Biological effect monitoring in industrial workers from the Czech Republic exposed to low levels of butadiene

Tates, A.D.; Dam, F.J. van; Zwart, F.A. de; Darroudi, F.; Natarajan, A.T.; Rössner, Pavel; Peterková, Kateřina; Peltonen, Kimmo; Demopoulos, N.A.; Stephanou, G.; Vlachodimitropoulos, Dimitrios; Srám, Radim J.

doi:10.1016/0300-483x(96)03432-4

Cited by 69 publications

(21 citation statements)

References 18 publications

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“…We also found no increase in HPRT gene mutant frequency among the BD-exposed workers. These negative findings agree with recent reports from studies in the Czech Republic [15], which used classical methods and FISH to examine chromosomal changes, but not with some of the earlier literature [11,14].…”

Section: Discussionsupporting

confidence: 87%

“…Another study by this same group, using the HPRT cloning assay, was positive according to the authors and the mutational spectrum data were compatible with the HPRT mutations being induced by BD, in which an excess of deletions were found [28]. By contrast, our studies in BD-exposed Chinese workers [7] and those in Czech workers by other groups [11,15], using the cloning assay, have failed to find increases in HPRT mutations even though the level of BD exposure was similar to the Texas studies. Furthermore, no increases in chromosome aberrations were found in the Texas facilities, although a "Challenge Assay," in which cells were exposed to gamma rays in G1 in vitro, was positive [29].…”

Section: Discussionsupporting

confidence: 78%

“…To provide mechanistic information on the potential carcinogenicity of BD in humans, we [7][8][9] and others [10][11][12][13][14][15] have investigated genotoxic effects in BD-exposed workers. In a study at a polybutadiene production facility in China, we examined a broad spectrum of genotoxic and other potential effects of BD.…”

Section: Introductionmentioning

confidence: 99%

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Lack of increased genetic damage in 1,3-butadiene-exposed Chinese workers studied in relation to EPHX1 and GST genotypes

Zhang

Hayes

Guo

et al. 2004

Mutation Research/Genetic Toxicology and Environmental Mutagene

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Abstract1,3-Butadiene (BD) is an important industrial chemical and pollutant. Its ability to induce genetic damage and cause hematological malignancies in humans is controversial. We have examined chromosome damage by fluorescence in situ hybridization (FISH) and mutations in the HPRT gene in the blood of Chinese workers exposed to BD. Peripheral blood samples were collected and cultured from 39 workers exposed to BD (median level 2 ppm, 6 h time-weighted average) and 38 matched controls in Yanshan, China. No difference in the level of aneuploidy or structural changes in chromosomes 1, 7, 8, and 12 was detected in metaphase cells from exposed subjects in comparison with matched controls, nor was there an increase in the frequency of HPRT mutations in the BDexposed workers. Because genetic polymorphisms in glutathione S-transferase (GST) enzymes and microsomal epoxide hydrolase (EPHX1) may affect the genotoxic effects of BD and its metabolites, we also related chromosome alterations and gene mutations to GSTT1, GSTM1 and EPHX1 genotypes. Overall, there was no effect of variants in these genotypes on numerical or structural changes in chromosomes 1, 7, 8 and 12 or on HPRT mutant frequency in relation to BD exposure, but the GST genotypes did influence background levels of both hyperdiploidy and HPRT mutant frequency. In conclusion, our data show no increase in chromosomal aberrations or HPRT mutations among workers exposed to BD, even in potentially susceptible genetic subgroups. The study is, however, quite small and the levels of BD exposure are not extremely high, but our findings in China do support those from a similar study conducted in the Czech Republic. Together, these studies suggest that low levels of occupational BD exposure do not pose a significant risk of genetic damage.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionsupporting

confidence: 78%

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Lack of increased genetic damage in 1,3-butadiene-exposed Chinese workers studied in relation to EPHX1 and GST genotypes

Zhang

Hayes

Guo

et al. 2004

Mutation Research/Genetic Toxicology and Environmental Mutagene

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“…The Mfs in both the exposed and control groups averaged 15-20 × 10 -6 , which is much higher than the Mfs for the unexposed control group in our cloning assay study (35). Tates et al (43) studied workers in a butadiene monomer production unit near Prague in the Czech Republic. The median BD exposure, measured in 1994 for 19 workers, was 0.24 ppm, which is less than the median for the high-exposure workers in the present study.…”

Section: Discussionmentioning

confidence: 59%

Assessment of 1,3-Butadiene Exposure in Polymer Production Workers Using HPRT Mutations in Lymphocytes as a Biomarker

Ammenheuser¹,

Bechtold²,

Abdel‐Rahman³

et al. 2001

Environmental Health Perspectives

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“…Elevated hprt variant frequencies correlated well with the amount of the urinary metabolite of BD. In contrast, Tates et al (18) did not find increased hprt mutant frequencies in BD-exposed workers. No cytogenetic effects were detected in a study that involved workers exposed to <3 ppm BD (19).…”

Section: Introductionmentioning

confidence: 87%

Molecular Dosimetry of N-7 Guanine Adduct Formation in Mice and Rats Exposed to 1,3-Butadiene

Koç

Tretyakova

Walker

et al. 1999

Chem. Res. Toxicol.

126

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1,3-Butadiene (BD) is a high-volume chemical used in the production of rubber and plastic. BD is a potent carcinogen in mice and a much weaker carcinogen in rats, and has been classified as a probable human carcinogen. Upon metabolic activation in vivo, it forms DNA-reactive metabolites, 1,2-epoxy-3-butene (EB), 1,2:3, 4-diepoxybutane (DEB), and 3,4-epoxy-1,2-butanediol (EBD). The molecular dosimetry of N-7 guanine adduct formation by these metabolites of BD in liver, lung, and kidney of B6C3F1 mice and F344 rats exposed to 0, 20, 62.5, or 625 ppm BD was studied. The adducts, racemic and meso forms of N-7-(2,3,4-trihydroxybut-1-yl)guanine (THB-Gua), N-7-(2-hydroxy-3-buten-1-yl)guanine (EB-Gua I), and N-7-(1-hydroxy-3-buten-2-yl)guanine (EB-Gua II), were isolated from DNA by neutral thermal hydrolysis, desalted on solid-phase extraction cartridges, and quantitated by LC/ESI(+)/MS/MS. The number of adducts per 10(6) normal guanine bases for a given adduct was higher in mice than rats exposed to 625 ppm BD, but generally similar at lower levels of exposure. The THB-Gua adducts were the most abundant (6-27 times higher than EB-Gua) and exhibited a nonlinear exposure-response relationship. In rats, the exposure-response curves for the formation of THB-Gua adducts reached a plateau after 62.5 ppm, suggesting saturation of metabolic activation. The number of THB-Gua adducts continued to increase in mice between 62.5 and 625 ppm BD. In contrast, the less common EB-Gua adducts had a linear exposure-response relationship in both species. Combining the information from this study with previous data on BD metabolism, we were able to estimate the number of THB-Gua that resulted from DEB and EBD, and conclude that most of the THB-Gua is formed from EBD. We hypothesize that most of the EBD arises from the immediate conversion of DEB to EBD within the endoplasmic reticulum. This study highlights the need for measurements of the levels of EBD in tissues of rats and mice and for the development of a unique biomarker for DEB that is available for binding to DNA.

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Biological effect monitoring in industrial workers from the Czech Republic exposed to low levels of butadiene

Cited by 69 publications

References 18 publications

Lack of increased genetic damage in 1,3-butadiene-exposed Chinese workers studied in relation to EPHX1 and GST genotypes

Lack of increased genetic damage in 1,3-butadiene-exposed Chinese workers studied in relation to EPHX1 and GST genotypes

Assessment of 1,3-Butadiene Exposure in Polymer Production Workers Using HPRT Mutations in Lymphocytes as a Biomarker

Molecular Dosimetry of N-7 Guanine Adduct Formation in Mice and Rats Exposed to 1,3-Butadiene

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