Does occupational exposure to mineral fibres cause DNA or chromosome damage?

doi:10.1016/j.mrfmmm.2004.06.029

Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis

Volume 553, Issues 1–2, 3 September 2004, Pages 103-110

https://doi.org/10.1016/j.mrfmmm.2004.06.029 Get rights and content

Abstract

Markers of genetic stability were monitored in lymphocytes from 98 workers employed in rockwool manufacture in a factory in the Slovak Republic, and 43 controls (administrative employees in the same factory). Strand breaks in lymphocyte DNA were higher in exposed compared to control non-smokers, but there was no effect of exposure on specific damage to bases in DNA, nor on chromosome aberrations. The frequency of micronuclei was higher in women in the control group than in rockwool-exposed women. DNA repair (8-oxoguanine DNA glycosylase activity) was unaffected by exposure, but was negatively correlated with micronucleus frequency, implying that unrepaired 8-oxoguanine contributes to micronucleus formation. The conclusion from this study is that, overall, rockwool exposure has no deleterious effect on genetic stability in humans.

Introduction

The production, sale and use of asbestos are no longer permitted in Europe. Some of the properties of asbestos (e.g. as an insulation material) can be substituted by alternative man-made fibres. Rockwool is a man-made mineral fibre (MMMF) manufactured from rock. Although it was formerly regarded by the International Agency for Research on Cancer (IARC) as a possibly carcinogenic material (in the classification group 2B), it was reassessed in 2001 and is now assigned to Group 3, i.e. not classifiable as to human carcinogenicity [1]. There is only weak epidemiological evidence linking rockwool exposure with human cancer [1]. There appear to have been few studies of the possible genotoxicity of MMMF. In principle, fibres might induce carcinogenesis directly, or via inflammation, with its associated release of reactive oxygen, damage to DNA and cell proliferation; on the other hand, rockwool fibres are cleared rapidly from the rodent lung [2]. In recent in vitro experiments in rat alveolar macrophages, rockwool was not cytotoxic [3].

As part of an EC-funded investigation into the possible consequences to health of exposure to mineral fibres, we have monitored various biomarkers related to genotoxicity in 98 workers exposed to rockwool during its manufacture in a factory in Nova Bana, Slovak Republic and 43 control employees of the same factory working in adminstrative or other jobs with minimal exposure to rockwool. DNA strand breaks were measured in lymphocytes, using the comet assay (single cell alkaline gel electrophoresis). DNA base damage was estimated with lesion-specific endonucleases to convert the damaged bases to breaks. The DNA base excision repair capacity of lymphocytes was assessed using a modified comet assay in which a cell-free extract from the lymphocytes was incubated with a DNA substrate containing oxidised guanine. Micronuclei and chromosome aberrations were analysed in phytohaemagglutinin-stimulated lymphocytes.

Section snippets

Subject selection

Workers with at least 5 years’ exposure to rockwool at an industrial plant in Nova Bana, Slovakia were recruited for this study. The sampling was carried out in September, 2000. An age-matched control group of clerical workers from the same factory was also studied (Table 1). The participants were interviewed by trained personnel and answered detailed questionnaires relating to duration of asbestos exposure, smoking, alcohol consumption and nutritional habits. All workers underwent clinical

Results

The only indication of an effect of exposure to rockwool on DNA damage levels was in strand breaks, which were higher in the exposed workers than in the controls (Table 2). Effects of smoking were apparent in the control group: smokers had higher levels of strand breaks, while FPG- and AlkA-sensitive sites were elevated in non-smokers compared with smokers.

No differences were found in the levels of chromosome aberrations in exposed and control groups, or in smokers compared with non-smokers.

Discussion

There is little indication from our results of any genotoxic effects resulting from exposure to rockwool fibres. The only positive effect is on the level of DNA strand breaks in non-smokers. Strand breaks, although obviously a form of damage, are difficult to interpret. They are induced by a variety of genotoxic agents, and are usually rapidly repaired. They also appear as intemediates in excision repair, so that it is conceivable that an increase in strand breaks actually indicates greater

Acknowledgements

We thank all participants in the Rockwool factory (Izomat, Nová Ba $n ⌣$ a), as well as the management, for their enthusiastic participation. Sampling and medical investigation was carried out with help of the National Institute of Health, Banská Bystrica. We thank Dr Kornélia Burghardtová and Helena Petrovská for their help with the comet assay and to Mrs Anna Morávková and Anna Gažiová, Renáta Mátéová, Kristı́na Gavaĺová, Zuzana Roštášová, Ĺubica Miklošková and Jarmila Jantošková for their

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Human malignancies are often hallmarked with genomic instability, which itself is also considered a causative event in malignant transformation. Genomic instability may manifest itself as genetic changes in the nucleotide sequence of DNA, or as structural or numerical changes of chromosomes. Unrepaired or insufficiently repaired DNA double-strand breaks, as well as telomere shortening, are important contributors in the formation of structural chromosomal aberrations (CAs). In the present review, we discuss potential mechanisms behind the formation of CAs and their relation to cancer. Based on our own studies, we also illustrate how inherited genetic variation may modify the frequency and types of CAs occurring in humans. Recently, we published a series of studies on variations in genes relevant to maintaining genomic integrity, such as those encoding xenobiotic-metabolising enzymes, DNA repair, the tumour suppressor TP53, the spindle assembly checkpoint, and cyclin D1 (CCND1). While individually genetic variation in these genes exerted small modulating effects, in interactions they were associated with CA frequencies in peripheral blood lymphocytes of healthy volunteers. Moreover, we observed opposite associations between the CCND1 splice site polymorphism rs9344 G870A and the frequency of CAs compared to their association with translocation t(11,14). We discuss the functional consequences of the CCND1 gene in interplay with DNA damage response and DNA repair during malignant transformation.
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Does occupational exposure to mineral fibres cause DNA or chromosome damage?

Abstract

Introduction

Section snippets

Subject selection

Results

Discussion

Acknowledgements

Mutat. Res.

Mutat. Res.

Synthetic vitreous fibres: a review of toxicology research and its impact on hazard classification

Crit. Rev. Toxicol.

Comparative cytotoxicity study of rock wool and chrysotile by cell magnetometric evaluation

Inhal. Toxicol.