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As part of a large human biomonitoring study, we conducted occupational monitoring in a glass fibre factory inSlovakia. Shopfloor workers (n = 80), with a matched group of administrators in the same factory (n = 36), weremonitored for exposure to glass fibres and to polycyclic aromatic hydrocarbons (PAHs). The impact of occupationalexposure on chromosomal aberrations, DNA damage and DNA repair, immunomodulatory markers, andthe role of nutritional and lifestyle factors, as well as the effect of polymorphisms in metabolic and DNA repairgenes on genetic stability, were investigated. The (enzyme-modified) comet assay was employed to measure DNA strand breaks (SBs) and apurinic sites,oxidised and alkylated bases. Antioxidant status was estimated by resistance to H2O2-induced DNA damage. Baseexcision repair capacity was measured with an in vitro assay (based on the comet assay). Exposure of workers to fibres was low, but still was associated with higher levels of SBs, and SBs plus oxidisedbases, and higher sensitivity to H2O2. Multivariate analysis showed that exposure increased the risk of high levelsof SBs by 20%. DNA damage was influenced by antioxidant enzymes catalase and glutathione S-transferase(measured in blood). DNA repair capacity was inversely correlated with DNA damage and positively withantioxidant status. An inverse correlation was found between DNA base oxidation and the percentage ofeosinophils (involved in the inflammatory response) in peripheral blood of both exposed and reference groups.Genotypes of XRCC1 variants rs3213245 and rs25487 significantly decreased the risk of high levels of baseoxidation, to 0.50 (p = 0.001) and 0.59 (p = 0.001), respectively. Increases in DNA damage owing to glass fibre exposure were significant but modest, and no increases wereseen in chromosome aberrations or micronuclei. However, it is of concern that even low levels of exposure tothese fibres can cause significant genetic damage.

Background B-cell chronic lymphocytic leukemia (CLL) is a common type of adult leukemia. It often follows an indolent course and is preceded by monoclonal B-cell lymphocytosis, an asymptomatic condition, however it is not known what causes subjects with this condition to progress to CLL. Hence the discovery of prediagnostic markers has the potential to improve the identification of subjects likely to develop CLL and may also provide insights into the pathogenesis of the disease of potential clinical relevance. Results We employed peripheral blood buffy coats of 347 apparently healthy subjects, of whom 28 were diagnosed with CLL 2.0–15.7 years after enrollment, to derive for the first time genome-wide DNA methylation, as well as gene and miRNA expression, profiles associated with the risk of future disease. After adjustment for white blood cell composition, we identified 722 differentially methylated CpG sites and 15 differentially expressed genes (Bonferroni-corrected p

The utility of blood-based omic profiles for linking environmental exposures to their potential health effects was evaluated in 649 individuals, drawn from the general population, in relation to tobacco smoking, an exposure with well-characterised health effects. Using disease connectivity analysis, we found that the combination of smoking-modified, genome-wide gene (including miRNA) expression and DNA methylation profiles predicts with remarkable reliability most diseases and conditions independently known to be causally associated with smoking (indicative estimates of sensitivity and positive predictive value 94% and 84%, respectively). Bioinformatics analysis reveals the importance of a small number of smoking-modified, master-regulatory genes and suggest a central role for altered ubiquitination. The smoking-induced gene expression profiles overlap significantly with profiles present in blood cells of patients with lung cancer or coronary heart disease, diseases strongly associated with tobacco smoking. These results provide proof-of-principle support to the suggestion that omic profiling in peripheral blood has the potential of identifying early, disease-related perturbations caused by toxic exposures and may be a useful tool in hazard and risk assessment.