies in upper aerodigestive tract cancers. Pharmacogenetics. 1998;8:91-110.
42. Tomatis L, Aitio A, Wilbourn J, Shuker L. Human carcinogens so far identified. Jpn J Cancer Res. 1989;80:795-807.
43. Sing NP, McCoy MT, Tice RR, Schneider EL. A simple technique for quantization of low levels of DNA damage in individual cells. Exp Cell Res.1988;175:184-91.
44. Hayashi SI, Watanabe J, Kawajiri K. Genetic polymorphism in the 5-flanking region change the transcriptional regulation of the human CYP2E1 gene. J Biochem (Tokyo). 1991;110:559-65.
45. Hirvonen A, Husgafvel-Pursiainen K, Antilla S, Karjallainen A, Vainio H. The human CYP2E1 gene and lung cancer: Dra1 and Rsa1 restriction fragment length polymorphism in a Finnish study population. Carcinogenesis. 1993;14:85-8.
46. The National Institute for Occupational Safety and Health (NIOSH). Hippuric and methyl hippuric acids in urine. Method 8301, issue 3. Date: 15 March 2003. [Consultado: 5 de diciembre de 2005]. Disponible en: http://www.cdc.gov/Niosh/nmam/pdfs/8301.pdf
47. Acosta H. Determinación de fenol y ácidos hipúrico y metil hipúrico en orina mediante técnicas cromatográficas (GC-FID y HPLC-UV). Manual de procedimientos. Bogotá: Instituto Nacional de Salud; 1996.
48. Axency for Toxic Substances and Disease Registry.Xileno. CAS #1330-20-7. September 2005. Consultado: 5 de diciembre de 2005. Disponible en: http://www.atsdr.cdc.gov/es/toxfaqs/es_tfacts71.pdf
49. Instituto Nacional de Seguridad e Higiene en el Trabajo.Tabla 5 - Valores límite biológicos, VLBs. Consultado: 5 de diciembre de 2005. Disponible en: http://www.mtas.es/insht/practice/vlb.htm
50. Gonzalez C, Sala N, Capella G. Minireview. Genetic susceptibility and gastric cancer risk. Int J Cancer. 2002;100: 249-60.
51. Torres M, Acosta C, Sicard D, Groot H. Susceptibilidad genética y riesgo de cáncer gástrico en una población del Cauca. Biomédica. 2004;24:153-62.
52. Au W, Lee E, Christiani DC. Biomarker research in occupational health. J Occup Environ Med. 2005;47:145-53.
How to Cite
1.
Torres CH, Varona ME, Lancheros A, Patiño RI, Groot H. DNA damage assessment and biological monitoring of occupational exposure to organic solvents, 2006. Biomed. [Internet]. 2008 Mar. 1 [cited 2025 Apr. 4];28(1):126-38. Available from: https://revistabiomedicaorg.biteca.online/index.php/biomedica/article/view/115
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2008-03-01
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