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Objective This study tested for an association between early cancer-related biomarkers and low-to-moderate exposure to fumes from welding mild steel. Methods Male, non-smoking participants from southern Sweden were recruited and examined (N=338, 171 welders and 167 controls); of these, 78 welders and 96 controls were examined on two occasions six years apart. Exposure to welding fumes was evaluated by measuring respirable dust, welding years, and cumulative exposure. DNA methylation of CpG sites within the cancer-related genes AHRR, F2RL3, and B3GNTL1 was measured by pyrosequencing and relative mitochondrial DNA copy number and telomere length were measured by qPCR in whole-blood samples. Multivariate models were used for longitudinal analysis. Results Median exposure to respirable dust was 0.7 mg/m3 at both timepoints, adjusted for use of personal protective equipment. Compared with controls, welders showed a significant decrease over time in DNA methylation of B3GNTL1 CpG1 and CpG4 [adjusted for age, body mass index, and smoking: β=-0.66, standard error (SE)=0.28; β=-0.48, SE=0.24, respectively]. In addition, exposure to respirable dust and cumulative exposure was associated with a decrease in methylation of F2RL3 CpG2 among all welders (adjusted β=-0.67, SE=0.23 and β=-0.03, SE=0.02, respectively). No significant associations were found for AHRR, mitochondrial DNA copy number, or telomere length. Conclusion Low-to-moderate exposure to welding fumes was associated with a small effect on selected early epigenetic biomarkers of cancer. The direction of the methylation pattern (lower methylation of specific CpG sites) indicates early lung cancer-related changes associated with mild steel welding. [ABSTRACT FROM AUTHOR]

Hormone signaling plays an essential role during fetal life and is vital for brain development. Endocrine-disrupting chemicals can interfere with the hormonal milieu during this critical time-period, disrupting key neurodevelopmental processes. Hence, there is a need for the development of assays that evaluate developmental neurotoxicity (DNT) induced by an endocrine mode of action. Herein, we evaluated the applicability of the neural progenitor C17. 2 cell-line, as an in vitro test system to aid in the detection of endocrine disruption (ED) induced DNT. For this, C17.2 cells were exposed during 10 days of differentiation to agonists and antagonists of the thyroid hormone (Thr), glucocorticoid (Gr), retinoic acid (Rar), retinoic x (Rxr), oxysterols (Lxr), estrogen (Er), androgen (Ar), and peroxisome proliferator activated delta (Pparβ/δ) receptors, as well as to the agonist of the vitamin D (Vdr) receptor. Upon exposure and differentiation, neuronal morphology (neurite outgrowth and branching), and the percentage of neurons in culture were assessed by immunofluorescence. For this, the cells were incubated with Hoechst (nuclear staining) and stained for βIII-tubulin (neuronal marker). The C17.2 cells were responsive to the Rar, Rxr and Pparβ/δ agonists which decreased neurite outgrowth and branching. Additionally, exposure to the Gr agonist increased the number of cells differentiating into neurons, while exposure to the Rxr agonist had the opposite effect. With this approach, we have identified that the C17.2 cells are responsive to Gr, Rar, Rxr, and Pparβ/δ agonists, hence contributing to the development of test systems for hazard assessment of ED-induced DNT.

Objectives: Construction workers are exposed to respirable dust, including respirable crystalline silica (RCS), which is a potential risk factor for cardiovascular disease (CVD). The aim of this study was to evaluate whether exposure to particles among construction workers is associated with short- and long-term alterations in CVD-related serum proteins., Methods: Using proximity extension assay, we measured 92 serum proteins linked to CVD among active male construction workers (N=65, non-smokers) sampled on two occasions: during work and after vacation. First, we used linear models to identify short-term changes in proteins associated with particle exposure (assessed as respirable dust and RCS) during work. Secondly, we used linear mixed models to evaluate whether these associations were long-term, ie, persistent after vacation., Results: The median exposure to respirable dust and RCS during work were 0.25 mg/m3 and 0.01 mg/m3, respectively. Respirable dust was associated with short-term changes in six proteins (tissue factor, growth hormone, heme oxygenase-1, dickkopf-related protein-1, platelet-derived growth factor-B, stem cell factor); long-term associations were observed for the former three proteins. RCS was associated with short-term changes in five proteins (carcinoembryonic antigen-related cell adhesion molecule-8, hydroxyacid oxidase-1, tissue factor, carbonic anhydrase-5A, lectin-like oxidized LDL receptor-1); long-term associations were observed for the former four proteins., Conclusions: Moderate exposure to particles in the construction industry is associated with both short- and long-term changes in circulating CVD-related proteins. Further studies are needed to evaluate if these changes are predictors of occupationally induced clinical CVD.