Evaluation of DNA damage by the Comet assay in shoe workers exposed to toluene and other organic solvents

Pitarque, Marià; Vaglenov, A.; Nosko, Maria; Hirvonen, Ari; Norppa, Hannu; Creus, A.; Marcos, Ricard

doi:10.1016/s1383-5718(99)00042-x

Cited by 104 publications

(53 citation statements)

References 51 publications

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“…Thus, although it may not be possible to point out a single genotoxic agent at the workplace, benzene in gasoline and MDI may explain some of the findings. A possible indication of the heavy organic solvent exposure of the workers was the consistently lowered blood hemoglobin level, which we also observed in the previous study (14). Anemia and other hematologic abnormalities have been associated with organic solvent exposure in Bulgarian petroleum workers (34).…”

Section: Discussionsupporting

confidence: 80%

“…In plant B, where lymphocyte MN frequencies were followed up over 5 years, all four samplings yielded the same result. Although the shoe factory workers did not show any effects in the frequency of SCEs, HFC, or DNA breakage, as measured earlier by the Comet assay (14), our findings indicate the presence of genotoxic exposure at the workplace. This would appear to act via an aneugenic or clastogenic mechanism that does not involve DNA breakage readily detectable by the Comet assay and that does not efficiently lead to SCE formation.…”

Section: Discussioncontrasting

confidence: 45%

“…In a preliminary study of the genotoxic effects of occupational exposure to organic solvents, using the alkaline Comet assay, we did not detect any increase in DNA damage in cryopreserved peripheral blood mononuclear leukocytes from a group of women employed in the two Bulgarian shoe factories (14).…”

mentioning

confidence: 69%

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Sister chromatid exchanges and micronuclei in peripheral lymphocytes of shoe factory workers exposed to solvents.

Pitarque

Vaglenov

Nosko

et al. 2002

Environ Health Perspect

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We examined sister chromatid exchanges (SCEs) and micronuclei (MN; cytokinesis-block method) in cultured peripheral lymphocytes from 52 female workers of two shoe factories and from 36 unexposed age- and sex-matched referents. The factory workers showed an elevated level of urinary hippuric acid, a biomarker of toluene exposure, and workplace air contained high concentrations of various organic solvents such as toluene, gasoline, acetone, and (in one of the plants only) ethylacetate and methylenediphenyl diisocyanate. The shoe factory workers showed a statistically significant higher frequency of micronucleated binucleate lymphocytes in comparison with the referents. This finding agreed with three preliminary MN determinations (each comprising 27-32 shoe workers and 16-20 controls) performed in one of the plants 2-5 years earlier. The shoe factory workers also had a lower average level of blood hemoglobin than the referents. In contrast, no difference was found between the groups in SCE analysis. Smokers showed significantly higher mean frequencies of SCEs per cell and high frequency cells (HFC) than nonsmokers. Aging was associated with increased MN rates and reduced cell proliferation. Polymorphism of the glutathione S-transferase M1 gene (GSTM1) did not affect the individual level of SCEs; but in smoking shoe workers an effect of the occupational exposure on the frequency of micronucleated cells could be seen only in GSTM1 null subjects. The low prevalence of the glutathione S-transferase T1 (GSTT1) null genotype precluded the evaluation of the influence of GSTT1 polymorphism. Our results show that the shoe factory workers have experienced genotoxic exposure, which is manifest as an increase in the frequency of MN, but not of SCEs, in peripheral lymphocytes. The exposures responsible for the MN induction could not be identified with certainty, but exposure to benzene in gasoline and methylenediphenyl diisocyanate may explain some of the findings.

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Section: Discussionsupporting

confidence: 80%

Section: Discussioncontrasting

confidence: 45%

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Sister chromatid exchanges and micronuclei in peripheral lymphocytes of shoe factory workers exposed to solvents.

Pitarque

Vaglenov

Nosko

et al. 2002

Environ Health Perspect

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“…Genetic polymorphisms of CYP2E1, GSTM1, and PONaffected the frequency of CAs using a challenge assay (41). No effects of GSTM1, NAT2, and/or CYPJAJ were observed with exposure to PAHs in coke ovens (6)(7)(8)(9)(10)(11)(12)(13)(14) and oil well fires (20), to organic solvents (34) or to pesticides (44,56).…”

Section: Discussionmentioning

confidence: 99%

Molecular Epidemiology Studies on Occupational and Environmental Exposure to Mutagens and Carcinogens, 1997-1999

Srám¹,

Binková²

2000

Environmental Health Perspectives

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Molecular epidemiology is a new and evolving area of research, combining laboratory measurement of internal dose, biologically effective dose, biologic effects, and influence of individual susceptibility with epidemiologic methodologies. Biomarkers evaluated were selected according to basic scheme: biomarkers of exposure-metabolites in urine, DNA adducts, protein adducts, and Comet assay parameters; biomarkers of effect-chromosomal aberrations, sister chromatid exchanges, micronuclei, mutations in the hypoxanthine-guanine phosphoribosyltransferase gene, and the activation of oncogenes coding for p53 or p21 proteins as measured on protein levels; biomarkers of susceptibility-genetic polymorphisms of genes CYP1A1, GSTM1, GSTT1, NAT2. DNA adducts measured by 32P-postlabeling are the biomarker of choice for the evaluation of exposure to polycyclic aromatic hydrocarbons. Protein adducts are useful as a biomarker for exposure to tobacco smoke (4-aminobiphenyl) or to smaller molecules such as acrylonitrile or 1,3-butadiene. Of the biomarkers of effect, the most common are cytogenetic end points. Epidemiologic studies support the use of chromosomal breakage as a relevant biomarker of cancer risk. The use of the Comet assay and methods analyzing oxidative DNA damage needs reliable validation for human biomonitoring. Until now there have not been sufficient data to interpret the relationship between genotypes, biomarkers of exposure, and biomarkers of effect for assessing the risk of human exposure to mutagens and carcinogens. Key words: air pollution, benzene, biomarkers, coke oven, genotypes, occupational exposure, PAHs, pesticides, tobacco smoke. -Envwron Health Perspect 1 08(suppl 1):57-70 (2000). http.//ehpnetl. niehs. nih.gov/docs/2000/suppl-1/57-70sram/abstract. html A new and evolving area of research termed molecular epidemiology attempts to merge sophisticated and highly sensitive laboratory methods (many of them developed during the recent revolution in molecular biology) with analytical epidemiologic methods. Molecular epidemiology bridges basic research in molecular biology and studies of human cancer causation by combining laboratory measurement of internal dose, biologically effective dose, biologic effects, and the influence of individual susceptibility with epidemiologic methodologies (1). The most common view is that the approach represents a natural convergence of molecular biology and epidemiology (2).The number of biomarkers available for evaluating genetic and cancer risk in humans is quite large. Their utility-for human biomonitoring is suggested by the well-known paradigm of environmentally induced cancer, which represents end points for assessing the entire spectrum of human-genotoxicant interactions (3). These biomarkers begin with exposure and include absorption, metabolism, distribution, critical target interaction (i.e., DNA damage and repair), genetic changes, and finally, disease, which is the province of traditional epidemiology. The development of biomarkers has given rise to the field of ...

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“…In a publication about female workers in two shoe factories with exposure to a complex mixture of various solvents including MDI, an increase in micronuclei in the lymphocytes was described, but no increase in SCE (Pitarque et al 2002). In a second publication by the same research group, no DNA damage in monocytes was detected using the comet assay (Pitarque et al 1999).…”

Section: Genotoxicitymentioning

confidence: 99%

4,4′‐Methylene diphenyl diisocyanate (MDI) [101‐68‐8] and “polymeric” MDI (PMDI) [9016‐87‐9] [MAK Value Documentation, 2008]

2015

The MAK‐Collection for Occupational Health and Safety

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The article contains sections titled: Toxic Effects and Mode of Action Mechanism of Action Toxicokinetics and Metabolism Absorption, distribution, elimination Metabolism Binding to macromolecules/biological monitoring Effects in Humans Single exposures Repeated exposure Local effects on skin and mucous membranes Allergenic effects Reproductive and developmental toxicity Genotoxicity Carcinogenicity Animal Experiments and in vitro Studies Acute toxicity Subacute, subchronic and chronic toxicity Local effects on skin and mucous membranes Allergenic effects Reproductive toxicity Genotoxicity Carcinogenicity Manifesto (MAK value, classification)

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Evaluation of DNA damage by the Comet assay in shoe workers exposed to toluene and other organic solvents

Cited by 104 publications

References 51 publications

Sister chromatid exchanges and micronuclei in peripheral lymphocytes of shoe factory workers exposed to solvents.

Sister chromatid exchanges and micronuclei in peripheral lymphocytes of shoe factory workers exposed to solvents.

Molecular Epidemiology Studies on Occupational and Environmental Exposure to Mutagens and Carcinogens, 1997-1999

4,4′‐Methylene diphenyl diisocyanate (MDI) [101‐68‐8] and “polymeric” MDI (PMDI) [9016‐87‐9] [MAK Value Documentation, 2008]

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