Research and regulatory efforts in toxicology are increasingly focused on the development of suitable non-animal methodologies for human health risk assessment. In this work we used human intestinal Caco-2 and HT29/MTX cell lines to address the potential risks of mixtures of the emerging contaminants tetrabromobisphenol A (TBBPA) and commercial polystyrene nanoparticles (PSNPs). We employed different in vitro settings to evaluate basal cytotoxicity through three complementary endpoints (metabolic activity, plasmatic, and lysosomal membrane integrity) and the induction of the oxidative stress and DNA damage responses with specific endpoints.
View Article and Find Full Text PDFThe potential interactions between the diverse pollutants that can be released into the environment and the resulting outcomes are a challenging issue that needs to be further examined. This in vitro study was aimed to assess potential toxic effects caused by combined exposure to tetrabromobisphenol A, a flame retardant widely used and frequently detected in aquatic matrices, and commercially available polystyrene nanoparticles as reference material to evaluate nanoplastics risks. Our results, using freshwater fish cell lines and a set of relevant cytotoxicity endpoints including cell viability, oxidative stress, and DNA damage, provide additional mechanistic insights that could help to fully characterize the toxicity profiles of tetrabromobisphenol A and polystyrene nanoparticles.
View Article and Find Full Text PDFDNA primase-polymerases (Ppol) have been shown to play active roles in DNA repair and damage tolerance, both in prokaryotes and eukaryotes. The ancestral thermophilic bacterium strain HB27 encodes a Ppol protein among the genes present in mobile element ICETh2, absent in other strains. Using different strategies we ablated the function of Ppol in HB27 cells, either by knocking out the gene through insertional mutagenesis, markerless deletion or through abolition of its catalytic activity.
View Article and Find Full Text PDFExposure to genotoxic stress promotes cell cycle arrest and DNA repair or apoptosis. These "life" or "death" cell fate decisions often rely on the activity of the tumor suppressor gene p53. Therefore, the precise regulation of p53 is essential to maintain tissue homeostasis and to prevent cancer development.
View Article and Find Full Text PDFHealth and environmental risks regarding perfluorooctanoic acid, a well-known perfluorinated compound, are still a subject of great concern. Ubiquitous exposure and disparity of results make it difficult to determine the underlying mechanism of action, especially at the cellular level. This study proposes an experimental design to assess the reversibility of adverse effects after a one-time exposure to the compound, in comparison with other more conventional timings.
View Article and Find Full Text PDFPerfluorooctanoic acid has been used widespread, during the last decades, in a number of consumer and industrial products. Although this compound has been subjected to extensive epidemiological and toxicological studies, limited data are available concerning its potential dermal toxicity in mammalian cells. In this study, we used a two-stage approach with relevant cytotoxicity endpoints including cell viability and proliferation, oxidative stress, DNA damage and cell senescence to assess the immediate and the long-lasting or delayed cytotoxicity caused by the compound in HaCaT keratinocytes.
View Article and Find Full Text PDFDi (2-ethylhexyl) phthalate is a high-production chemical widely used as a plasticizer for polyvinyl chloride products. Due to its ubiquitous presence in environmental compartments and the constant exposure of the general population through ingestion, inhalation, and dermal absorption, this compound has been subjected to extensive in vivo and in vitro toxicological studies. Despite the available information, research on the cytotoxicity of di (2-ethylhexyl) phthalate in mammalian cells is relatively limited.
View Article and Find Full Text PDFButylated hydroxyanisole and propylparaben are phenolic preservatives commonly used in food, pharmaceutical and personal care products. Both chemicals have been subjected to extensive toxicological studies, due to the growing concern regarding their possible impacts on environmental and human health. However, the cytotoxicity and underlying mechanisms of co-exposure to these compounds have not been explored.
View Article and Find Full Text PDFA wide range of cationic amphiphilic drugs (CADs) from different therapeutic areas are known to cause phospholipidosis both in vivo and in vitro. Although the relevance of this storage disorder for human health remains uncertain, CADs have been repeatedly associated with clinical side effects, and as a result, phospholipidosis is of major concern for drug development in the pharmaceutical industry. An important unresolved question in this field is whether phospholipidosis is really linked to cellular toxicity.
View Article and Find Full Text PDFPropyl p-hydroxybenzoate, commonly referred to as propylparaben, is the most frequently used preservative to inhibit microbial growth and extend shelf life of a range of consumer products. The objective of this study was to provide further insight into the toxicological profile of this compound, because of the current discrepancy in the literature with regard to the safety of parabens. The Vero cell line, derived from the kidney of the green monkey, was selected to evaluate the adverse effects of propylparaben by use of a set of mechanistically relevant endpoints for detecting cytotoxicity and genotoxic activities.
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