Mass spectrometry-based metabolomics study of nicotine exposure in THP-1 monocytes.

The tobacco alkaloid nicotine is known for its activation of neuronal nicotinic acetylcholine receptors. Nicotine is consumed in different ways such as through conventional smoking, e-cigarettes, snuff or nicotine pouches. The use of snuff has been associated with several adverse health effects, such as inflammatory reactions of the oral mucosa and oral cavity cancer. We performed a metabolomic analysis of nicotine-exposed THP-1 human monocytes. Cells were exposed to 5 mM of the alkaloid for up to 4 h, and cell extracts and medium subjected to untargeted liquid chromatography high-resolution mass spectrometry. Raw data processing revealed 17 nicotine biotransformation products. Among these, cotinine and nornicotine were identified as the two major cellular biotransformation products. The application of multi- and univariate statistical analyses resulted in the annotation, up to a certain level of identification, of 12 compounds in the cell extracts and 13 compounds in the medium that were altered by nicotine exposure. Of these, four were verified as methylthioadenosine, cytosine, uric acid, and L-glutamate. Methylthioadenosine levels were affected in both cells and the medium, while cytosine, uric acid, and L-glutamate levels were affected in the medium only. The effects of smoking on the pathways involving these metabolites have been previously demonstrated in humans. Most of the other discriminating compounds, which were merely tentatively or not fully identified, were amino acids or amino acid derivatives. In conclusion, our preliminary data suggest that some of the potentially adverse effects related to smoking may also be expected when nicotine is consumed via snuff or nicotine pouches.

In vitro effects of dental monomer exposure - Dependence on the cell culture model.

Methacrylate monomers are major components of resin-based biomaterials. The polymerization of these materials is never complete, and methacrylates leaking from cured materials cause exposure of patients. Only some selected methacrylates have thoroughly been tested for possible interaction with living cells. In the current study, we compared the effects of 2-hydroxyethyl-methacrylate (HEMA; a carefully studied methacrylate) and hydroxypropyl-methacrylate (HPMA; a scarcely investigated methacrylate). Five cell lines differing in both source and cell type were used. The cells were exposed to methacrylates (1-8 mM). Cell viability, cell death, glutathione levels, reactive oxygen species (ROS), and cell growth pattern were measured. Both methacrylates reduced cell viability, and glutathione depletion was observed in all cell lines. The cell death pattern varied among the cell lines. The ROS levels and cell growth pattern also differed between the cell lines after exposure to methacrylate monomers. No difference between HEMA and HPMA exposures were observed in any of the cell lines. The variation between cell lines shows that the measured methacrylate toxicity depends heavily on the test system chosen. Further, the conformity between HEMA and HPMA effects suggests that the two methacrylates similarly affect living cells.