Mutation Research/Genetic Toxicology and Environmental Mutagenesis
Inflammatory response and genotoxicity of seven wood dusts in the human epithelial cell line A549
Introduction
Wood dust is one of the most common occupational dust exposures. Worldwide, approximately 13 million people were occupied in the forestry sector and about 3.5 million people in the furniture industry in year 2000. This means that about 0.4% of the total labour force were occupied in the forestry sector [1]. Recently, Kauppinen et al. [2] reported that 3.6 million workers, i.e. 2.0% of the workforce, were occupationally exposed to wood dusts in the European Union.
Many countries differentiate the regulation between exposures to hardwoods and softwoods (see, e.g. the European Union Directive 1999/38). Hardwoods are usually defined as woods of broad-leaved trees, whereas softwoods are conifers. This categorization is based on the botanical classification system rather than on the physical and chemical properties of the wood species.
Cancer in the sino-nasal cavities is rare, with a worldwide annual standardized incidence rate of 1.05/100,000 persons for men and 0.45 for women [3]. Cancer at this site has been strongly associated with different occupational exposures [4], including exposure to wood dust. Several independent studies have found excess risks among employees working in wood-related industries [5], [6], [7]. When classifying the cancers by histology, adeno-carcinomas are even more strongly associated with wood dust exposure. In a meta-analysis of 12 case–control studies, an odds ratio of 45.5 (28.3–72.9) was calculated for male workers in jobs with high levels of wood dust exposure [5].
In 1995, the International Agency for Research of Cancer [8] evaluated wood dust as being carcinogenic to humans (Group 1). The conclusion was based on a substantial amount of epidemiological evidence, despite the sparse knowledge about the underlying mechanisms and pathways. The studies showed the strongest correlation between nasal cancer and exposure to dust from hardwood, especially oak and beech [9]. However, sino-nasal cancer among employees who worked with other wood types and species has also been reported [8].
In addition to cancer, wood dust exposure is also associated with non-malignant health effects like impaired lung function, occupational asthma, rhinitis and allergic contact dermatitis [10], [11], [12], [13], [14], [15]. We therefore tested whether an indirect pathway involving inflammation and oxidative stress was related to DNA strand break formation, which is a potential indicator of a carcinogenic mechanism [16].
This study was aimed at investigating whether the inflammatory response and the genotoxicity of dusts from common woods differ. Animal models for studying the carcinogenic effects of wood dusts are lacking. Therefore, in vitro data may be an important tool for suggesting preventive measures, such as distinguishing between the toxicity of certain wood types. Dusts made from six wood species and dust from medium density fibreboard (MDF) was tested to encompass common wood materials (i.e. hard, soft, exotic and artificial wood). Beech, birch and oak were selected because of their widespread use in the furniture industry. Teak is a popular exotic hardwood in furniture making. Pine and spruce represent softwoods, and MDF is a manufactured wood material that is commonly used in furniture and for construction.
Section snippets
Wood dust
Well-characterized wood dusts from beech, birch, MDF, oak, pine, spruce and teak were produced by the Kupio Regional Institute of Occupational Health (Kuopio, Finland) according to methods described by Naarala et al. [17]. Good-quality raw materials were selected that had not been impregnated with wood preservatives. The production and characteristics of the wood dusts have been described by Long et al. [18] and Maatta et al. [19], [20], except for the MDF dust. The MDF dust was produced by the
Cytotoxicity
Cytotoxicity was assessed by measuring the secretion of lactate dehydrogenase into the medium as the fraction of the activity in lysates of Triton-X-lysed cells. In the initial set-up, we measured the LDH content in the media after 3, 6, 24 and 48 h of exposure, and found that the wood dusts were strongly toxic after 24 and 48 h of incubation (data not shown). After 3 and 6 h of exposure, no substantial toxicity was detected (Table 2). For this reason, we decided to focus the study on the 3 and
Discussion
Several epidemiological studies have shown both malignant and non-malignant health effects after occupational exposure to wood dust, especially after exposure to hardwood dusts [5], [12]. However, in most of the epidemiological studies, the employees have worked with several wood species simultaneously, which makes it difficult to estimate the harmful potential of the different wood species. Another problem is that it has not yet been possible to mimic in experimental animals the human wood
Conclusions
We here report that four out of seven wood dusts induce DNA strand-breaks in cultured A549 cells. DNA strand-breaks occurred before the inflammation had reached its maximum, which suggests that wood dusts are genotoxic without involvement of inflammatory responses. Both hardwood and softwood species caused DNA strand-breaks. Cytokine responses were induced by all seven wood dust species, with the lowest and highest responses found among the hardwoods, and the responses of the softwoods between
Acknowledgements
Technical assistance from Lourdes Pedersen and Yonit Bertelsen and the comments from Dr. Corey Cohn are gratefully acknowledged. This study was supported by EU 5th Framework Programme, Key Action 4, Environment and Health, Quality of Life and Management of Living Resources, project no. QLK4-2000-00573 and the Airpolife center of excellence granted by the Danish Research agency.
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