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

Abstract

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.

The Effects of GSTM1 and GSTT1 Polymorphisms on Micronucleus Frequencies in Human Lymphocytes In vivo

“…The individual data sets included in this pooled analysis revealed that the influence of GST genotype on micronucleus frequencies was statistically significant only in two (17,19) of the eight studies and only for GSTM1. Our finding confirms that pooled analyses, by increasing the statistical power, are adequate for assessing the involvement of genetic variants on genome stability and for resolving discrepancies among individual studies.…”

“…Data on GSTM1, GSTT1 genotypes, and micronucleus frequencies of the same subjects were collected from seven European laboratories. The database included data from articles already published (14)(15)(16)(17)(18)(19)(20), and from an unpublished study done at the University of Pisa, Italy (partially published in refs. 21,22).…”

“…All studies used the cytokinesis-block micronucleus assay in peripheral blood lymphocytes (6). Methods of genotyping were described in the original articles (14)(15)(16)(17)(18)(19)(20)(21)(22). Deviations from the Hardy-Weinberg equilibrium were not tested because heterozygous GSTM1 and GSTT1 individuals could not be distinguished from wild type using PCR followed gel electrophoresis.…”

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

“…Here too, however, evaluation is not possible as a result of inadequate documentation. 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).…”

Dysregulation of markers of oxidative stress and DNA damage among nail technicians despite low exposure to volatile organic compounds

“…Nevertheless, interest in the oxidative damage caused by these solvents' toxic effects have only is relatively new, and thus the amount of evidence concerning their possible genotoxic and carcinogenic potential is scarce and still under discussion. Even though these substances are considered to be neither carcinogenic nor genotoxic to humans (IARC class 3 carcinogens, ie, not classifiable as to their carcinogenicity to humans), there is a growing amount of evidence suggesting increased (i) levels of markers of oxidative stress (10)(11)(12), (ii) rate of chromosomal aberrations or sister chromatid exchange (12)(13)(14), and (iii) incidence of various cancers among workers occupationally exposed to toluene or xylene [even at occupational exposures far below the respective occupational limits (15)(16)(17)(18)(19)(20)(21)]. Although precise mechanisms underlying the effects of toluene and xylene remain unknown, the role of oxidative stress, oxidative DNA damage and dysregulated cellular antioxidant levels have been implicated (22)(23)(24).…”